☆ 4.7 Review

Chronic inflammation and the hallmarks of aging

MOLECULAR METABOLISM (2023)

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Loss of epigenetic information as a cause of mammalian aging

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Resurrection of endogenous retroviruses during aging reinforces senescence

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DNA damage and repair in age-related inflammation

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Summary: Genomic instability is a key factor in the process of aging, with accumulated DNA damage leading to cell death, senescence, tissue dysfunction, and inflammation. This review explores the link between DNA damage, inflammation, and aging, particularly in the context of premature aging syndromes and age-related diseases. The study highlights the mechanisms by which DNA damage induces inflammation and discusses potential therapeutic targets.

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Summary: Age-associated B cells (ABCs) play critical roles in the pathogenesis of autoimmune disorders, aging-associated diseases, and infections. They exhibit a distinctive phenotype and express T-bet and CD11c markers, hence known as CD11c(+)T-bet(+) B cells. The formation of ABCs is promoted by specific combinations of innate and adaptive signals.

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Telomere Shortening and Its Association with Cell Dysfunction in Lung Diseases

Andy Ruiz et al.

Summary: This article discusses the important role of telomere shortening (TS) in lung diseases. In addition to age, other factors can induce TS and increase the risk of lung diseases. In an infectious environment, immune cells with TS are associated with severe lymphopenia and death, while in a non-infectious context, naive T cells with TS are related to cancer progression and enhanced inflammatory processes.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Dephosphorylation of AMP-activated protein kinase exacerbates ischemia/reperfusion-induced acute kidney injury via mitochondrial dysfunction

Haijian Ma et al.

Summary: This study reveals that AMP-activated protein kinase (AMPK) plays an important protective role in tubular epithelial cells during acute kidney injury. The deficiency of AMPK leads to lipid droplet accumulation and elevated levels of ceramides and free fatty acids in the kidney tubules, resulting in worsened kidney impairment.

KIDNEY INTERNATIONAL (2022)

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FOXP3+ regulatory T cells and age-related diseases

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Summary: Regulatory T (Treg) cells play a critical role in maintaining immune homeostasis and their dysfunction in aged patients may contribute to age-related diseases. Immune therapies targeting Treg cells show promising results in treating cancers and autoimmune diseases. Understanding Treg cell function better may help in developing new immune therapies against aging.

FEBS JOURNAL (2022)

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The landscape of human tissue and cell type specific expression and co-regulation of senescence genes

Peng Xu et al.

Summary: This study analyzed gene network data from healthy human tissues to investigate co-expression signatures of senescence genes (SnGs) and their specificity in different cell types. The research identified highly conserved SnGs across human tissues, with specific enrichment in fibroblasts, endothelial cells, and immune cells. Single-cell RNA-seq and spatial transcriptomic data further confirmed the cell-type specific SnG signatures predicted by the network analysis, providing insights for future studies on senescent cells in human tissues.

MOLECULAR NEURODEGENERATION (2022)

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Review Cell Biology

Telomere dysfunction in ageing and age-related diseases

Francesca Rossiello et al.

Summary: The article reviews the impact of telomere shortening and dysfunction on aging and a variety of age-related diseases in humans. Accumulation of senescent cells in aging organisms is believed to contribute to bodily dysfunction. Telomere shortening and damage are known causes of cellular senescence and aging. The authors argue that telomeric dysfunction plays a broad role in human pathologies associated with normal aging.

NATURE CELL BIOLOGY (2022)

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Review Immunology

Immunogenic cell stress and death

Guido Kroemer et al.

Summary: Immunogenic cell death (ICD) plays an important role in therapy and disease, as dying mammalian cells release signals that interact with the host to determine the immunological correlates of cellular stress and death. ICD is crucial in immunosurveillance and is related to strategies evolved by pathogens and cancer cells. Additionally, normal cell death can also initiate antigen-specific immune responses.

NATURE IMMUNOLOGY (2022)

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Article Cell Biology

PGC-1α inhibits the NLRP3 inflammasome via preserving mitochondrial viability to protect kidney fibrosis

Bo Young Nam et al.

Summary: This study reveals that PGC-1 alpha-induced inactivation of the NLRP3 inflammasome, through modulation of mitochondrial viability and dynamics, can ameliorate kidney injury.

CELL DEATH & DISEASE (2022)

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Review Oncology

Hallmarks of Cancer: New Dimensions

Douglas Hanahan

Summary: The concept of the hallmarks of cancer is a tool for simplifying the complexity of cancer phenotypes and genotypes into basic principles. This article proposes phenotypic plasticity and disrupted differentiation as distinct hallmark capabilities, and discusses nonmutational epigenetic reprogramming and polymorphic microbiomes as enabling characteristics. Additionally, the importance of senescent cells in the tumor microenvironment is highlighted. The integrative concept of the hallmarks of cancer helps in understanding the mechanisms of cancer development and applying that knowledge to cancer medicine.

CANCER DISCOVERY (2022)

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Article Endocrinology & Metabolism

TLR9 regulates NLRP3 inflammasome activation via the NF-kB signaling pathway in diabetic nephropathy

Jinfeng Shen et al.

Summary: The study reveals the significant role of TLR9 in the development of diabetic nephropathy. Inhibition of TLR9 can alleviate inflammation and apoptosis, and improve kidney function. These findings provide new insights for the treatment of DN.

DIABETOLOGY & METABOLIC SYNDROME (2022)

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Article Cell & Tissue Engineering

IL-6 coaxes cellular dedifferentiation as a pro-regenerative intermediate that contributes to pericardial ADSC-induced cardiac repair

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Summary: This study reveals the role of IL-6 in cardiac dedifferentiation and regeneration, providing an innovative strategy for stem cell therapy in ischemic heart disease.

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The mTOR-lysosome axis at the centre of ageing

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Summary: This article discusses the special relationship between the mechanistic target mTORC1 and lysosomes, highlighting how inhibiting mTORC1 and activating the autophagy-lysosome pathway can slow down the molecular hallmarks of aging. It provides strong evidence for targeting the autophagy-lysosome pathway in treatments aimed at slowing biological aging and extending lifespan.

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Circulating Mitochondrial DNA and Inter-Organelle Contact Sites in Aging and Associated Conditions

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Summary: Mitochondria play a crucial role in cell bioenergetics, regulation of redox homeostasis, and cell death/survival signaling. They also have immunostimulatory properties and can release organelles or mitochondrial DNA to activate immune responses. The interactions between mitochondria optimize their activity according to the energy demands of specific cells or tissues, and inter-organelle communication can promote the release of mitochondrial components and trigger systemic inflammation. Age-related chronic inflammation is associated with mitochondrial dysfunction and increased release of mitochondrial components, particularly cell-free mtDNA, highlighting the central role of mitochondria in the aging process and related conditions.

CELLS (2022)

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Review Cell Biology

Noncoding RNAs in age-related cardiovascular diseases

Amela Jusic et al.

Summary: Cardiovascular diseases are the leading cause of morbidity and mortality worldwide, posing a significant economic burden and public health concern. Noncoding transcripts, specifically noncoding RNAs, play vital roles in aging and contribute to the development of cardiovascular diseases. They regulate biological processes related to aging and impact pathophysiological developments within the cardiovascular system.

AGEING RESEARCH REVIEWS (2022)

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Review Cell Biology

Contribution of proteases to the hallmarks of aging and to age-related neurodegeneration

Mamta Rai et al.

Summary: Protein quality control is crucial for cellular homeostasis and health, with proteases playing a key role in this process. Proteases impact aging and age-related neurodegeneration by regulating various cellular functions and pathogenic protein degradation or generation.

AGING CELL (2022)

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Article Cell Biology

Defective mitophagy in aged macrophages promotes mitochondrial DNA cytosolic leakage to activate STING signaling during liver sterile inflammation

Weizhe Zhong et al.

Summary: Aging impairs mitophagy and lysosomal function in macrophages, leading to the cytosolic release of mtDNA and increased STING activation. This promotes sterile inflammatory liver injury in aged patients. The findings suggest potential therapeutic targets for treating aged patients with sterile inflammatory liver injury.

AGING CELL (2022)

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Review Physiology

IMPLICATIONS OF THE NADASE CD38 IN COVID PATHOPHYSIOLOGY

Julianna D. Zeidler et al.

Summary: During the COVID-19 pandemic, it has been observed that the elderly and individuals with age-related syndromes are more susceptible to severe immune responses. CD38 has been implicated in the altered immunometabolism resulting from COVID-19 infection, suggesting it as a potential therapeutic target.

PHYSIOLOGICAL REVIEWS (2022)

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Article Immunology

Mitochondrial electron transport chain is necessary for NLRP3 inflammasome activation

Leah K. Billingham et al.

Summary: The study found that inhibitors of different complexes in the mitochondrial electron transport chain (ETC) can prevent the activation of the NLRP3 inflammasome, and the expression of specific enzymes from yeast or tunicates can rescue the activation of NLRP3 inflammasome in the absence of functional mitochondrial complex I or III. Metabolomics revealed that ATP generation through the phosphocreatine-dependent mechanism sustains the activation of NLRP3 inflammasome.

NATURE IMMUNOLOGY (2022)

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Review Gastroenterology & Hepatology

The gut microbiome as a modulator of healthy ageing

Tarini Shankar Ghosh et al.

Summary: This review explores the relationship between the gut microbiome and aging, as well as unhealthy aging, and the potential for microbiome-directed interventions to promote healthy aging.

NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY (2022)

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Article Multidisciplinary Sciences

NOS2 and S-nitrosothiol signaling induces DNA hypomethylation and LINE-1 retrotransposon expression

Christopher H. Switzer et al.

Summary: Inducible nitric oxide synthase (NOS2) and nitric oxide (NO) signaling lead to DNA hypomethylation and genomic instability through degradation of DNMT1 protein and retrotransposon activation. NOS2 expression levels are correlated with decreased DNA methylation and malignant cellular transformation in breast cancer patients.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2022)

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Article Multidisciplinary Sciences

DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases

Matthias Wielscher et al.

Summary: This study found that chronic inflammation can lead to changes in DNA methylation, which may be a consequence of inflammation and have an impact on disease.

NATURE COMMUNICATIONS (2022)

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Article Multidisciplinary Sciences

Distinct and additive effects of calorie restriction and rapamycin in aging skeletal muscle

Daniel J. Ham et al.

Summary: The anti-aging intervention calorie restriction (CR) is thought to act via the nutrient-sensing multiprotein complex mTORC1. However, this study showed that the mTORC1-inhibitor rapamycin and CR use largely distinct mechanisms to slow mouse muscle aging.

NATURE COMMUNICATIONS (2022)

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Article Multidisciplinary Sciences

Microglial NF-κB drives tau spreading and toxicity in a mouse model of tauopathy

Chao Wang et al.

Summary: The activation of microglial NF-kappa B signaling is crucial for tau spreading and tau-mediated spatial learning and memory deficits in tauopathy mice. Inhibiting NF-kappa B activation reverses tau-associated microglial states and rescues autophagy deficits. This study establishes the role of microglial NF-kappa B signaling in mediating tau spreading and toxicity in tauopathy.

NATURE COMMUNICATIONS (2022)

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Article Biology

Multi-omic rejuvenation of human cells by maturation phase transient reprogramming

Diljeet Gill et al.

Summary: Ageing is a gradual decline in organismal fitness that is associated with reduced cellular function and altered gene expression. Recent research has shown that the epigenome can be rejuvenated during somatic cell reprogramming, suggesting that full reprogramming may not be necessary to reverse ageing. In this study, the researchers developed a method called maturation phase transient reprogramming (MPTR), which selectively expresses reprogramming factors until a rejuvenation point and then withdraws them. They found that this method rejuvenated multiple cellular attributes, including the transcriptome and epigenome, to a larger extent than previous protocols. Overall, this work demonstrates the possibility of separating rejuvenation from complete pluripotency reprogramming and may facilitate the discovery of anti-ageing genes and therapies.

ELIFE (2022)

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Article Geriatrics & Gerontology

Telomerase deficiency reflects age-associated changes in CD4+T cells

Diana M. Matthe et al.

Summary: The research found that in telomerase-deficient mice, there was a reduction in CD4+ T cell numbers and an enhancement in proliferation and Th1 polarization, with increased production of IFN gamma-producing cells and reduced CD28 expression. These results suggest that telomerase deficiency replicates several changes in CD4+ T cells seen in aged humans, highlighting its potential role in T cell immunity aging.

IMMUNITY & AGEING (2022)

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Review Immunology

Myeloid Responses to Extracellular Vesicles in Health and Disease

Priya Makhijani et al.

Summary: Extracellular vesicles play a crucial role in cell-cell communication and modulating myeloid immunity in cancer and autoimmune disease. Understanding the biology of extracellular vesicles can contribute to the development of novel therapeutic and diagnostic applications.

FRONTIERS IN IMMUNOLOGY (2022)

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Review Cell Biology

Proteostasis Perturbations and Their Roles in Causing Sterile Inflammation and Autoinflammatory Diseases

Jonas Johannes Papendorf et al.

Summary: Proteostasis refers to the ability of cells to maintain a stable proteome through protein synthesis, quality control, and degradation. Disorders caused by proteostasis perturbations are increasingly being identified, and they often exhibit an autoinflammatory component. This review provides an overview of the molecular pathogenesis of these disorders and summarizes the mechanisms by which impaired proteostasis promotes autoinflammation.

CELLS (2022)

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Review Immunology

Regulatory T cells as metabolic sensors

Paola de Candia et al.

Summary: Regulatory T cells, as key metabolic sensors, play a crucial role in controlling immune state and have promising therapeutic potential for autoimmune and metabolic disorders.

IMMUNITY (2022)

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Article Biochemistry & Molecular Biology

Immunoproteasome Inhibition Ameliorates Aged Dystrophic Mouse Muscle Environment

Luana Tripodi et al.

Summary: This study demonstrates that ONX-0914, a selective inhibitor of the PSMB8 subunit of immunoproteasome, improves pathological traits associated with muscle wasting in a mouse model of Duchenne muscular dystrophy. It reduces inflammation, increases regulatory T cells, and buffers oxidative stress, ultimately leading to a decrease in fibrosis. This suggests that ONX-0914 could be a promising therapeutic approach for slowing down muscle mass loss in dystrophic patients.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Review Chemistry, Medicinal

Antiaging agents: safe interventions to slow aging and healthy life span extension

Ji-Kai Liu

Summary: Human longevity has increased significantly in the past century, and the exploration of new targets for anti-aging agents provides a great opportunity for the healthcare and pharmaceutical industries.

NATURAL PRODUCTS AND BIOPROSPECTING (2022)

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Article Biochemistry & Molecular Biology

AMPK directly phosphorylates TBK1 to integrate glucose sensing into innate immunity

Qian Zhang et al.

Summary: This study found that viral infection leads to a rapid decrease in blood glucose levels, resulting in the activation of AMPK. The activated AMPK directly phosphorylates TBK1, triggering the recruitment of IRF3 and the assembly of MAVS or STING signalosomes. However, depletion or inhibition of AMPK and increased glucose levels impair nucleic acid sensing, while enhancing the AMPK-TBK1 cascade significantly improves antiviral immunity.

MOLECULAR CELL (2022)

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Article Multidisciplinary Sciences

The phosphorylation of AMPKß1 is critical for increasing autophagy and maintaining mitochondrial homeostasis in response to fatty acids

Eric M. Desjardins et al.

Summary: This study demonstrates the important physiological role of AMPK ss 1 Ser108 phosphorylation in promoting fatty acid oxidation, mitochondrial biogenesis, and autophagy under conditions of high lipid availability.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2022)

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Article Cell & Tissue Engineering

Inflammatory exposure drives long-lived impairment of hematopoietic stem cell self-renewal activity and accelerated aging

Ruzhica Bogeska et al.

Summary: Infection or inflammation may lead to irreversible depletion of functional hematopoietic stem cells, resulting in long-term effects on tissue maintenance and regeneration.

CELL STEM CELL (2022)

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Article Multidisciplinary Sciences

Altered glycolysis triggers impaired mitochondrial metabolism and mTORC1 activation in diabetic β-cells

Elizabeth Haythorne et al.

Summary: Chronic hyperglycemia impairs insulin secretion and leads to diabetes. It has been found that a glucose metabolite is responsible for this effect, and reducing glucose metabolism during hyperglycemia can prevent the loss of beta-cell function.

NATURE COMMUNICATIONS (2022)

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Article Multidisciplinary Sciences

The dynamic clustering of insulin receptor underlies its signaling and is disrupted in insulin resistance

Alessandra Dall'Agnese et al.

Summary: This study found that insulin receptor (IR) forms dynamic clusters in human hepatocytes and adipocytes. Insulin stimulation promotes further incorporation of IR into these clusters, while in insulin-resistant cells, IR accumulation and dynamic behavior are reduced. Treatment with the commonly used drug metformin, which reduces reactive oxygen species, can rescue IR accumulation and dynamic behavior in insulin-resistant cells. These findings have implications for improved therapeutic approaches.

NATURE COMMUNICATIONS (2022)

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Article Medicine, Research & Experimental

Role of primary aging hallmarks in Alzheimer´s disease

Jin Zhao et al.

Theranostics (2022)

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Review Biochemistry & Molecular Biology

mTOR Complex 1 Content and Regulation Is Adapted to Animal Longevity

Natalia Mota-Martorell et al.

Summary: mTOR signaling pathway and mTORC1 play a crucial role in longevity and age-related diseases, with nutritional strategies being important in regulating mTORC1 activity.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Medicine, Research & Experimental

Inflammatory biomarkers, multi-morbidity, and biologic aging

Jennifer St Sauver et al.

Summary: This study investigated the association between multi-morbidity percentiles and interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-alpha. The results showed that individuals with higher multi-morbidity percentiles had significantly higher levels of IL-6 and TNF-alpha. However, IL-10 was not associated with multi-morbidity percentiles. The study suggests that multi-morbidity percentiles may be a useful clinical index of biological age for future studies, especially in women and individuals aged 70 and older.

JOURNAL OF INTERNATIONAL MEDICAL RESEARCH (2022)

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Article Respiratory System

Shortened Telomere Length in Sputum Cells of Bronchiectasis Patients is Associated with Dysfunctional Inflammatory Pathways

Hui Fang Lim et al.

Summary: This study found that telomere length in sputum of bronchiectasis patients is significantly shortened, and identified the signaling pathways and genes related to telomere shortening.

LUNG (2022)

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Review Biochemistry & Molecular Biology

Review Hallmarks of DNA replication stress

Sneha Saxena et al.

Summary: Faithful DNA replication is crucial for maintaining genomic integrity. However, the replication process is constantly challenged by DNA damage and other stresses, collectively known as replication stress. Cells have evolved complex cellular responses to cope with replication stress and maintain genomic stability.

MOLECULAR CELL (2022)

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Article Multidisciplinary Sciences

YAP/TAZ activity in stromal cells prevents ageing by controlling cGAS-STING

Hanna Lucie Sladitschek-Martens et al.

Summary: Ageing is closely related to the induction of cell senescence, with YAP/TAZ mechanotransduction playing a key role in the process. Declining YAP/TAZ activity during ageing leads to accelerated ageing and tissue degeneration, as it unleashes cGAS-STING signalling and promotes senescence. Sustaining YAP/TAZ mechanosignalling or inhibiting STING may be potential strategies to limit senescence-associated inflammation and improve healthy ageing.

NATURE (2022)

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Article Multidisciplinary Sciences

Sestrin mediates detection of and adaptation to low-leucine diets in Drosophila

Xin Gu et al.

Summary: Flies can sense and detect a diet deficient in essential amino acid leucine through the nutrient sensing of mTORC1 signaling.

NATURE (2022)

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Review Biochemistry & Molecular Biology

Cellular senescence and senolytics: the path to the clinic

Selim Chaib et al.

Summary: Cellular senescence has emerged as a promising therapeutic target for disorders across the lifespan; targeting persistent senescent cells causing tissue damage may delay, prevent, or alleviate multiple diseases.

NATURE MEDICINE (2022)

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Review Microbiology

Microbiota succession throughout life from the cradle to the grave

Cameron Martino et al.

Summary: This article summarizes the succession of human microbiota at different ages, focusing on the changes that occur from birth to death, including disruptions by disease or antibiotic use. The authors also discuss future research directions for studying the relationship between microbiota and age.

NATURE REVIEWS MICROBIOLOGY (2022)

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Review Urology & Nephrology

Role of the cGAS-STING pathway in systemic and organ-specific diseases

Sladjana Skopelja-Gardner et al.

Summary: Cells have sensors that recognize nucleic acids, triggering immune responses and promoting antiviral states. The cGAS-STING pathway, a recently identified DNA sensor pathway, binds DNA and produces a messenger molecule called cGAMP, leading to an inflammatory response. This pathway is involved in various diseases and has therapeutic potential.

NATURE REVIEWS NEPHROLOGY (2022)

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Article Medicine, General & Internal

PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer

Andrea Cercek et al.

Summary: This study found that mismatch repair-deficient, locally advanced rectal cancer is highly sensitive to PD-1 blockade. Additionally, no adverse events of grade 3 or higher have been reported, and no cases of progression or recurrence have been observed. Longer follow-up is needed to assess the duration of response.

NEW ENGLAND JOURNAL OF MEDICINE (2022)

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Article Geriatrics & Gerontology

Aging results in DNA damage and telomere dysfunction that is greater in endothelial versus vascular smooth muscle cells and is exacerbated in atheroprone regions

Samuel Bloom et al.

Summary: Aging leads to DNA damage and telomere dysfunction in both endothelial cells and vascular smooth muscle cells; however, the effects are more pronounced in endothelial cells and atheroprone arterial regions.

GEROSCIENCE (2022)

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Article Developmental Biology

Mechanosensing in macrophages and dendritic cells in steady-state and disease

Megan Lee et al.

Frontiers in Cell and Developmental Biology (2022)

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Review Biochemistry & Molecular Biology

Ageing and Low-Level Chronic Inflammation: The Role of the Biological Clock

Barbara Colombini et al.

Summary: Ageing is a multifactorial physiological manifestation that is closely related to inflammation and the functioning of the biological clock.

ANTIOXIDANTS (2022)

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Article Multidisciplinary Sciences

Zonated leucine sensing by Sestrin-mTORC1 in the liver controls the response to dietary leucine

Andrew L. Cangelosi et al.

Summary: This study reveals that Sestrin proteins play a crucial role in leucine sensing in mammals, showing their function in inhibiting mTORC1 activity, regulating white adipose tissue and muscle loss, and inducing FGF21 production in the liver. Moreover, it uncovers the zonated expression of Sestrin in the liver lobule, highlighting the spatial organization of nutrient sensing by the mTORC1 pathway.

SCIENCE (2022)

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Article Multidisciplinary Sciences

A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues

Dominik Saul et al.

Summary: The authors present and validate a senescence gene set called SenMayo, which can accurately identify senescent cells across different tissues and species. Using this gene set, senescent cells can be characterized at the single cell level and key intercellular signaling pathways can be identified.

NATURE COMMUNICATIONS (2022)

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Review Immunology

Endogenous Retroviruses (ERVs): Does RLR (RIG-I-Like Receptors)-MAVS Pathway Directly Control Senescence and Aging as a Consequence of ERV De-Repression?

Eros Di Giorgio et al.

Summary: Bi-directional transcription of hERVs is associated with autoimmune, neurodegenerative, and cancerous conditions. The regulation of hERVs is complex during aging, with peak activation in the sixties and decline in the nineties. The RLR-MAVS pathway plays a role in controlling hERV expression and maintaining stemness and tissue self-renewal.

FRONTIERS IN IMMUNOLOGY (2022)

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Review Immunology

Nrf2-mediated anti-inflammatory polarization of macrophages as therapeutic targets for osteoarthritis

Lin Wang et al.

Summary: Macrophages in synovial joints play an important role in the pathological process of osteoarthritis (OA). Their transition between pro-inflammatory and anti-inflammatory phenotypes can impact the intra-articular microenvironment. The inhibition of NF-kappa B signaling pathway is crucial in OA treatment, while the activation of Nrf2 signaling pathway, which has antioxidant and anti-inflammatory effects, and its crosstalk with NF-kappa B pathway have received less attention. Activating Nrf2 can inhibit M1 polarization and promote M2 polarization through multiple signaling pathways. Various potential candidates for activating Nrf2 to promote M2 phenotype macrophages in OA treatment are discussed.

FRONTIERS IN IMMUNOLOGY (2022)

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Article Endocrinology & Metabolism

Aging Relevant Metabolite Itaconate Inhibits Inflammatory Bone Loss

Yuting Wang et al.

Summary: Progressive bone loss during aging leads to osteoporosis, which is a common and impactful condition in elderly populations. This study found that a metabolite called itaconate plays a crucial regulatory role during inflammaging, inhibiting osteoclast activity and maintaining bone homeostasis.

FRONTIERS IN ENDOCRINOLOGY (2022)

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Article Biochemistry & Molecular Biology

Misfolded protein oligomers induce an increase of intracellular Ca2+ causing an escalation of reactive oxidative species

Giulia Fani et al.

Summary: Alzheimer's disease is characterized by the accumulation of amyloid beta (A beta) peptide in the brain, which leads to the formation of senile plaques. The aggregation process of A beta also generates smaller misfolded oligomers that contribute to disease progression. These oligomers interact with cell membranes, increasing intracellular Ca2+ levels and producing reactive oxygen species (ROS). Our study found that the increase in intracellular Ca2+ occurs faster than the increase in ROS levels after exposure to misfolded protein oligomers. Removing Ca2+ from the cell medium prevents the increase in intracellular Ca2+ and abolishes ROS production. Treating cells with antioxidant agents prevents ROS formation, but does not prevent the initial increase in Ca2+, allowing the cells to restore normal calcium levels. These findings suggest that Ca2+ influx triggers ROS production in cells challenged by aberrant protein oligomers.

CELLULAR AND MOLECULAR LIFE SCIENCES (2022)

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Article Cell Biology

An intercellular transfer of telomeres rescues T cells from senescence and promotes long-term immunological memory

Alessio Lanna et al.

Summary: It was discovered that some T cells can elongate telomeres by acquiring telomere vesicles from antigen-presenting cells, independently of telomerase action, which contributes to delaying the aging process.

NATURE CELL BIOLOGY (2022)

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Article Multidisciplinary Sciences

Sentinel p16 INK4a+ cells in the basement membrane form a reparative niche in the lung

Nabora S. Reyes et al.

SCIENCE (2022)

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Review Biology

The landscape of aging

Yusheng Cai et al.

Summary: This article discusses the aging process and age-associated diseases, emphasizing the importance of aging and healthy aging, and revealing the role of evolutionarily conserved genetic pathways and biological processes in controlling the rate of aging. It reviews the descriptive, conceptual, and interventive aspects of aging research at multiple levels.

SCIENCE CHINA-LIFE SCIENCES (2022)

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Review Geriatrics & Gerontology

The role of microglial autophagy in Parkinson's disease

Rui Zhu et al.

Summary: Parkinson's disease is the second most common neurodegenerative disease characterized by the abnormal accumulation of alpha-synuclein in the substantia nigra. This review outlines the pathways of microglial autophagy and explores its significance in the mechanism of PD and its potential as a therapeutic target.

FRONTIERS IN AGING NEUROSCIENCE (2022)

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Review Immunology

Activation induced cytidine deaminase: An old friend with new faces

Elif cakan et al.

Summary: AID is a protein in the APOBEC family that induces point mutations, regulates somatic hypermutation and class switch recombination. It plays important roles in B cell development and dysregulation of AID can lead to increased mutation load, translocations, and lymphomagenesis.

FRONTIERS IN IMMUNOLOGY (2022)

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Review Cell Biology

Sirtuin 1 in Host Defense during Infection

Jin Kyung Kim et al.

Summary: In this review, the roles of SIRT1 and its regulatory mechanisms during bacterial, viral, and parasitic infections are summarized. Potential antimicrobial treatments using SIRT1 modulators are also discussed. Understanding the function of SIRT1 in balancing immune homeostasis is of great importance for the development of new therapeutics for the treatment of infection and inflammatory disease.

CELLS (2022)

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Review Biochemistry & Molecular Biology

Aging and aging-related diseases: from molecular mechanisms to interventions and treatments

Jun Guo et al.

Summary: Aging is an irreversible pathophysiological process that results in declines in tissue and cell functions and increased risks of aging-related diseases. Current research focuses on understanding how various stresses contribute to aging and identifying interventions and treatments to promote healthy aging and longevity.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2022)

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Article Biochemistry & Molecular Biology

Mitochondrial PARP1 regulates NAD+-dependent poly ADP-ribosylation of mitochondrial nucleoids

Jong-Hyuk Lee et al.

Summary: This study demonstrates the presence of PARP1 and PARylation in mitochondria, and shows that NAD(+) can stimulate PARylation, with NAD(+)-dependent mtPARP1 activity contributing to mtDNA transcriptional regulation.

EXPERIMENTAL AND MOLECULAR MEDICINE (2022)

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Review Biochemistry & Molecular Biology

Epigenetic regulation of aging: implications for interventions of aging and diseases

Kang Wang et al.

Summary: Aging is accompanied by the decline of organismal functions and various genetic and epigenetic alterations. Understanding the epigenetic mechanisms in aging can lead to new strategies to delay aging, and interventions based on these mechanisms have shown promise in animal models.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2022)

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Review Medicine, Research & Experimental

Connecting aging biology and inflammation in the omics era

Keenan A. Walker et al.

Summary: Aging leads to the accumulation of damage and changes in cell structures, causing a proinflammatory state in blood and solid tissues. Inflammaging is associated with various age-related chronic diseases and loss of physical and cognitive function. Researchers have identified cellular senescence, mitochondrial dysfunction, impaired mitophagy, and DNA damage as potential factors contributing to inflammaging. Multiple omics approaches are being used to understand the complexity of inflammaging and find new therapeutic interventions. Additionally, there is emerging evidence linking inflammation to brain aging and neurodegenerative diseases.

JOURNAL OF CLINICAL INVESTIGATION (2022)

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Article Endocrinology & Metabolism

Systemic induction of senescence in young mice after single heterochronic blood exchange

Ok Hee Jeon et al.

Summary: Studies have shown that blood exchange between old and young mice induces cell and tissue senescence in young mice, but this induction can be attenuated by treating old mice with senolytic drugs before the exchange. Clearing senescent cells can rejuvenate old circulating blood and improve the health of multiple tissues.

NATURE METABOLISM (2022)

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Review Geriatrics & Gerontology

SIRT6 in Aging, Metabolism, Inflammation and Cardiovascular Diseases

Zhenyang Guo et al.

Summary: SIRT6, as an important NAD(+)-dependent enzyme, plays multiple roles in cellular signaling pathways and is closely associated with various physiological and pathological processes such as aging, metabolism, inflammation, and cardiovascular diseases. This article provides a detailed description of the specific substrates and molecular mechanisms of SIRT6, and reviews the recent advances in SIRT6 modulators as potential therapeutic agents for SIRT6-mediated diseases.

AGING AND DISEASE (2022)

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Review Immunology

Therapeutic mTOR blockade in systemic autoimmunity: Implications for antiviral immunity and extension of lifespan

Christian Geier et al.

Summary: The mTOR pathway plays a critical role in cell lineage specification, especially in adaptive immune responses. Its inhibition can reverse aberrant cell differentiation, potentially benefiting the treatment of autoimmune diseases and viral infections.

AUTOIMMUNITY REVIEWS (2021)

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Review Biochemistry & Molecular Biology

Telomeres: history, health, and hallmarks of aging

Deepavali Chakravarti et al.

Summary: The escalating social and economic burden of an aging world population has brought aging research into the spotlight. Through the lens of telomere biology, we can better understand the mechanisms of aging and the development of age-related diseases, providing insights for prevention and treatment.

CELL (2021)

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Article Endocrinology & Metabolism

A High-Fat Diet Attenuates AMPK α1 in Adipocytes to Induce Exosome Shedding and Nonalcoholic Fatty Liver Development In Vivo

Chenghui Yan et al.

Summary: The research suggests that inhibition of AMPK alpha 1 by a high-fat diet promotes NAFLD by increasing the number of AT CD36-containing exosomes. Activating AMPK with metformin can reduce exosome release from adipocytes and mitigate fatty liver development in WT and liver-specific Prka alpha 1(-/-) mice.

DIABETES (2021)

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Article Immunology

Activation of AMPK alpha 1 is essential for regulatory T cell function and autoimmune liver disease prevention

Huaiping Zhu et al.

Summary: AMPK plays a crucial role in maintaining the immunosuppressive function of Treg cells and confers protection against autoimmune liver disease.

CELLULAR & MOLECULAR IMMUNOLOGY (2021)

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Article Cardiac & Cardiovascular Systems

Deficient Chaperone-Mediated Autophagy Promotes Inflammation and Atherosclerosis

Qiao Lei et al.

Summary: The study reveals that impaired chaperone-mediated autophagy (CMA) during atherosclerosis progression increases NLRP3 inflammasome activation and IL-1β secretion, promoting vascular inflammation and atherosclerosis. This suggests a potential therapeutic strategy for atherosclerosis and other NLRP3 inflammasome/IL-1β-driven diseases through pharmacological activation of CMA.

CIRCULATION RESEARCH (2021)

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Review Biochemistry & Molecular Biology

Molecular Aspects of Senescence and Organismal Ageing-DNA Damage Response, Telomeres, Inflammation and Chromatin

Natalia Slawinska et al.

Summary: Cells can become senescent in response to stress, which can be beneficial in some cases like suppressing tumour development or promoting tissue repair, but may also contribute to the ageing process.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Review Biochemistry & Molecular Biology

Epigenetics of Aging and Aging-Associated Diseases

Dominik Saul et al.

Summary: Epigenetic changes occurring in various species during aging contribute directly to aging and age-related diseases. The impact on cellular processes is a key factor in the development of diseases such as cancer, diabetes, and neurodegenerative disorders.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Neurosciences

DNA Methyltransferase 1 Is Dysregulated in Parkinson's Disease via Mediation of miR-17

Hong-Qiu Zhang et al.

Summary: The study found that in Parkinson's disease, the downregulation of DNMT1 mediated by miR-17 leads to abnormal DNA methylation. Levels of miR-17 are elevated in PD models and plasma of patients, indicating a potential role in therapeutic regulation of DNA methylation.

MOLECULAR NEUROBIOLOGY (2021)

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Review Cell Biology

NAD+ metabolism and its roles in cellular processes during ageing

Anthony J. Covarrubias et al.

Summary: NAD(+) is a crucial coenzyme in redox reactions and plays a pivotal role in energy metabolism. Its levels decline with age, and raising NAD(+) levels is being explored as a potential strategy to extend human lifespan and healthspan. NAD(+) influences key cellular processes and functions, including metabolic pathways, DNA repair, and cellular senescence, with implications for healthy aging and age-related diseases.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2021)

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Article Cell Biology

Mechanical Stiffness Controls Dendritic Cell Metabolism and Function

Mainak Chakraborty et al.

Summary: This study reveals that static tension impacts immune cell function, maturation, and metabolism, with cells grown at physiological resting stiffness showing reduced proliferation, activation, and cytokine production compared to cells grown under higher stiffness. The findings suggest that mechanical stiffness is a critical environmental cue affecting dendritic cells and innate immunity.

CELL REPORTS (2021)

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Review Geriatrics & Gerontology

Gut microbiota as the key controllers of healthy aging of elderly people

Emeline Ragonnaud et al.

Summary: External factors like lifestyle and diet play a crucial role in human healthy aging and longevity, targeting the gut microbiome. Dysbiosis, a major shift in gut microbiota composition, can trigger harmful inflammation events leading to premature death in elderly individuals.

IMMUNITY & AGEING (2021)

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Review Immunology

Mitophagy in neurological disorders

Lijun Zhang et al.

Summary: Selective autophagy, particularly mitophagy, plays a crucial role in maintaining cellular homeostasis by removing excess protein aggregates and damaged mitochondria. Dysfunctional mitophagy can lead to neurodegeneration, while efficient mitophagy responses can prevent the accumulation of damaged mitochondria and provide neuroprotective effects. Targeting mitophagy may hold potential for the treatment of neurodegenerative diseases and acute brain injuries, despite the complex and sometimes dual nature of its mechanisms.

JOURNAL OF NEUROINFLAMMATION (2021)

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Review Geriatrics & Gerontology

Emerging roles of oxidative stress in brain aging and Alzheimer's disease

Andra Ionescu-Tucker et al.

Summary: Reactive oxygen species (ROS) are metabolic byproducts that can be toxic at high levels and have been linked to cognitive aging and neurodegenerative diseases. Therapeutics like antioxidants, caloric restriction, and physical activity can reduce oxidation and prevent cognitive decline in brain aging and AD. Long term physical activity shows promise in improving cognitive health by reducing ROS levels and promoting optimal function.

NEUROBIOLOGY OF AGING (2021)

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Article Multidisciplinary Sciences

Nuclear sensing of breaks in mitochondrial DNA enhances immune surveillance

Marco Tigano et al.

Summary: The study reveals that mtDSBs activate a type-I interferon response, leading to the phosphorylation of STAT1 and activation of interferon-stimulated genes. After breaks in mtDNA, herniation mediated by BAX and BAK releases mitochondrial RNA into the cytoplasm and triggers a RIG-I-MAVS-dependent immune response.

NATURE (2021)

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Review Physiology

REGULATION AND METABOLIC FUNCTIONS OF mTORC1 AND mTORC2

Angelia Szwed et al.

Summary: Cells metabolize nutrients for growth and proliferation, with mTOR playing a key role in integrating growth and metabolism through the protein complexes mTORC1 and mTORC2. Study of mTORC1 and mTORC2 has expanded our understanding of cellular metabolism regulation and functions.

PHYSIOLOGICAL REVIEWS (2021)

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Article Multidisciplinary Sciences

p21 produces a bioactive secretome that places stressed cells under immunosurveillance

Ines Sturmlechner et al.

Summary: The cell-cycle inhibitor p21 activates Rb-dependent transcription to generate a complex bioactive secretome, known as PASP, which includes chemokine CXCL14 that attracts macrophages. Macrophages disengage if cells normalize p21 within 4 days, but persisting p21 induction leads to M1 polarization and cytotoxic T cell response for eliminating target cells, including preneoplastic cells. Thus, p21 concurrently induces proliferative arrest and immunosurveillance of cells under duress.

SCIENCE (2021)

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Article Substance Abuse

Effects of electronic cigarette e-liquid flavouring on cigarette craving

Maddy L. Dyer et al.

Summary: The study found no evidence to suggest that nicotine-containing fruit/sweet-flavoured and unflavoured e-liquids have different effects on cigarette cravings after 1 week of use. Further research is needed to explore if differences emerge over longer periods of exposure and extend to smoking cessation outcomes.

TOBACCO CONTROL (2021)

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Article Geriatrics & Gerontology

Hyper-metabolic B cells in the spleens of old mice make antibodies with autoimmune specificities

Daniela Frasca et al.

Summary: Aging is associated with increased intrinsic B cell inflammation, decreased protective antibody responses, and increased autoimmune antibody responses. The subset of ABCs in the spleen of old mice, whose frequencies and numbers increase with age, is mainly responsible for the expression of inflammatory markers and secretion of autoimmune antibodies. These hyper-inflammatory and hyper-metabolic ABCs might lead to the generation of pathogenic B cells with autoimmune specificities.

IMMUNITY & AGEING (2021)

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Article Biochemistry & Molecular Biology

Neutrophils induce paracrine telomere dysfunction and senescence in ROS-dependent manner

Anthony Lagnado et al.

Summary: The research shows that neutrophils cause oxidative damage to telomeres in non-immune cells, promoting cellular senescence. In aged liver, senescent cells recruit neutrophils, potentially leading to the spread of senescence.

EMBO JOURNAL (2021)

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Review Endocrinology & Metabolism

Ovarian Aging: Role of Pituitary-Ovarian Axis Hormones and ncRNAs in Regulating Ovarian Mitochondrial Activity

Marco Colella et al.

Summary: The number and function of mitochondria in oocytes decrease with age progression, potentially playing a key role in ovarian aging. Imbalance in circulating hormones and peptides along the neuroendocrine axis can serve as a biochemical sign of ovarian aging, while mitochondrial ncRNAs may be potential diagnostic markers and therapeutic targets.

FRONTIERS IN ENDOCRINOLOGY (2021)

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Review Biochemistry & Molecular Biology

Reprogramming: Emerging Strategies to Rejuvenate Aging Cells and Tissues

Quentin Alle et al.

Summary: Aging is traditionally seen as an unavoidable process, but new strategies have been developed to delay or reverse aging. Some of these approaches may have medical applications to improve healthspan and longevity.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Review Cell Biology

The Role of Immune Cells in Oxi-Inflamm-Aging

Irene Martinez de Toda et al.

Summary: Aging is a result of deteriorating homeostatic systems, where chronic oxidative stress and inflammation play crucial roles. The weakening immune system can be used as an indicator of an individual's rate of aging. Lifestyle conditions like social environment, nutrition, and exercise can impact longevity by affecting immune cell function and contributing to oxidative and inflammatory stress.

CELLS (2021)

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Review Oncology

Pyroptosis: a new paradigm of cell death for fighting against cancer

Yixin Tan et al.

Summary: Pyroptosis is an inflammatory form of cell death with tumor suppressive function and the ability to evoke anti-tumor immune responses. Cancer therapies induce pyroptosis, enhancing anti-tumor immunity, but also leading to side effects on normal cells.

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH (2021)

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Review Cell Biology

Interactions Among lncRNA/circRNA, miRNA, and mRNA in Musculoskeletal Degenerative Diseases

Yi-Li Zheng et al.

Summary: Musculoskeletal degenerative diseases (MSDDs) encompass a range of pathological conditions affecting muscle, bone, cartilage, joints, and connective tissues. Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) play key roles in biological regulation and are potential targets for therapeutic interventions in MSDD. Further research is needed to uncover the mutual regulatory mechanisms between lncRNA/circRNA regulation and effective therapeutic interventions in MSDD pathology.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2021)

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Review Medicine, General & Internal

Crosstalk Between ER Stress, Autophagy and Inflammation

Sandhya Chipurupalli et al.

Summary: The endoplasmic reticulum (ER) is crucial for protein synthesis, folding, sensing cellular stress and maintaining cellular homeostasis. The unfolded protein response (UPR) expands protein folding capacity, reduces protein synthesis, enhances ER-associated protein degradation (ERAD), and amplifies cytokine-mediated inflammatory responses. UPR also activates autophagy, which limits inflammation and provides cyto-protection by attenuating ER-stress.

FRONTIERS IN MEDICINE (2021)

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Article Neurosciences

The mTOR/NF-κB Pathway Mediates Neuroinflammation and Synaptic Plasticity in Diabetic Encephalopathy

Ting Xu et al.

Summary: Diabetic encephalopathy, characterized by neuroinflammation and aberrant synaptogenesis, involves the mTOR and NF-kappa B signaling pathways. Inhibiting mTOR and NF-kappa B can reduce inflammatory cytokines expression and increase synaptic proteins, leading to the improvement of cognitive decline in diabetic models. This study suggests that targeting the mTOR/NF-kappa B pathway could be a potential therapeutic strategy for treating diabetic encephalopathy and related cognitive impairments.

MOLECULAR NEUROBIOLOGY (2021)

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Review Immunology

Hallmarks of T cell aging

Maria Mittelbrunn et al.

Summary: In this Review, Mittelbrunn and Kroemer propose ten molecular hallmarks as common denominators of T cell aging, which include primary and secondary hallmarks explaining the manifestation of T cell aging and its impact on overall deterioration. The challenge now is to weigh the relative impact of these hallmarks on T cell aging and understand their interconnections, with the goal of defining molecular targets for interventions in the aging process.

NATURE IMMUNOLOGY (2021)

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Editorial Material Immunology

The impact of age-related hypomethylated DNA on immune signaling upon cellular demise

Lauren A. Urban et al.

Summary: Aging is associated with decreased antigen-specific immunity and increased chronic inflammation, with DNA hypomethylation potentially playing a role in age-related inflammation.

TRENDS IN IMMUNOLOGY (2021)

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Article Multidisciplinary Sciences

SARS-CoV-2 infection rewires host cell metabolism and is potentially susceptible to mTORC1 inhibition

Peter J. Mullen et al.

Summary: This study revealed that SARS-CoV-2 infection alters host cell metabolism by increasing glucose entry into the TCA cycle and reducing oxidative glutamine metabolism. Additionally, infection with SARS-CoV-2 activates mTORC1, and inhibiting mTORC1 can suppress viral replication in kidney epithelial cells and lung ALI cultures. These findings suggest that targeting mTORC1 could be a potential treatment strategy for COVID-19 patients.

NATURE COMMUNICATIONS (2021)

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Article Cell Biology

Persistent NF-κB activation in muscle stem cells induces proliferation-independent telomere shortening

Elisia D. Tichy et al.

Summary: Repeated cycles of damage and repair in muscle disorders like DMD can lead to inefficiency in muscle stem cell response. The early telomere shortening in diseased MuSCs is associated with aberrant NF-kappa B activation, leading to severe skeletal muscle defects. NF-kappa B plays a role in regulating stem-cell-specific telomere length and could be a common mechanism in diseases characterized by chronic inflammation.

CELL REPORTS (2021)

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Article Endocrinology & Metabolism

Aging Reduces Insulin Clearance in Mice

Carine Marmentini et al.

Summary: Although insulin sensitivity was unaffected in old mice, glucose tolerance appeared to increase during the intraperitoneal glucose tolerance test, accompanied by higher plasma insulin levels. The reduced insulin clearance in old mice may be related to the decreased hepatic CEACAM1 and IDE function.

FRONTIERS IN ENDOCRINOLOGY (2021)

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Review Cell Biology

The Power of Stress: The Telo-Hormesis Hypothesis

Maria Sol Jacome Burbano et al.

Summary: Adaptive response to stress is a survival strategy conserved across evolution. Scientists have explored the potential benefits of changing telomeres in response to stress, suggesting stress-induced telomere signaling with hormetic effects.

CELLS (2021)

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Review Cell Biology

Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype

Ruchi Kumari et al.

Summary: Cellular senescence is a stable cell cycle arrest triggered in response to various stimuli, characterized by dynamic changes in senescent cells. It has both positive effects on tissue repair and anti-cancer mechanisms, but can also negatively impact organismal health. Multiple pathways, including p53/p21 and p16/pRB, play central roles in regulating this process.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2021)

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Article Cell Biology

miR-21 and miR-146a: The microRNAs of inflammaging and age-related diseases

Fabiola Olivieri et al.

Summary: Inflammaging is a key concept in understanding how aging contributes to the development of age-related diseases, with a focus on the role of miRNAs in regulating inflammatory pathways. The assessment of individual genetic make-up alone is insufficient to depict the trajectories of age-related inflammation, and studies have shown that circulating inflammamiRs could be used to measure the degree of inflammaging.

AGEING RESEARCH REVIEWS (2021)

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Article Cell Biology

Interactions among mTORC, AMPK and SIRT: a computational model for cell energy balance and metabolism

Mehrshad Sadria et al.

Summary: Cells adapt their metabolism and activities in response to signals from their surroundings, and proteins like mTOR, AMPK, and sirtuins play essential roles in regulating metabolic stress and energy balance. The computational model developed in this study sheds light on complex interactions among signaling pathways, offering insights for novel treatment approaches in diseases such as cancer.

CELL COMMUNICATION AND SIGNALING (2021)

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Article Oncology

Reducing lipofuscin accumulation and cardiomyocytic senescence of aging heart by enhancing autophagy

Wen-wen Li et al.

Summary: The study found that in aging hearts, there is an increase in lipofuscin accumulation and senescent cardiomyocytes, along with a decrease in autophagy levels. Enhancing autophagy with rapamycin was effective in reducing lipofuscinogenesis and promoting degradation of lipofuscin, offering a novel therapy for alleviating lipofuscin accumulation and myocardial senescence.

EXPERIMENTAL CELL RESEARCH (2021)

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Article Biochemistry & Molecular Biology

The innate immune kinase TBK1 directly increases mTORC2 activity and downstream signaling to Akt

Aaron Seth Tooley et al.

Summary: TBK1 can directly activate mTOR complex 2 (mTORC2) to promote Akt phosphorylation, involving in cellular metabolism and proliferation. Interaction between TBK1 and mTOR serves as key nodes in two major signaling networks.

JOURNAL OF BIOLOGICAL CHEMISTRY (2021)

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Review Cell Biology

Oxidative stress in oocyte aging and female reproduction

Ling Wang et al.

Summary: Oxidative stress plays a significant role in oocyte aging, leading to a gradual decrease in oocyte quantity and quality, as well as various reproductive pathologies. Strategies to delay oocyte aging include targeting oxidative stress through autophagy antioxidant pathways and antioxidants, along with creating a hypoxic culture environment for oocytes in vitro.

JOURNAL OF CELLULAR PHYSIOLOGY (2021)

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Article Immunology

mTORC1 Signaling Regulates Proinflammatory Macrophage Function and Metabolism

Samuel L. Collins et al.

Summary: Metabolic programming is closely linked to immune cell function, with mTOR signaling as a key regulator. While mTORC2 signaling is crucial for M2 macrophage generation, the role of mTORC1 signaling remains controversial. Inhibiting mTORC1 signaling enhances M1 macrophage function, despite defects in glycolytic metabolism, by inhibiting sirtuins and enhancing histone acetylation.

JOURNAL OF IMMUNOLOGY (2021)

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Review Multidisciplinary Sciences

The role of retrotransposable elements in ageing and age-associated diseases

Vera Gorbunova et al.

Summary: The article discusses the impact of transposons on aging and age-related diseases in complex metazoan organisms, focusing on the activity of retrotransposons in particular. Research has shown that the activity of retrotransposons in somatic tissues during an individual's lifespan influences health and well-being, intersecting with our own physiology.

NATURE (2021)

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Article Multidisciplinary Sciences

Aged skeletal stem cells generate an inflammatory degenerative niche

Thomas H. Ambrosi et al.

Summary: Aging of skeletal stem cells in mice alters bone marrow signaling and differentiation of bone and blood lineages, resulting in fragile bones with poor regeneration. Aged SSCs have decreased bone-forming potential but produce more stromal lineages expressing pro-inflammatory cytokines, contributing to bone marrow niche transformation.

NATURE (2021)

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Article Cell Biology

Puma, noxa, p53, and p63 differentially mediate stress pathway induced apoptosis

Jun Wang et al.

Summary: Cellular stress can lead to human disease pathologies due to aberrant cell death. The study found both common and unique molecular pathways involved in different stress responses, with p53 and puma playing key roles. The data suggests that Puma may be the key mediator of p53-dependent apoptosis, and inhibitors targeting Puma could have therapeutic applications.

CELL DEATH & DISEASE (2021)

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Review Genetics & Heredity

Losing DNA methylation at repetitive elements and breaking bad

Xena Giada Pappalardo et al.

Summary: Hypomethylation of repetitive sequences is common in various human diseases, indicating that the methylation status of these elements may play a role in maintaining human health. This suggests potential therapeutic strategies focused on modulating DNA methylation of repetitive sequences.

EPIGENETICS & CHROMATIN (2021)

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Review Oncology

Cellular reprogramming and epigenetic rejuvenation

Daniel J. Simpson et al.

Summary: Ageing is inevitable, but recent research has shown that slowing down and reversing the ageing process may be possible through induced pluripotent stem cells and epigenetic rejuvenation. Reprogramming-induced rejuvenation strategies offer promising candidates for safely reducing biological age.

CLINICAL EPIGENETICS (2021)

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Article Cell & Tissue Engineering

Sestrins regulate muscle stem cell metabolic homeostasis

Benjamin A. Yang et al.

Summary: The maintenance of metabolic pathways in MuSCs is crucial for the preservation of quiescence, with Sestrins playing a key role in this function. Loss of Sestrins during aging can lead to loss of MuSCs and reduced muscle regeneration capacity.

STEM CELL REPORTS (2021)

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Article Immunology

Evolution of Human Memory B Cells From Childhood to Old Age

Michela Ciocca et al.

Summary: The decline of the immune system in aging leads to decreased susceptibility to infections and reduced response to vaccination, especially in reacting to new pathogens. Research shows that elderly individuals have a significant reduction in CD27(dull) memory B cells, while having a higher population of specialized antigen-selected CD27(bright) memory B cells. Additionally, B cells from older individuals produce significantly fewer IgM and IgA antibodies compared to younger individuals after in vitro stimulation.

FRONTIERS IN IMMUNOLOGY (2021)

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Review Cell Biology

T Cell Immunosenescence in Aging, Obesity, and Cardiovascular Disease

Kohsuke Shirakawa et al.

Summary: Despite advancements in preventive medicine, cardiovascular disease (CVD) remains the leading cause of death worldwide. Inflammation, particularly related to T cell immunosenescence, is seen as a key target for CVD prevention.

CELLS (2021)

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Review Cell Biology

Inflammation and Aging of Hematopoietic Stem Cells in Their Niche

Daozheng Yang et al.

Summary: Hematopoietic stem cells (HSCs) play a crucial role in lifelong blood cell production. Aging impacts HSC function, with inflammation emerging as a key factor in driving this process. Both intrinsic and extrinsic factors contribute to HSC aging.

CELLS (2021)

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Review Cell Biology

Immunoproteasome Function in Normal and Malignant Hematopoiesis

Nuria Tubio-Santamaria et al.

Summary: The ubiquitin-proteasome system (UPS) plays a crucial role in maintaining protein homeostasis, with inhibitors of the immunoproteasome showing potential as a targeted therapy for hematologic malignancies.

CELLS (2021)

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Review Biochemistry & Molecular Biology

Proteostasis Dysfunction in Aged Mammalian Cells. The Stressful Role of Inflammation

Diego Ruano

Summary: Aging is a progressive and irreversible biological process that leads to an increase in morbidity due to physiological deterioration. As the global population ages, the incidence of age-related pathologies such as cancer, diabetes, and neurodegenerative disorders is expected to rise. Cellular proteostasis disruption is a key feature of normal aging and is believed to play a role in the development of age-related diseases.

FRONTIERS IN MOLECULAR BIOSCIENCES (2021)

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Review Biochemistry & Molecular Biology

Roles and mechanisms of exosomal non-coding RNAs in human health and diseases

Chen Li et al.

Summary: Exosomes act as mediators of cell-to-cell communication, playing a crucial role in regulating human health and diseases through non-coding RNA. Changes in exosomal ncRNAs may lead to tissue dysfunction, aging, and diseases.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2021)

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Article Biochemistry & Molecular Biology

Mesenchymal stem cell-derived small extracellular vesicles mitigate oxidative stress-induced senescence in endothelial cells via regulation of miR-146a/Src

Xian Xiao et al.

Summary: Research has shown that small extracellular vesicles play a crucial role in mitigating endothelial cell senescence and stimulating angiogenesis through the miR-146a/Src mechanism.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2021)

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Review Cell Biology

SARS-CoV-2, COVID-19 and the aging immune system

Juliet M. Bartleson et al.

Summary: The COVID-19 pandemic poses a greater risk for severe disease and death in older adults and individuals with age-related metabolic and cardiovascular diseases. Interventions targeting immunosenescence may be crucial in reducing mortality and disability caused by the pandemic, ultimately improving complications associated with severe COVID-19 in individuals of all ages.

NATURE AGING (2021)

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Review Biochemistry & Molecular Biology

Pattern recognition receptors in health and diseases

Danyang Li et al.

Summary: Pattern recognition receptors (PRRs) are a class of receptors that can directly recognize specific molecular structures on pathogens, apoptotic host cells, and damaged senescent cells, bridging nonspecific immunity and specific immunity. Through the recognition and binding of ligands, PRRs can produce immunoprotective effects against infections and tumors. Research on PRRs and their ligands has greatly enhanced understanding of the signaling pathways involved, providing insights for the treatment of immune-related diseases and tumors.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2021)

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Article Genetics & Heredity

The impact of age on genetic risk for common diseases

Xilin Jiang et al.

Summary: The study found that genetic factors exhibit age-varying relative risk profiles for several diseases, with most variants having a stronger impact on risk among younger populations. These patterns cannot be explained by a simple model and likely involve multiple factors such as environmental influences.

PLOS GENETICS (2021)

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Review Cell Biology

Autophagy in healthy aging and disease

Yahyah Aman et al.

Summary: This Review discusses the recent research on the mechanisms and roles of autophagy in health, aging, and disease, and how drugs modulating autophagy process could be used to suppress age-associated diseases. It examines emerging features of autophagy and proposes the potential links to aging and disease progression. The review also highlights the importance of understanding the interplay between autophagy and age-related pathologies for the development of clinical applications promoting long-term health.

NATURE AGING (2021)

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Review Geriatrics & Gerontology

Induction of T Cell Senescence by Cytokine Induced Bystander Activation

Attiya A. Abbas et al.

Summary: As people age, the immune system undergoes changes that may lead to increased vulnerability to infectious diseases, particularly in elderly individuals. Senescent T cells with a NK-like phenotype play a significant role in this susceptibility. Understanding the characteristics of these NK-like senescent T cells has important implications in health and disease management.

FRONTIERS IN AGING (2021)

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Article Cell Biology

An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging

Nazish Sayed et al.

Summary: From analyzing the blood immunome of 1,001 individuals aged 8-96 years, researchers have developed an inflammatory clock of aging (iAge) that tracks with multimorbidity, immunosenescence, frailty, and cardiovascular aging, and is associated with exceptional longevity in centenarians. The chemokine CXCL9 plays a key role in age-related chronic inflammation and is a major contributor to iAge.

NATURE AGING (2021)

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Review Biochemistry & Molecular Biology

Inflammation, epigenetics, and metabolism converge to cell senescence and ageing: the regulation and intervention

Xudong Zhu et al.

Summary: Significant progress has been made in ageing research, with a focus on epigenetic dynamics and immunometabolic reprogramming in relation to cell senescence. These hotspots not only shape cell identity, but also play a role in cell fate determination. Potential therapeutic interventions targeting cell senescence and regulatory mechanisms using state-of-the-art techniques are discussed.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2021)

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Review Immunology

The cGAS-STING pathway as a therapeutic target in inflammatory diseases

Alexiane Decout et al.

Summary: The cGAS-STING signaling pathway plays a crucial role in inflammation in infection, cellular stress, and tissue damage settings. It has the ability to sense and regulate cellular responses to DNA and has the potential to be targeted in the treatment of various inflammatory diseases.

NATURE REVIEWS IMMUNOLOGY (2021)

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Article Urology & Nephrology

Aging increases oxidative stress in semen

Mitsuru Nago et al.

Summary: As age increases, sperm motility decreases and semen oxidative stress increases, with a significant increase in sORP positivity after the age of 34.

INVESTIGATIVE AND CLINICAL UROLOGY (2021)

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Article Biochemistry & Molecular Biology

Cell-centric hypotheses of aging

Siamak Tabibzadeh

Summary: Aging in mammals leads to various age-related pathologies, with cell damage being considered as the main cause, involving multiple cell-centric hypotheses and theories.

FRONTIERS IN BIOSCIENCE-LANDMARK (2021)

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Review Genetics & Heredity

MicroRNAs as modulators of longevity and the aging process

Holly E. Kinser et al.

HUMAN GENETICS (2020)

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Article Allergy

PSMB10, the last immunoproteasome gene missing for PRAAS

Guillaume Sarrabay et al.

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY (2020)

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Review Biochemistry & Molecular Biology

Autophagosome-Lysosome Fusion

Peter Lorincz et al.

JOURNAL OF MOLECULAR BIOLOGY (2020)

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Review Hematology

Understanding intrinsic hematopoietic stem cell aging

Eva Mejia-Ramirez et al.

HAEMATOLOGICA (2020)

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Review Cell Biology

mTOR at the nexus of nutrition, growth, ageing and disease

Grace Y. Liu et al.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2020)

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Review Multidisciplinary Sciences

The biology, function, and biomedical applications of exosomes

Raghu Kalluri et al.

SCIENCE (2020)

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Article Cell Biology

Pharmacological enhancement of TFEB-mediated autophagy alleviated neuronal death in oxidative stress-induced Parkinson's disease models

Xu-Xu Zhuang et al.

CELL DEATH & DISEASE (2020)

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Review Multidisciplinary Sciences

Mitochondrial TCA cycle metabolites control physiology and disease

Inmaculada Martinez-Reyes et al.

NATURE COMMUNICATIONS (2020)

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Review Endocrinology & Metabolism

Mechanism of increased risk of insulin resistance in aging skeletal muscle

Jian Shou et al.

DIABETOLOGY & METABOLIC SYNDROME (2020)

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Article Cell Biology

Epigenome signatures landscaped by histone H3K9me3 are associated with the synaptic dysfunction in Alzheimer's disease

Min Young Lee et al.

AGING CELL (2020)

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Article Cell Biology

ATM is a key driver of NF-κB-dependent DNA-damage-induced senescence, stem cell dysfunction and aging

Jing Zhao et al.

AGING-US (2020)

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Article Hematology

Aging-induced IL27Ra signaling impairs hematopoietic stem cells

Hanqing He et al.

BLOOD (2020)

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Review Geriatrics & Gerontology

Succination of Protein Thiols in Human Brain Aging

Mariona Jove et al.

FRONTIERS IN AGING NEUROSCIENCE (2020)

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Article Biochemistry & Molecular Biology

Ketogenic Diets Alter the Gut Microbiome Resulting in Decreased Intestinal Th17 Cells

Qi Yan Ang et al.

CELL (2020)

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Article Cell Biology

Metformin Enhances Autophagy and Normalizes Mitochondrial Function to Alleviate Aging-Associated Inflammation

Leena P. Bharath et al.

CELL METABOLISM (2020)

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Article Biochemistry & Molecular Biology

A proteomic atlas of senescence-associated secretomes for aging biomarker development

Nathan Basisty et al.

PLOS BIOLOGY (2020)

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Article Cell & Tissue Engineering

Restoring aged stem cell functionality: Current progress and future directions

Kevin Spehar et al.

STEM CELLS (2020)

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Review Genetics & Heredity

ER stress activates immunosuppressive network: implications for aging and Alzheimer's disease

Antero Salminen et al.

JOURNAL OF MOLECULAR MEDICINE-JMM (2020)

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Editorial Material Biochemistry & Molecular Biology

Unfolded Protein Response (UPR) Controls Major Senescence Hallmarks

Corinne Abbadie et al.

TRENDS IN BIOCHEMICAL SCIENCES (2020)

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Article Multidisciplinary Sciences

Transient non-integrative expression of nuclear reprogramming factors promotes multifaceted amelioration of aging in human cells

Tapash Jay Sarkar et al.

NATURE COMMUNICATIONS (2020)

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Article Biology

Adjusting for age improves identification of gut microbiome alterations in multiple diseases

Tarini S. Ghosh et al.

ELIFE (2020)

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Review Endocrinology & Metabolism

The Immune Landscape of Visceral Adipose Tissue During Obesity and Aging

Saad Khan et al.

FRONTIERS IN ENDOCRINOLOGY (2020)

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Article Multidisciplinary Sciences

FOXO1 deficiency impairs proteostasis in aged T cells

Jun Jin et al.

SCIENCE ADVANCES (2020)

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Review Cell Biology

Role of c-Jun N-terminal Kinase (JNK) in Obesity and Type 2 Diabetes

Justin Hou Ming Yung et al.

CELLS (2020)

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Article Multidisciplinary Sciences

Bacterial metabolism of bile acids promotes generation of peripheral regulatory T cells

Clarissa Campbell et al.

NATURE (2020)

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Review Cell Biology

MitophAging: Mitophagy in Aging and Disease

Daniela Bakula et al.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2020)

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Article Clinical Neurology

IL-1β/IL-1R1 signaling induced by intranasal lipopolysaccharide infusion regulates alpha-synuclein pathology in the olfactory bulb, substantia nigra and striatum

Haichen Niu et al.

BRAIN PATHOLOGY (2020)

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Article Oncology

Telomere Stress Potentiates STING-Dependent Anti-tumor Immunity

Ilgen Mender et al.

CANCER CELL (2020)

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Article Cell Biology

Small Extracellular Vesicles Have GST Activity and Ameliorate Senescence-Related Tissue Damage

Juan Antonio Fafian-Labora et al.

CELL METABOLISM (2020)

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Review Cell Biology

Liquid-liquid phase separation in autophagy

Nobuo N. Noda et al.

JOURNAL OF CELL BIOLOGY (2020)

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Article Geriatrics & Gerontology

Poor mitochondrial health and systemic inflammation? Test of a classic hypothesis in the Baltimore Longitudinal Study of Aging

Marta Zampino et al.

GEROSCIENCE (2020)

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Article Medicine, Research & Experimental

The senescence-associated secretome as an indicator of age and medical risk

Marissa J. Schafer et al.

JCI INSIGHT (2020)

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Article Immunology

T reg-specific insulin receptor deletion prevents diet-induced and age-associated metabolic syndrome

Dan Wu et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2020)

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Article Multidisciplinary Sciences

Human Gut Microbiome Aging Clock Based on Taxonomic Profiling and Deep Learning

Fedor Galkin et al.

ISCIENCE (2020)

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Review Cell Biology

Single-cell analyses of aging, inflammation and senescence

Bora Uyar et al.

AGEING RESEARCH REVIEWS (2020)

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Article Cell Biology

Autophagy-Sirt3 axis decelerates hematopoietic aging

Yixuan Fang et al.

AGING CELL (2020)

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Article Neurosciences

Ammonia-Induced Glial-Inflammaging

Larissa Daniele Bobermin et al.

MOLECULAR NEUROBIOLOGY (2020)

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Review Immunology

Mitochondria, immunosenescence and inflammaging: a role for mitokines?

Maria Conte et al.

SEMINARS IN IMMUNOPATHOLOGY (2020)

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Review Virology

Silencing and Transcriptional Regulation of Endogenous Retroviruses: An Overview

Franziska K. Geis et al.

VIRUSES-BASEL (2020)

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Review Cell Biology

The Role of Exosomal microRNAs and Oxidative Stress in Neurodegenerative Diseases

Xiaoyu Wang et al.

OXIDATIVE MEDICINE AND CELLULAR LONGEVITY (2020)

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Article Mathematical & Computational Biology

ROS networks: designs, aging, Parkinson's disease and precision therapies

Alexey N. Kolodkin et al.

NPJ SYSTEMS BIOLOGY AND APPLICATIONS (2020)

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Review Nutrition & Dietetics

The Gut Microbiome, Aging, and Longevity: A Systematic Review

Varsha D. Badal et al.

NUTRIENTS (2020)

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Review Cell Biology

Amyotrophic Lateral Sclerosis and Autophagy: Dysfunction and Therapeutic Targeting

Azin Amin et al.

CELLS (2020)

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Review Neurosciences

Neuroimmunomodulation by estrogen in health and disease

Hannah P. Priyanka et al.

AIMS NEUROSCIENCE (2020)

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Article Endocrinology & Metabolism

Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages

Anthony J. Covarrubias et al.

NATURE METABOLISM (2020)

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Article Medicine, Research & Experimental

Human endogenous retrovirus HERV-K(HML-2) RNA causes neurodegeneration through Toll-like receptors

Paul Dembny et al.

JCI INSIGHT (2020)

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Article Physiology

Oxidative Stress in Pulmonary Fibrosis

Eva Otoupalova et al.

COMPREHENSIVE PHYSIOLOGY (2020)

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Review Neurosciences

A role for autophagy in Huntington's disease

Katherine R. Croce et al.

NEUROBIOLOGY OF DISEASE (2019)

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Article Cell Biology

LINE1 Derepression in Aged Wild-Type and SIRT6-Deficient Mice Drives Inflammation

Matthew Simon et al.

CELL METABOLISM (2019)

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Article Cell Biology

Telomere Dysfunction Induces Sirtuin Repression that Drives Telomere-Dependent Disease

Hisayuki Amano et al.

CELL METABOLISM (2019)

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Article Immunology

Insulin Resistance in Macrophages Alters Their Metabolism and Promotes an M2-Like Phenotype

Eleftheria Ieronymaki et al.

JOURNAL OF IMMUNOLOGY (2019)

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Review Medicine, Research & Experimental

Transmission of α-synuclein seeds in neurodegenerative disease: recent developments

Richard J. Karpowicz et al.

LABORATORY INVESTIGATION (2019)

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Article Biochemistry & Molecular Biology

Histone Acetyltransferase p300 Induces De Novo Super-Enhancers to Drive Cellular Senescence

Payel Sen et al.

MOLECULAR CELL (2019)

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Article Multidisciplinary Sciences

Autophagic cell death restricts chromosomal instability during replicative crisis

Joe Nassour et al.

NATURE (2019)

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Article Multidisciplinary Sciences

L1 drives IFN in senescent cells and promotes age-associated inflammation

Marco De Cecco et al.

NATURE (2019)

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Article Multidisciplinary Sciences

Age-related inflammation triggers skeletal stem/progenitor cell dysfunction

Anne Marie Josephson et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2019)

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Article Biochemistry & Molecular Biology

Surface-Binding to Cardiolipin Nanodomains Triggers Cytochrome c Pro-apoptotic Peroxidase Activity via Localized Dynamics

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STRUCTURE (2019)

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Insulin Receptor Associates with Promoters Genome-wide and Regulates Gene Expression

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CELL (2019)

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Aryl hydrocarbon receptor agonist indigo protects against obesity-related insulin resistance through modulation of intestinal and metabolic tissue immunity

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INTERNATIONAL JOURNAL OF OBESITY (2019)

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Obesity May Accelerate the Aging Process

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Crosstalk between the Akt/mTORC1 and NF-κB signaling pathways promotes hypoxia-induced pulmonary hypertension by increasing DPP4 expression in PASMCs

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TNF-α driven inflammation and mitochondrial dysfunction define the platelet hyperreactivity of aging

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BLOOD (2019)

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Hypothalamic Microinflammation Paradigm in Aging and Metabolic Diseases

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CELL METABOLISM (2019)

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Expanding the Organismal Proteostasis Network: Linking Systemic Stress Signaling with the Innate Immune Response

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The Metabolic Signature of Macrophage Responses

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Comparative Structure and Function Analysis of the RIG-I-Like Receptors: RIG-I and MDA5

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Challenges in Exosome Isolation and Analysis in Health and Disease

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Causative Links between Protein Aggregation and Oxidative Stress: A Review

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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2019)

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Inflammaging and Oxidative Stress in Human Diseases: From Molecular Mechanisms to Novel Treatments

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Longitudinal Changes in Fasting and Glucose-Stimulated GLP-1 and GIP in Healthy Older Subjects

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Inflamm-Aging Is Associated with Lower Plasma PTX3 Concentrations and an Impaired Capacity of PBMCs to Express hTERT following LPS Stimulation

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MEDIATORS OF INFLAMMATION (2019)

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Age-associated changes in human CD4+ T cells point to mitochondrial dysfunction consequent to impaired autophagy

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Aging progression of human gut microbiota

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BMC MICROBIOLOGY (2019)

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Cellular Senescence: Defining a Path Forward

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Defective induction of the proteasome associated with T-cell receptor signaling underlies T-cell senescence

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Polyamines Control eIF5A Hypusination, TFEB Translation, and Autophagy to Reverse B Cell Senescence

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MOLECULAR CELL (2019)

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Gut-associated IgA+ immune cells regulate obesity-related insulin resistance

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Rapamycin improves healthspan but not inflammaging in nfb1-/- mice

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AGING CELL (2019)

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Cell-free DNA as a biomarker of aging

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AGING CELL (2019)

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Biological Functions of Autophagy Genes: A Disease Perspective

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Cohesin-mediated NF-kappa B signaling limits hematopoietic stem cell self-renewal in aging and inflammation

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Chronic inflammation in the etiology of disease across the life span

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Sestrin2: Its Potential Role and Regulatory Mechanism in Host Immune Response in Diseases

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B Cell Dysfunction Associated With Aging and Autoimmune Diseases

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Autophagy balances inflammation in innate immunity

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AUTOPHAGY (2018)

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Sestrins are differentially expressed with age in the skeletal muscle of men: A cross-sectional analysis

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Faecalibacterium prausnitzii Produces Butyrate to Maintain Th17/Treg Balance and to Ameliorate Colorectal Colitis by Inhibiting Histone Deacetylase 1

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INFLAMMATORY BOWEL DISEASES (2018)

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The cGAS-cGAMP-STING pathway connects DNA damage to inflammation, senescence, and cancer

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Oxidative stress and cardiovascular disease: new insights

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Shedding light on the cell biology of extracellular vesicles

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ATF7 mediates TNF-α-induced telomere shortening

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TORC1 inhibition enhances immune function and reduces infections in the elderly

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Telomere Dysfunction Disturbs Macrophage Mitochondrial Metabolism and the NLRP3 Inflammasome through the PGC-1α/TNFAIP3 Axis

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Lipopolysaccharide-Induced Dephosphorylation of AMPK-Activated Protein Kinase Potentiates Inflammatory Injury via Repression of ULK1-Dependent Autophagy

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Minoru Koi et al.

WORLD JOURNAL OF GASTROINTESTINAL ONCOLOGY (2018)

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Association between insulin resistance and the development of cardiovascular disease

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Insulin Receptor-Mediated Stimulation Boosts T Cell Immunity during Inflammation and Infection

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mTORC Inhibitors as Broad-Spectrum Therapeutics for Age-Related Diseases

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Non-canonical Activation of the DNA Sensing Adaptor STING by ATM and IFI16 Mediates NF-κB Signaling after Nuclear DNA Damage

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Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1

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Inflammaging: a new immune-metabolic viewpoint for age-related diseases

Claudio Franceschi et al.

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Methionine Restriction Extends Lifespan in Progeroid Mice and Alters Lipid and Bile Acid Metabolism

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The Impact of the Microbiome on Immunosenescence

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mTORC1 Overactivation as a Key Aging Factor in the Progression to Type 2 Diabetes Mellitus

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Serine Phosphorylation by mTORC1 Promotes IRS-1 Degradation through SCFβ-TRCP E3 Ubiquitin Ligase

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Exosome-delivered microRNAs promote IFN-α secretion by human plasmacytoid DCs via TLR7

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The IKK-related kinase TBK1 activates mTORC1 directly in response to growth factors and innate immune agonists

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MicroRNA controls of cellular senescence

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Dietary rapamycin supplementation reverses age-related vascular dysfunction and oxidative stress, while modulating nutrient-sensing, cell cycle, and senescence pathways

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AGING CELL (2017)

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Coordination of DNA single strand break repair

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A prosurvival DNA damage-induced cytoplasmic interferon response is mediated by end resection factors and is limited by Trex1

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Aging-related Atg5 defect impairs neutrophil extracellular traps formation

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IMMUNOLOGY (2017)

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Fueling Inflamm-Aging through Mitochondrial Dysfunction: Mechanisms and Molecular Targets

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Key proteins and pathways that regulate lifespan

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Immunologic impact of the intestine in metabolic disease

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Proinflammatory Cytokines IL-6 and TNF-α Increased Telomerase Activity through NF-κB/STAT1/STAT3 Activation, and Withaferin A Inhibited the Signaling in Colorectal Cancer Cells

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MEDIATORS OF INFLAMMATION (2017)

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The Many Roles of Galectin-3, a Multifaceted Molecule, in Innate Immune Responses against Pathogens

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MEDIATORS OF INFLAMMATION (2017)

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Telomeres in cancer: tumour suppression and genome instability

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cGAS is essential for cellular senescence

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Inflammaging and 'Garb-aging'

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TRENDS IN ENDOCRINOLOGY AND METABOLISM (2017)

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Telomere Dynamics in Immune Senescence and Exhaustion Triggered by Chronic Viral Infection

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VIRUSES-BASEL (2017)

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Aged Gut Microbiota Contributes to Systemical Inflammaging after Transfer to Germ-Free Mice

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Pili-like proteins of Akkermansia muciniphila modulate host immune responses and gut barrier function

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Senescence-Inflammatory Regulation of Reparative Cellular Reprogramming in Aging and Cancer

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Putting p53 in Context

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Age-Associated Microbial Dysbiosis Promotes Intestinal Permeability, Systemic Inflammation, and Macrophage Dysfunction

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CELL HOST & MICROBE (2017)

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Writing, erasing and reading histone lysine methylations

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Vesicular Galectin-3 levels decrease with donor age and contribute to the reduced osteo-inductive potential of human plasma derived extracellular vesicles

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Diminished anabolic signaling response to insulin induced by intramuscular lipid accumulation is associated with inflammation in aging but not obesity

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Metabolic Control of Longevity

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Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic Programs in Trained Immunity

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Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype

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Gut Microbiota and Extreme Longevity

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Telomere Dysfunction in Nonalcoholic Fatty Liver Disease and Cryptogenic Cirrhosis

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Aging is associated with hypermethylation of autophagy genes in macrophages

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TGF-β triggers HBV cccDNA degradation through AID-dependent deamination

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TNF and ROS Crosstal in Inflammation

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Akkermansia muciniphila mediates negative effects of IFNγ on glucose metabolism

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Nucleic Acid-Targeting Pathways Promote Inflammation in Obesity-Related Insulin Resistance

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Telomere length in non-neoplastic gastric mucosa and its relationship to H. pylori infection, degree of gastritis, and NSAID use

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Regulation of the p19Arf/p53 pathway by histone acetylation underlies neural stem cell behavior in senescence-prone SAMP8 mice

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Activation-Induced Cytidine Deaminase Contributes to Pancreatic Tumorigenesis by Inducing Tumor-Related Gene Mutations

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Regulation of Obesity-Related Insulin Resistance with Gut Anti-inflammatory Agents

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Lifespan of mice and primates correlates with immunoproteasome expression

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Therapeutic targeting of autophagy in neurodegenerative and infectious diseases

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Androgen receptor modulates Foxp3 expression in CD4+CD25+Foxp3+ regulatory T-cells

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MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation

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Inflammation and cancer: advances and new agents

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The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4

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NAD+ in aging, metabolism, and neurodegeneration

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Hypothalamic microinflammation: a common basis of metabolic syndrome and aging

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DNA damage response (DDR) and senescence: shuttled inflamma-miRNAs on the stage of inflamm-aging

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Macrophage mTORC1 disruption reduces inflammation and insulin resistance in obese mice

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Circulating mitochondrial DNA increases with age and is a familiar trait: Implications for inflamm- aging

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Control of mitochondrial integrity in ageing and disease

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Inflammasome activation leads to Caspase-1-dependent mitochondrial damage and block of mitophagy

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mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity

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TSC1 controls macrophage polarization to prevent inflammatory disease

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Chronic inflammation induces telomere dysfunction and accelerates ageing in mice

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Mitochondria in Vascular Health and Disease

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ANNUAL REVIEW OF PHYSIOLOGY, VOL 75 (2013)

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The Hallmarks of Aging

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Sestrin2 integrates Akt and mTOR signaling to protect cells against energetic stress-induced death

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Aging and Insulin Resistance: Just Say iNOS

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IFN-α Inhibits Telomerase in Human CD8+ T Cells by Both hTERT Downregulation and Induction of p38 MAPK Signaling

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Succinate is an inflammatory signal that induces IL-1β through HIF-1α

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Cardiolipin externalization to the outer mitochondrial membrane acts as an elimination signal for mitophagy in neuronal cells

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AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network

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Activation-induced cytidine deaminase (AID) linking immunity, chronic inflammation, and cancer

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Inflammation-mediated genomic instability: roles of activation-induced cytidine deaminase in carcinogenesis

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Mitochondria: In Sickness and in Health

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mTOR Signaling in Growth Control and Disease

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Ageing as a Risk Factor for Disease

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Mechanisms of free radical-induced damage to DNA

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Inflammation-Associated Cancer Development in Digestive Organs: Mechanisms and Roles for Genetic and Epigenetic Modulation

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Cellular senescence and tumor suppressor gene p16

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Initial Pseudomonas aeruginosa treatment failure is associated with exacerbations in cystic fibrosis

Nicole Mayer-Hamblett et al.

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Mitochondrial quality control: an integrated network of pathways

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Expression of activation-induced cytidine deaminase in ulcerative colitis-associated carcinogenesis

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Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome

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DNA Damage Response

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COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY (2011)

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Inflammatory Processes Triggered by Helicobacter pylori Infection Cause Aberrant DNA Methylation in Gastric Epithelial Cells

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AMPK inhibition in health and disease

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CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY (2010)

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A Cytoplasmic ATM-TRAF6-cIAP1 Module Links Nuclear DNA Damage Signaling to Ubiquitin-Mediated NF-κB Activation

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Through Ageing, and Beyond: Gut Microbiota and Inflammatory Status in Seniors and Centenarians

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ER and aging-Protein folding and the ER stress response

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Loss of AMPK exacerbates experimental autoimmune encephalomyelitis disease severity

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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2009)

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Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion

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Activation of the NLRP3 inflammasome in dendritic cells induces IL-1β-dependent adaptive immunity against tumors

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Adenosine 5′-Monophosphate-Activated Protein Kinase Promotes Macrophage Polarization to an Anti-Inflammatory Functional Phenotype

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Inflammatory mechanisms in the regulation of insulin resistance

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Aberrant methylation of multiple tumor suppressor genes in aging liver, chronic hepatitis, and hepatocellular carcinoma

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Role of Reactive Oxygen Species in Tumor Necrosis Factor-alpha Induced Endothelial Dysfunction

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CURRENT HYPERTENSION REVIEWS (2008)

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Trends in oxidative aging theories

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Profile of histone lysine methylation across transcribed mammalian chromatin

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MOLECULAR AND CELLULAR BIOLOGY (2006)

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Nutrients suppress phosphatidylinositol 3-kinase/Akt signaling via raptor-dependent mTOR-mediated insulin receptor substrate 1 phosphorylation

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MOLECULAR AND CELLULAR BIOLOGY (2006)

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Human mitochondria-derived N-formylated peptides are novel agonists equally active on FPR and FPRL1, while Listeria monocytogenes-derived peptides preferentially activate FPR

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EUROPEAN JOURNAL OF IMMUNOLOGY (2005)

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Mismatch repair system and aging: Microsatellite instability in peripheral blood cells from differently aged participants

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JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES (2005)

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Ancient invasions: From endosymbionts to organelles

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Telomere erosion in memory T cells induced by telomerase inhibition at the site of antigenic challenge in vivo

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Butyrate inhibits inflammatory responses through NF kappa B inhibition: implications for Crohn's disease

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