☆ 4.8 Review

Hallmarks of aging: An expanding universe

CELL (2023)

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Review Cell Biology

Acetylation in the regulation of autophagy

Yinfeng Xu et al.

Summary: This review summarizes the importance of acetylation modifications in the regulation of autophagy and their regulatory roles on multiple autophagy proteins. Acetylation regulates autophagy initiation, autophagosome formation, and transcriptional regulation by targeting core protein complexes and key regulatory molecules.

AUTOPHAGY (2023)

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Review Neurosciences

Sirtuins, a key regulator of ageing and age-related neurodegenerative diseases

Vidhi Bhatt et al.

Summary: Sirtuins are a class of proteins dependent on NAD(＋), found in various organisms from bacteria to humans. They play important roles in metabolism and aging, and have neuroprotective effects by modulating apoptosis, DNA repair, protein aggregation, and inflammatory processes. This review discusses the role of Sirtuins in aging and age-related neurodegenerative diseases, as well as their therapeutic potential and the use of inhibitors/activators in altering disease pathology.

INTERNATIONAL JOURNAL OF NEUROSCIENCE (2023)

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Review Cell Biology

Meta-hallmarks of aging and cancer

Carlos Lopez-Otin et al.

Summary: Both aging and cancer share similar characteristics, known as hallmarks, some of which are common metahallmarks. While some aging hallmarks suppress cancer development, others have context-dependent effects. The relationship between aging-associated nutrient-sensing and cancer-related cellular metabolism alterations is complex. Understanding the interplay between aging and cancer has significant implications for cancer morbidity and mortality in the elderly and for therapeutic strategies.

CELL METABOLISM (2023)

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Article Cell Biology

DNA methylation signatures in Blood DNA of Hutchinson-Gilford Progeria syndrome

Yosra Bejaoui et al.

Summary: In this study, the researchers conducted a genome-wide methylation analysis on blood DNA samples from patients with progeroid laminopathies. They found DNA methylation alterations at specific CpG sites and regions, and identified possible pathways/mechanisms involved in the accelerated aging process of progeroid laminopathies. They also observed significant differences in methylation patterns between different subtypes of progeroid laminopathies.

AGING CELL (2022)

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Article Cell Biology

Sex- and strain-specific effects of mitochondrial uncoupling on age-related metabolic diseases in high-fat diet-fed mice

Leigh Goedeke et al.

Summary: Mild mitochondrial uncoupling has potential as an anti-aging therapy, but chronic ingestion of uncouplers has unwanted side effects. A controlled-release mitochondrial protonophore (CRMP) was developed and tested in aged high-fat diet-fed mice. The results showed that CRMP reduced hepatic lipid content, improved insulin resistance, and protected against neoplastic disorders, demonstrating the potential of liver-directed mitochondrial uncouplers in promoting healthy aging.

AGING CELL (2022)

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Review Pathology

Molecular Pathology of Laminopathies

Ji-Yeon Shin et al.

Summary: Nuclear envelope is composed of various components and mutations in genes encoding these components can lead to laminopathies, a group of diseases that selectively affect different tissues or organs. The mechanisms underlying these diseases are still unclear and current hypotheses focus on the impact of nuclear envelope alterations on gene expression and cellular mechanics.

ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE (2022)

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Article Neurosciences

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 Cardiac & Cardiovascular Systems

The role of cellular senescence in cardiac disease: basic biology and clinical relevance

Mozhdeh Mehdizadeh et al.

Summary: This review discusses the role of cellular senescence in cardiac disease, outlines therapeutic strategies for targeting senescence, and considers potential implications for improving the management of patients with heart disease. The complex senescence-associated secretory phenotype (SASP) of senescent cells has important effects on cell and tissue biology. Future research is needed to better understand the precise role of senescent cells in various cardiac pathologies and develop strategies for preventing their accumulation.

NATURE REVIEWS CARDIOLOGY (2022)

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Review Biotechnology & Applied Microbiology

Pharmacological targeting of endoplasmic reticulum stress in disease

Stefan J. Marciniak et al.

Summary: Research on drug-like molecules targeting ER stress and UPR has made progress, but limitations still exist. Understanding these limitations is crucial for the development of these molecules into therapeutic drugs.

NATURE REVIEWS DRUG DISCOVERY (2022)

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Review Endocrinology & Metabolism

Mitochondrial and metabolic dysfunction in ageing and age-related diseases

Joao A. Amorim et al.

Summary: Organismal ageing leads to cellular function loss and systemic deterioration, making individuals more vulnerable to death. Mitochondria play a crucial role not only as energy suppliers but also in the development of ageing-associated diseases. Evidence suggests that ageing and age-related diseases are closely related to imbalances in energy supply and demand, which can be alleviated through various interventions.

NATURE REVIEWS ENDOCRINOLOGY (2022)

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Article Multidisciplinary Sciences

Caloric restriction in humans reveals immunometabolic regulators of health span

O. Spadaro et al.

Summary: Research indicates that a 14% caloric restriction in healthy individuals can improve immune cell generation and is associated with pathways regulating mitochondrial bioenergetics, anti-inflammatory responses, and longevity. The inhibition of the platelet activating factor acetyl hydrolase gene Pia2g7 may mediate the effects of reducing inflammation and extending healthy lifespan.

SCIENCE (2022)

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Article Multidisciplinary Sciences

Mitochondrial protein import determines lifespan through metabolic reprogramming and de novo serine biosynthesis

Eirini Lionaki et al.

Summary: Inhibition of mitochondrial protein import reduces mitochondrial abundance and extends lifespan in Caenorhabditis elegans. This effect is mediated by activation of glycolysis and de novo serine biosynthesis. The study also shows that mitochondrial chaperone induction is not essential for lifespan extension.

NATURE COMMUNICATIONS (2022)

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Review Cell Biology

Autophagy in metabolism and quality control: opposing, complementary or interlinked functions?

Vojo Deretic et al.

Summary: Autophagy is both a metabolic process and a quality control process, involving specific receptors that selectively remove various intracellular targets. It is regulated by master regulators of cellular metabolism such as MTOR and AMPK, making the system responsive to amino acid and glucose starvation.

AUTOPHAGY (2022)

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Article Cell Biology

Enhanced autophagy in Becn1(F121A/F121A) knockin mice counteracts aging-related neural stem cell exhaustion and dysfunction

Chenran Wang et al.

Summary: The study demonstrates that enhanced autophagy in aging neural stem cells can protect them from exhaustion, promote neurogenesis, and improve olfactory function in aged animals.

AUTOPHAGY (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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Article Cell Biology

Multi-omic rejuvenation of naturally aged tissues by a single cycle of transient reprogramming

Dafni Chondronasiou et al.

Summary: A single period of OSKM expression can induce epigenetic, transcriptomic, and metabolomic changes towards a younger configuration in multiple tissues.

AGING CELL (2022)

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Article Cell Biology

Biological mechanisms of aging predict age-related disease co-occurrence in patients

Helen C. Fraser et al.

Summary: This study found that interventions in the aging process can confer resistance to multiple age-related diseases in laboratory animals. By analyzing literature abstracts and clinical data, the researchers discovered associations between age-related diseases and aging mechanisms in humans. They also identified specific mechanisms that are associated with diverse age-related diseases. This suggests that targeting these mechanisms could potentially prevent multimorbidity.

AGING CELL (2022)

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Article Cell Biology

Reducing ER stress with chaperone therapy reverses sleep fragmentation and cognitive decline in aged mice

Jennifer M. Hafycz et al.

Summary: Understanding age-related changes in health is crucial as the aging population expands. Disrupted sleep and impaired cognition are two prominent behavioral changes that occur with age. Using a mouse model of aging, researchers found that supplementing chaperone levels reduces endoplasmic reticulum stress and improves sleep quality and memory. These findings have important implications for the development of therapies to improve health and lifespan in the elderly population.

AGING CELL (2022)

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Review Genetics & Heredity

Genome-Wide Analysis of Human Long Noncoding RNAs: A Provocative Review

Chris P. Ponting et al.

Summary: This article discusses the contribution of long noncoding RNAs (lncRNAs) to human biology from a genome-wide perspective. The majority of evidence suggests that most lncRNA transcript models are transcriptional noise or have minor regulatory roles, with only a few lncRNAs playing a central role in human development, physiology, or behavior. These important lncRNAs tend to be spliced and better conserved but lack a simple syntax relating sequence to structure and mechanism, making them resistant to simple categorization.

ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS (2022)

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Article Cell Biology

The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson's disease

Brage Brakedal et al.

Summary: In this study, we found that oral intake of nicotinamide riboside (NR) in Parkinson's disease (PD) patients was safe and increased cerebral NAD levels, leading to altered cerebral metabolism and mild clinical improvement. NR also upregulated processes related to mitochondrial, lysosomal, and proteasomal function in blood cells and/or skeletal muscle, and decreased the levels of inflammatory cytokines.

CELL METABOLISM (2022)

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Article Cell & Tissue Engineering

Heterochronic parabiosis induces stem cell revitalization and systemic rejuvenation across aged tissues

Shuai Ma et al.

Summary: This study provides a comprehensive framework to explore aging and rejuvenating trajectories at single-cell resolution, revealing cellular and molecular programs that instruct systemic revitalization by blood-borne factors. Specifically, it identified hematopoietic stem and progenitor cells (HSPCs) as one of the most responsive cell types to young blood exposure, initiating a continuum of cell state changes and restoring a youthful transcriptional regulatory program and cell-cell communications in HSPCs.

CELL STEM CELL (2022)

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Article Gastroenterology & Hepatology

Protective Role of Spermidine in Colitis and Colon Carcinogenesis

Alain P. Gobert et al.

Summary: The study demonstrates that Spd treatment can reduce colitis and carcinogenesis, reversing the effects of SMOX deficiency on colitis and CAC, reducing tumor development, and modulating the microbiome.

GASTROENTEROLOGY (2022)

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Article Biochemistry & Molecular Biology

Fecal microbiota transplantation from young donor mice improves ovarian function in aged mice

Li Xu et al.

Summary: This study investigates the relationship between gut microbiota and ovarian aging by transplanting fecal microbiota from young into aged mice. The results show that the transplantation improves the gut microbiota composition, increases anti-inflammatory cytokine levels, and enhances ovarian function, suggesting that fecal microbiota transplantation could be a potential strategy for delaying ovarian aging.

JOURNAL OF GENETICS AND GENOMICS (2022)

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Article Multidisciplinary Sciences

Somatic genomic changes in single Alzheimer's disease neurons

Michael B. Miller et al.

Summary: This study analyzed single-cell whole-genome sequencing data from the prefrontal cortex and hippocampus of individuals with Alzheimer's disease, revealing an increase in somatic DNA alterations. These alterations, driven by distinct processes and nucleotide changes, potentially implicate nucleotide oxidation. The accumulation of DNA alterations in Alzheimer's disease may lead to genomic damage to neurons and impair their function.

NATURE (2022)

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Article Multidisciplinary Sciences

Somatic mutation rates scale with lifespan across mammals

Alex Cagan et al.

Summary: Through whole-genome sequencing of 208 intestinal crypts from 56 individuals, this study reveals that somatic mutation in mammals is dominated by endogenous mutational processes, and mutational signatures in different species show similarities to those in humans, though with variations in relative contribution. The study also finds a strong inverse relationship between somatic mutation rate and species lifespan, suggesting that somatic mutation rates are evolutionarily constrained and may contribute to aging.

NATURE (2022)

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Article Multidisciplinary Sciences

Molecular hallmarks of heterochronic parabiosis at single-cell resolution

Robert Palovics et al.

Summary: Slowing or reversing biological ageing can have significant implications for disease risk reduction and maintaining vitality. However, there is still much to explore regarding the effectiveness of interventions on various cell types and molecular pathways. Through single-cell RNA sequencing on 20 organs, this study identified specific cell types, such as adipose mesenchymal stromal cells, haematopoietic stem cells, and hepatocytes, that respond to young and aged blood. Additionally, it was found that young blood not only reverses established ageing patterns but also activates new gene sets, particularly highlighting the role of mitochondrial function in rejuvenation.

NATURE (2022)

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Article Multidisciplinary Sciences

Environmental factors shaping the gut microbiome in a Dutch population

R. Gacesa et al.

Summary: This study analyzed the gut microbiome of 8,208 individuals from the Netherlands and found that the microbiome is primarily shaped by the environment and cohabitation. Only about 6.6% of microbial taxa are heritable, while around 48.6% of taxa are significantly influenced by cohabitation. Additionally, the study identified numerous associations between the microbiome and health, diet, socioeconomic factors, and early-life and current exposome.

NATURE (2022)

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Article Genetics & Heredity

Single-cell analysis of somatic mutations in human bronchial epithelial cells in relation to aging and smoking

Zhenqiu Huang et al.

Summary: Single-cell whole-genome sequencing of proximal bronchial basal cells revealed that somatic mutation frequencies increase with age and are higher in smokers compared to never-smokers. The mutation frequencies plateaued after a certain level of smoking dose, suggesting intrinsic mechanisms to limit mutation burden. Known lung cancer-defined mutation signatures correlated with both age and smoking status.

NATURE GENETICS (2022)

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Article Biochemistry & Molecular Biology

Cross-cohort gut microbiome associations with immune checkpoint inhibitor response in advanced melanoma

Karla A. Lee et al.

Summary: An analysis of metagenomic sequencing of stool samples reveals the association between gut microbiome and response to immune checkpoint blockade therapy in melanoma patients. However, there is limited consistency in the microbiome-based signatures across different populations. Future studies should consider larger sample sizes and examine the complex interplay between clinical factors and the gut microbiome.

NATURE MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Intestinal microbiota signatures of clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1

John A. McCulloch et al.

Summary: An integrated analysis of microbiome and host cell transcriptional data in patients with melanoma treated with anti-PD-1 therapy reveals new associations between streptococcus species and immune-related adverse effects. The study also identifies consistent microbiome associations with clinical outcomes. The results show that baseline microbiota composition is optimally associated with clinical outcome one year after treatment initiation. Meta-analysis and bioinformatic analyses reveal that bacteria associated with favorable response are within the Actinobacteria phylum and Lachnospiraceae/Ruminococcaceae families of Firmicutes. Gram-negative bacteria, on the other hand, are associated with an inflammatory host intestinal gene signature and unfavorable outcome. Two different microbial signatures, enriched for Lachnospiraceae spp. and Streptococcaceae spp., are associated with favorable and unfavorable clinical response, respectively, along with distinct immune-related adverse effects. Supervised learning algorithms consistently predict treatment outcomes in all cohorts, despite heterogeneity between cohorts. The study provides valuable insights into the complex interaction between gut microbiome and response to cancer immunotherapy, paving the way for future research.

NATURE MEDICINE (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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Review Gastroenterology & Hepatology

Akkermansia muciniphila: paradigm for next-generation beneficial microorganisms

Patrice D. Cani et al.

Summary: This article reviews the discovery of Akkermansia muciniphila and its association with health and disease. Studies have shown that A. muciniphila can improve health through various mechanisms and comparisons are made with other next-generation beneficial microorganisms.

NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY (2022)

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Review Genetics & Heredity

Making sense of the ageing methylome

Kirsten Seale et al.

Summary: This article reviews the changes in DNA methylation during aging and the statistical tools used to quantify them. It also explores the evidence linking DNA methylation to aging phenotypes and strategies for extending healthspan and lifespan. Finally, it discusses theories on the mechanistic causes of epigenetic aging.

NATURE REVIEWS GENETICS (2022)

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Review Physiology

TELOMERE-MEDIATED LUNG DISEASE

Jonathan K. Alder et al.

PHYSIOLOGICAL REVIEWS (2022)

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Article Multidisciplinary Sciences

Advanced age increases frequencies of de novo mitochondrial mutations in macaque oocytes and somatic tissues

Barbara Arbeithuber et al.

Summary: Duplex sequencing technology reveals the accumulation of mtDNA mutations in somatic tissues and germline cells of primates as they age. The frequency of these mutations significantly increases in liver and muscle tissues with age, while it stabilizes in oocytes of older animals after 9 years of age.

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

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Article Multidisciplinary Sciences

Protective role of chaperone-mediated autophagy against atherosclerosis

Julio Madrigal-Matute et al.

Summary: The study found that reduced activity of chaperone-mediated autophagy (CMA) exacerbates the progression of atherosclerosis. Conversely, up-regulated CMA in a genetic mouse model leads to lower vulnerability to atherosclerotic challenges. Thus, CMA could be an attractive therapeutic target against cardiovascular diseases.

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

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Article Multidisciplinary Sciences

A hypothalamic pathway for Augmentor α-controlled body weight regulation

Mansoor Ahmed et al.

Summary: This study investigates the physiological roles of Aug alpha and Aug beta in regulating body weight and resistance to obesity. The experiments reveal the involvement of Alk-driven cancers in the neural pathway controlling body weight, offering potential therapeutic opportunities for metabolic diseases and cancer.

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

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Article Multidisciplinary Sciences

Circadian alignment of early onset caloric restriction promotes longevity in male C57BL/6J mice

Victoria Acosta-Rodriguez et al.

Summary: Research shows that the interval of fasting and circadian alignment of feeding are important factors in extending lifespan under CR; nighttime CR can alleviate inflammation and metabolic pathway damage caused by aging; circadian interventions promote longevity.

SCIENCE (2022)

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Article Cell Biology

miR-188-3p targets skeletal endothelium coupling of angiogenesis and osteogenesis during ageing

Wen-Zhen He et al.

Summary: A recent study has shown that a specific bone capillary subtype, known as type H vessels, is involved in both angiogenesis and osteogenesis. However, the number of type H vessels in bone tissue decreases with age, and the underlying mechanism for this reduction is unknown. In this study, researchers found that microRNA-188-3p (miR-188-3p) is involved in this process. Upregulation of miR-188-3p in skeletal endothelium negatively regulates the formation of type H vessels during aging. Further experiments revealed that miR-188 inhibits type H vessel formation by directly targeting integrin beta 3 in endothelial cells. These findings suggest that miR-188-3p is a key regulator of type H vessel formation and may be a potential therapeutic target for preventing bone loss and accelerating bone regeneration.

CELL DEATH & DISEASE (2022)

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Article Cell Biology

In vivo partial cellular reprogramming enhances liver plasticity and regeneration

Tomoaki Hishida et al.

Summary: Mammals have limited regenerative capacity, but inducing specific factor expression can enhance liver regeneration. This study provides a new avenue for tissue regeneration.

CELL REPORTS (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 Multidisciplinary Sciences

Premature aging in mice with error-prone protein synthesis

Dimitri Shcherbakov et al.

Summary: The main source of error in gene expression lies in the decoding of messenger RNA by the ribosome. Experimental evidence from a mouse model suggests that translation errors can lead to reduced life span and premature onset of aging-related phenotypes, providing a link between translational accuracy, life span, and aging-related phenotypes in mammals.

SCIENCE ADVANCES (2022)

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Article Cardiac & Cardiovascular Systems

TET2-Driven Clonal Hematopoiesis and Response to Canakinumab An Exploratory Analysis of the CANTOS Randomized Clinical Trial

Eric C. Svensson et al.

Summary: This study investigated whether individuals with CHIP have a greater reduction in cardiovascular events in response to IL-1 beta neutralization therapy.

JAMA CARDIOLOGY (2022)

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Article Cardiac & Cardiovascular Systems

Fine-Tuning Cardiac Insulin-Like Growth Factor 1 Receptor Signaling to Promote Health and Longevity

Mahmoud Abdellatif et al.

Summary: This study suggests a biphasic relationship between insulin-like growth factor 1 receptor (IGF1R) signaling and cardiac health. Higher IGF1R signaling in young mice leads to declining cardiac function and shorter lifespan, while lower IGF1R signaling improves cardiac function and extends lifespan in aging mice.

CIRCULATION (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

Small-molecule activation of OGG1 increases oxidative DNA damage repair by gaining a new function

Maurice Michel et al.

Summary: We describe a small molecule that interacts with OGG1, increases enzyme activity and generates a new lyase function. This molecule controls catalytic activity and alters the repair process of oxidative DNA damage. The findings may have therapeutic applications in various diseases and aging.

SCIENCE (2022)

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Article Cell Biology

LINE-1 RNA causes heterochromatin erosion and is a target for amelioration of senescent phenotypes in progeroid syndromes

Francesco Della Valle et al.

Summary: Research has shown that the accumulation of L1 RNA in progeroid syndromes leads to the loss of heterochromatin and onset of aging phenotypes. Depleting L1 RNA using specific antisense oligonucleotides restores heterochromatin homeostasis, reverses DNA methylation age, and counteracts the expression of genes associated with senescence. Systemic delivery of antisense oligonucleotides rescues tissue histophysiology and increases the lifespan of a progeria mouse model.

SCIENCE TRANSLATIONAL MEDICINE (2022)

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Article Biochemistry & Molecular Biology

Diverse partial reprogramming strategies restore youthful gene expression and transiently suppress cell identity

Antoine E. Roux et al.

Summary: Partial pluripotent reprogramming can reverse features of aging in mammalian cells but may temporarily suppress somatic identity programs. Different subsets of the Yamanaka Factors can restore youthful expression and suppress somatic identity to varying degrees. A multipotent reprogramming strategy inspired by amphibian regeneration can restore youthful expression in myogenic cells.

CELL SYSTEMS (2022)

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Article Biochemistry & Molecular Biology

A rare human centenarian variant of SIRT6 enhances genome stability and interaction with Lamin A

Matthew Simon et al.

Summary: A variant of the enzyme SIRT6 (centSIRT6) may contribute to human longevity by improving genome maintenance through enhanced mADPr activity and an enhanced interaction with LMNA. This variant is a stronger suppressor of LINE1 retrotransposons, stimulates DNA double-strand break repair more effectively, and kills cancer cells more robustly compared to the wild-type SIRT6. Surprisingly, centSIRT6 exhibits weaker deacetylase activity but stronger mADPr activity.

EMBO JOURNAL (2022)

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Article Cell Biology

In vivo cyclic induction of the FOXM1 transcription factor delays natural and progeroid aging phenotypes and extends healthspan

Rui Ribeiro et al.

Summary: The FOXM1 gene plays a crucial role in maintaining cellular homeostasis and has the potential to delay cellular and organismal aging, thereby mitigating aging-related pathologies.

NATURE AGING (2022)

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Article Cell Biology

In vivo partial reprogramming alters age-associated molecular changes during physiological aging in mice

Kristen C. Browder et al.

Summary: Partial reprogramming can restore a youthful epigenetic signature to aging cells and extend the lifespan of a premature aging mouse model. Long-term partial reprogramming has rejuvenating effects on different tissues and at the organismal level. The extent of the beneficial effects depends on the duration of the treatment. The rejuvenating effects are associated with a reversion of the epigenetic clock and changes in metabolism and gene expression.

NATURE AGING (2022)

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Article Cell Biology

The relationship between epigenetic age and the hallmarks of aging in human cells

Sylwia Kabacik et al.

Summary: Epigenetic clocks are age estimators based on methylation values at specific CpGs in the genome. This study investigates the relationship between epigenetic aging and the previously identified aging hallmarks, and finds associations with nutrient sensing, mitochondrial activity, and stem cell composition.

NATURE AGING (2022)

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Article Cell Biology

Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults

Anurag Singh et al.

Summary: The study demonstrates that the administration of Urolithin A can significantly improve muscle strength, aerobic endurance, and physical performance, while reducing inflammation and enhancing mitochondrial efficiency.

CELL REPORTS MEDICINE (2022)

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Review Geriatrics & Gerontology

The Complicated Nature of Somatic mtDNA Mutations in Aging

Monica Sanchez-Contreras et al.

Summary: Mitochondria are the main source of energy in cells and play a potential role in age-related tissue dysfunction. However, the exact contribution of mtDNA mutations to aging and its associated pathologies is still debated. In this review, the authors summarize the current understanding of somatic mtDNA mutations, including their timing, location, and mechanisms during aging. They also evaluate the limitations in our knowledge and highlight emerging technologies that can advance our understanding of somatic mtDNA mutagenesis in the aging process.

FRONTIERS IN AGING (2022)

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Review Immunology

The role of T cells in age-related diseases

Elisa Carrasco et al.

Summary: T cells play a crucial role in age-related diseases, potentially leading to the failure of immune tolerance mechanisms and tissue damage. Targeting T cells could offer new therapeutic opportunities to enhance resilience to age-related diseases.

NATURE REVIEWS IMMUNOLOGY (2022)

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Review Pharmacology & Pharmacy

Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span

Paul D. Robbins et al.

Summary: Senescence is a signaling mechanism activated in stressed cells to prevent proliferation of damaged cells, leading to chronic sterile inflammation and age-related diseases. Senescent cells accumulate with age and in diseased anatomical sites, making them a logical therapeutic target. Senotherapeutics, a new class of drugs, selectively kill senescent cells or suppress their disease-causing phenotypes, showing promising results in preclinical studies and clinical trials.

ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 61, 2021 (2021)

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Review Geriatrics & Gerontology

ATP-dependent chromatin remodelers in ageing and age-related disorders

Pynskhem Bok Swer et al.

Summary: Ageing is characterized by disturbances in various cellular mechanisms, including genomic instability and epigenetic alterations, with chromatin remodelers playing a key role in regulating processes such as DNA repair and transcription. The link between dietary restriction and chromatin remodelers in regulating age-related processes is also discussed for potential future intervention studies.

BIOGERONTOLOGY (2021)

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Article Genetics & Heredity

A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome, a genetic disorder of mitochondrial cardiolipin metabolism

W. Reid Thompson et al.

Summary: In an interventional clinical trial in BTHS, daily administration of Elamipretide led to improvement in BTHS symptoms, including significant improvements in 6MWT and BTHS-SA at 36 weeks.

GENETICS IN MEDICINE (2021)

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Article Geriatrics & Gerontology

Effect of rapamycin on aging and age-related diseases-past and future

Ramasamy Selvarani et al.

Summary: Rapamycin has shown potential to extend lifespan and treat age-related diseases in mice. Research should continue to focus on the effects of rapamycin in aging physiology and diseases, and bringing it into clinical applications.

GEROSCIENCE (2021)

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Article Cell Biology

Growth hormone receptor gene disruption in mature-adult mice improves male insulin sensitivity and extends female lifespan

Silvana Duran-Ortiz et al.

Summary: Studies suggest that reducing growth hormone action can enhance healthy lifespan. In adult mice, disrupted GH action resulted in sexual dimorphic effects, with males showing enhanced insulin sensitivity and reduced tumors, while females exhibited increased lifespan and reduced glucose and oxidative stress.

AGING CELL (2021)

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Article Cell Biology

Dietary citrate supplementation enhances longevity, metabolic health, and memory performance through promoting ketogenesis

Shou-Zen Fan et al.

Summary: The study shows that dietary supplementation with citrate can reduce energy status and extend lifespan in fruit flies, with implications on AMPK, TOR, and ketogenesis at the molecular level. Additionally, mice fed a high-fat diet supplemented with citrate or β-OHB demonstrate improved metabolic health and memory. These findings suggest that dietary citrate supplementation may be a beneficial intervention for age-related dysfunction in the future.

AGING CELL (2021)

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Article Cell Biology

Rejuvant®, a potential life-extending compound formulation with alpha-ketoglutarate and vitamins, conferred an average 8 year reduction in biological aging, after an average of 7 months of use, in the TruAge DNA methylation test

Oleksandr Demidenko et al.

Aging-US (2021)

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Article Cell Biology

Increasing skeletal muscle carnitine content in older individuals increases whole-body fat oxidation during moderate-intensity exercise

Carolyn Chee et al.

Summary: Increasing muscle total carnitine content in older men can enhance fat oxidation and intramyocellular lipid utilization during exercise. However, this intervention did not lead to improvements in resting insulin-stimulated whole-body or skeletal muscle glucose disposal. Further research is needed to explore the potential metabolic benefits of carnitine supplementation in older adults with impaired lipid turnover.

AGING CELL (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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Review Biochemistry & Molecular Biology

Hallmarks of Health

Carlos Lopez-Otin et al.

Summary: Health is more than just the absence of disease; it involves a combination of organizational and dynamic features that maintain physiology. Biological causes of health include spatial compartmentalization, maintenance of homeostasis, and adequate responses to stress. Disruption of these features can lead to pathogenic processes.

CELL (2021)

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Review Biochemistry & Molecular Biology

Cytoplasmic DNA: sources, sensing, and role in aging and disease

Karl N. Miller et al.

Summary: This article summarizes the key role of endogenous cytoplasmic DNA (cytoDNA) species in inflammation, emphasizing the similarities and differences between different cytoDNAs, as well as their underlying molecular mechanisms of formation and function.

CELL (2021)

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Article Cell Biology

Fasting-mimicking diet blocks triple-negative breast cancer and cancer stem cell escape

Giulia Salvadori et al.

Summary: The study demonstrates that a fasting-mimicking diet activates starvation escape pathways in TNBC cells and reduces stemness markers in CSCs, leading to decreased cell numbers and improved mouse survival. Additionally, the diet activates different survival/growth pathways in differentiated cancer cells, which can be targeted by drugs to promote tumor regression.

CELL METABOLISM (2021)

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Article Immunology

Comprehensive Profiling of an Aging Immune System Reveals Clonal GZMK+ CD8+ T Cells as Conserved Hallmark of Inflammaging

Denis A. Mogilenko et al.

Summary: This study characterized age-associated alterations in immune cells across multiple mouse organs and identified a distinct population of age-associated GZMK-expressing CD8(+) T cells. These Taa cells, highly clonal with specific features, were found to be a potential target to address age-associated dysfunctions of the immune system. In humans, proportions of the circulating GZMK(+) CDE3(+) T cell population that shares signatures with mouse Taa cells also increased during healthy aging.

IMMUNITY (2021)

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Article Cell Biology

The transcription factor code in iPSC reprogramming

Weixian Deng et al.

Summary: The understanding of iPSC reprogramming has provided insights into the mechanisms that safeguard somatic cell identity, drive epigenetic reprogramming, and underlie cell fate specification in vivo. The combinatorial action of TFs has emerged as the key mechanism for the direct and indirect effects of reprogramming factors that induce the remodelling of the enhancer landscape. The interplay of TFs in iPSC reprogramming also yields trophectoderm-and extraembryonic endoderm-like cell populations, uncovering an intriguing plasticity of cell states and opening new avenues for exploring cell fate decisions during early embryogenesis.

CURRENT OPINION IN GENETICS & DEVELOPMENT (2021)

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Article Multidisciplinary Sciences

In vivo base editing rescues Hutchinson-Gilford progeria syndrome in mice

Luke W. Koblan et al.

Summary: Using adenine base editor (ABE), researchers successfully corrected the pathogenic mutation in fibroblasts from children with Hutchinson-Gilford progeria syndrome, mitigating RNA mis-splicing, reducing progerin levels, and correcting nuclear abnormalities. In vivo base editing with AAV9 encoding ABE in transgenic mice resulted in substantial, durable correction of the mutation, restoration of normal RNA splicing, and improvement of vascular pathology, ultimately extending the lifespan of the mice. These findings demonstrate the potential of in vivo base editing as a treatment for genetic diseases.

NATURE (2021)

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Article Multidisciplinary Sciences

Restoring metabolism of myeloid cells reverses cognitive decline in ageing

Paras S. Minhas et al.

Summary: Ageing is characterized by chronic pro-inflammatory responses that affect various aspects of health, including the brain. The study shows that in ageing mice, myeloid cell bioenergetics are suppressed in response to increased signalling by the lipid messenger prostaglandin E-2 (PGE(2)), leading to maladaptive pro-inflammatory responses. By inhibiting myeloid EP2 signalling, it is possible to reverse cognitive ageing and restore youthful immune functions.

NATURE (2021)

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Article Multidisciplinary Sciences

Chaperone-mediated autophagy sustains haematopoietic stem-cell function

Shuxian Dong et al.

Summary: Activation of hematopoietic stem cells involves molecular adaptations, with Chaperone-Mediated Autophagy (CMA) playing a role in sustaining HSC function and declining with age. Restoring old HSC functionality through CMA activation suggests it may be a promising therapeutic target for conditions like aging or stem-cell transplantation.

NATURE (2021)

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Article Biochemistry & Molecular Biology

Translation elongation rate varies among organs and decreases with age

Maxim Gerashchenko et al.

Summary: The study developed a labeling-free method to measure organ- and celltype-specific translation elongation rates, and found significant differences in elongation rates among different mouse organs. Additionally, the study revealed that the elongation rate decreases with age, indicating tight regulation of translation at the level of elongation of nascent polypeptide chains.

NUCLEIC ACIDS RESEARCH (2021)

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Article Multidisciplinary Sciences

Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders

Yoshikazu Johmura et al.

Summary: Research has shown that senescent cells rely on glutaminolysis for survival, and inhibiting this process can induce senolysis. Lysosomal membrane damage lowers intracellular pH in senescent cells, inducing KGA expression, leading to glutaminolysis, and ultimately producing ammonia to neutralize low pH and improve cell survival.

SCIENCE (2021)

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Article Cell Biology

A genome-wide CRISPR-based screen identifies KAT7 as a driver of cellular senescence

Wei Wang et al.

Summary: Understanding the genetic and epigenetic factors of cellular senescence is crucial for developing interventions to slow aging. CRISPR-Cas9-based screens identified genes like KAT7 that alleviate senescence in accelerated aging models, and lentiviral vectors encoding Cas9/sg-Kat7 were effective in alleviating cellular aging and extending lifespan.

SCIENCE TRANSLATIONAL MEDICINE (2021)

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Article Multidisciplinary Sciences

MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis

Joseph C. Reynolds et al.

Summary: Mitochondrial-encoded MOTS-c can enhance physical performance and healthspan in mice by regulating nuclear genes, skeletal muscle metabolism, and myoblast adaptation to metabolic stress. Late-life intermittent MOTS-c treatment can increase physical capacity and healthspan in mice, and exercise can induce endogenous MOTS-c expression in humans, showing beneficial effects on metabolism and overall physiologic fitness in aging organisms.

NATURE COMMUNICATIONS (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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Article Cell Biology

Protein signatures of centenarians and their offspring suggest centenarians age slower than other humans

Paola Sebastiani et al.

Summary: Using samples from the New England Centenarian Study, researchers characterized the serum proteome of centenarians, their offspring, and age-matched controls. They identified protein signatures associated with longer survival in centenarians and younger individuals and found similarities in aging markers between centenarians and short-lived cohorts. The study provides specific circulating biomarkers of healthy aging and longevity, suggesting potential mechanisms to prolong health and support longevity.

AGING CELL (2021)

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Article Pharmacology & Pharmacy

Lonafarnib: First Approval

Sohita Dhillon

Summary: Lonafarnib is an orally active farnesyltransferase inhibitor developed for the treatment of hepatitis D virus infections, progeria, and progeroid laminopathies. It works by inhibiting farnesyltransferase to prevent the accumulation of specific proteins in the nucleus and cellular cytoskeleton, leading to its approval for Hutchinson-Gilford Progeria Syndrome and processing-deficient progeroid laminopathies in the USA.

DRUGS (2021)

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Article Cell Biology

Strategies for late phase preclinical and early clinical trials of senolytics

Erin O. Wissler Gerdes et al.

Summary: Accumulation of senescent cells is associated with various age-related and chronic diseases, making them potential targets for intervention. Preclinical and early clinical trials with senolytics have shown promising results, but more clinical trials are needed to further evaluate their efficacy across different aging and disease models.

MECHANISMS OF AGEING AND DEVELOPMENT (2021)

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Article Multidisciplinary Sciences

Circadian autophagy drives iTRF-mediated longevity

Matt Ulgherait et al.

Summary: Studies have shown that intermittent Time-restricted feeding (iTRF) extends the lifespan of fruit flies and delays aging markers, with circadian-regulated autophagy playing a crucial role in this process.

NATURE (2021)

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Review Cell Biology

Shaping human telomeres: from shelterin and CST complexes to telomeric chromatin organization

Ci Ji Lim et al.

Summary: The recently determined structures of telomere maintenance protein complexes shed new light on the regulation of telomere DNA replication and end-capping, and how mutations in their encoding genes may affect their functions. Dysfunctional telomere maintenance can lead to diseases, highlighting the importance of understanding telomere biology for human health.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2021)

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Review Clinical Neurology

Applying genomic and transcriptomic advances to mitochondrial medicine

William L. Macken et al.

Summary: This article discusses the current genetic testing approach for primary mitochondrial diseases and the opportunities for increased use of whole-genome NGS. It also explores the expanding applications of RNA sequencing.

NATURE REVIEWS NEUROLOGY (2021)

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Article Cell Biology

Cap-independent translation: A shared mechanism for lifespan extension by rapamycin, acarbose, and 17α-estradiol

Ziqian Shen et al.

Summary: The study suggests that rapamycin and acarbose can prevent age-related declines in cap-independent translation (CIT) target proteins in both sexes, while 17 alpha-estradiol has a similar effect only in males. The activity of mTORC1 is blocked by rapamycin, acarbose, and 17 alpha-estradiol in age-related increases. The increase in METTL3 activity and CIT-dependent proteins may represent a shared pathway for both long-lived mutant mice and drug-induced lifespan extension in mice.

AGING CELL (2021)

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Article Biochemistry & Molecular Biology

Chaperone-mediated autophagy prevents collapse of the neuronal metastable proteome

Mathieu Bourdenx et al.

Summary: This study reveals that loss of neuronal CMA leads to altered neuronal function, changes in the neuronal proteome, and proteotoxicity, while enhancing CMA can ameliorate pathology in Alzheimer's disease mouse models. Functional CMA is essential for maintaining neuronal proteostasis and protecting against neurodegenerative diseases.

CELL (2021)

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Article Biochemistry & Molecular Biology

MicroRNA-455-3p improves synaptic, cognitive functions and extends lifespan: Relevance to Alzheimer's disease

Subodh Kumar et al.

Summary: The study found that miR-455-3p has a protective role in mouse models, prolonging lifespan, improving cognitive function, and enhancing mitochondrial and synaptic activities. Conversely, depletion of miR-455-3p leads to impaired physiological functions and shortened lifespan.

REDOX BIOLOGY (2021)

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Article Multidisciplinary Sciences

An aged immune system drives senescence and ageing of solid organs

Matthew J. Yousefzadeh et al.

Summary: Researchers found that aged immune system could lead to attrition and senescence of specific immune cell populations, driving systemic ageing.

NATURE (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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Article Multidisciplinary Sciences

Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women

Mihoko Yoshino et al.

Summary: The study demonstrates that NMN supplementation can enhance insulin sensitivity, insulin signaling, and remodeling in women with prediabetes who are overweight or obese, improving their metabolic function.

SCIENCE (2021)

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Article Cell Biology

eIF5A hypusination, boosted by dietary spermidine, protects from premature brain aging and mitochondrial dysfunction

YongTian Liang et al.

Summary: Mitochondrial function declines with age in the brain, and supplementing spermidine levels can delay this decline. The levels of hypusinated eIF5A decline with age in the Drosophila brain, but can be boosted by dietary spermidine. Attenuating eIF5A hypusination affects brain mitochondrial respiration and accelerates aging in locomotion and memory formation in adult Drosophilae, indicating it may be a potential diagnostic and therapeutic avenue for age-induced cognitive decline and neurodegeneration.

CELL REPORTS (2021)

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Article Biology

A TORC1-histone axis regulates chromatin organisation and non-canonical induction of autophagy to ameliorate ageing

Yu-Xuan Lu et al.

Summary: Research shows that inhibition of mTORC1 by rapamycin increases the expression of histones H3 and H4 in intestinal enterocytes of Drosophila, leading to improved intestinal health and extended longevity. This finding suggests that the mTORC1-histone axis may be partially conserved in mammals, potentially offering new targets for anti-ageing interventions.

ELIFE (2021)

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Review Cell Biology

Fibroageing: An ageing pathological feature driven by dysregulated extracellular matrix-cell mechanobiology

Moises Selman et al.

Summary: Ageing is a complex biological process involving multiple factors that lead to a decline in physiological functions and an increased risk of chronic diseases. Inflammageing and fibrotic pathways play key roles in age-related morbidities and the accumulation of extracellular matrix in the elderly. The concept of Fibroageing suggests that stiff ECM and activation of fibrotic positive feedback loops contribute to various age-related alterations.

AGEING RESEARCH REVIEWS (2021)

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Article Cell Biology

The antagonistic pleiotropy of insulin-like growth factor 1

William B. Zhang et al.

Summary: The study found two generalized patterns in the relationship between serum IGF-1 levels and clinical disease: IGF-1 interacts with age to modify risk in a manner consistent with antagonistic pleiotropy, and the association between IGF-1 and risk is generally U-shaped. These effects were remarkably consistent across a wide range of conditions, except for a more uniformly positive relationship between IGF-1 and cancer.

AGING CELL (2021)

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Article Cell Biology

Youthful and age-related matreotypes predict drugs promoting longevity

Cyril Statzer et al.

Summary: Researchers found that most anti-aging compounds that extend lifespan in model organisms also alter extracellular matrix gene expression in human cell lines. By using this observation along with age-stratified human transcriptomes, they screened for potential geroprotective drug candidates and developed a novel tool using prolonged collagen expression as a marker for evaluating longevity in Caenorhabditis elegans. They identified and validated several new compounds, like tretinoin, chondroitin sulfate, and hyaluronic acid, for their ability to restore collagen homeostasis and increase lifespan.

AGING CELL (2021)

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Article Cell Biology

Type I Interferon signaling controls the accumulation and transcriptomes of monocytes in the aged lung

Shanti S. D'Souza et al.

Summary: Research has shown that physiological lung aging leads to increased interferon signaling and elevated chemokine concentrations, which exacerbate monocyte infiltration into the lung parenchyma, including a novel subset dependent on type-1 interferon signaling. Treatment with anti-IFNAR1 neutralizing antibodies can rapidly eradicate this subset of monocytes, reduce airway chemokine concentrations, and suppress the accumulation of monocytes in the aged lung parenchyma.

AGING CELL (2021)

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Article Biochemistry & Molecular Biology

Polyamine metabolism is a central determinant of helper T cell lineage fidelity

Daniel J. Puleston et al.

Summary: Polyamine synthesis plays a critical role in T cell activation and differentiation, regulating CD4(+) T cells' function and epigenetic remodeling. Studies have revealed the significance of polyamine metabolism in controlling the fate of T-H cell subsets, with deficiency leading to aberrant expression of cytokines and transcription factors.

CELL (2021)

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Article Cell Biology

Increased fidelity of protein synthesis extends lifespan

Victoria Eugenia Martinez-Miguel et al.

Summary: The loss of proteostasis is a fundamental process driving aging, and the accuracy of translation significantly affects proteostasis. A rare amino acid substitution found in certain hyperthermophilic archaea, when introduced into other organisms, improves translation accuracy, heat shock resistance, and longevity. Anti-aging drugs such as rapamycin, Torin1, and trametinib reduce translation errors and extend organismal longevity, particularly in mutants with high translation accuracy due to this unique substitution in the RPS23 protein.

CELL METABOLISM (2021)

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Review Biochemistry & Molecular Biology

Autophagy in major human diseases

Daniel J. Klionsky et al.

Summary: Autophagy is crucial for maintaining cellular and organismal homeostasis, and dysfunction in autophagy is implicated in the pathogenesis of major human disorders across various organ systems.

EMBO JOURNAL (2021)

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Article Medicine, Research & Experimental

Inhibition of the NLRP3 inflammasome improves lifespan in animal murine model of Hutchinson-Gilford Progeria

Alvaro Gonzalez-Dominguez et al.

Summary: This study showed increased expression of NLRP3 inflammasome components in HGPS skin fibroblasts and lymphoblasts, as well as in hearts and livers of Zmpste24(-/-) mice. Inhibiting the NLRP3 inflammasome with MCC950 improved cellular phenotype, extended lifespan of progeroid animals, and reduced inflammation, suggesting a potential therapeutic approach for HGPS.

EMBO MOLECULAR MEDICINE (2021)

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Article Biochemistry & Molecular Biology

Chondroitin 6-sulphate is required for neuroplasticity and memory in ageing

Sujeong Yang et al.

Summary: Perineuronal nets (PNNs), containing chondroitin sulphate proteoglycans on neuronal surfaces, play a role in neuroplasticity and memory. Age-related reduction of chondroitin 6-sulphates (C6S) in PNNs leads to increased inhibition. Manipulating CS composition of PNNs can restore neuroplasticity and memory deficits in aged mice, with a focus on the importance of C6S in memory and neuroplasticity.

MOLECULAR PSYCHIATRY (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

Novel bile acid biosynthetic pathways are enriched in the microbiome of centenarians

Yuko Sato et al.

Summary: Centenarians have a unique gut microbiome enriched in microorganisms capable of producing specific bile acids, including a previously undescribed isoform. The specific bile acid isoalloLCA exhibits potent antimicrobial effects against Gram-positive multidrug-resistant pathogens, suggesting a potential role in reducing infection risk.

NATURE (2021)

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Article Multidisciplinary Sciences

Reversible reprogramming of cardiomyocytes to a fetal state drives heart regeneration in mice

Yanpu Chen et al.

Summary: Research shows that expression of OSKM genes in adult cardiomyocytes can induce these cells to dedifferentiate, conferring regenerative capacity to the heart. This short-term dedifferentiation and reprogramming can ameliorate myocardial damage and facilitate heart regeneration.

SCIENCE (2021)

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Article Multidisciplinary Sciences

Counteracting age-related VEGF signaling insufficiency promotes healthy aging and extends life span

M. Grunewald et al.

Summary: The study reveals that insufficiency in vascular endothelial growth factor (VEGF) signaling may drive physiological aging across multiple organ systems in aged mice, while increasing VEGF signaling can prevent this and lead to improved organ function, extended lifespan, and better overall health.

SCIENCE (2021)

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Review Biochemistry & Molecular Biology

Impact of the Natural Compound Urolithin A on Health, Disease, and Aging

Davide D'Amico et al.

Summary: Urolithin A is a natural compound derived from gut bacteria, with benefits such as enhancing cellular health and reducing inflammation. Preclinical studies have shown that UA plays a crucial role in protecting muscles, brain, joints, and other organs from aging and age-related conditions.

TRENDS IN MOLECULAR MEDICINE (2021)

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Article Cell Biology

Regeneration, Rejuvenation, and Replacement: Turning Back the Clock on Tissue Aging

Thomas A. Rando et al.

Summary: Aging is the progressive loss of cell and tissue function leading to organ dysfunction and disease, with stem cells playing a crucial role in maintaining tissue homeostasis and repair. Restoring stem cell function can be achieved through strategies such as environmental interventions, heterochronic approaches, and cellular reprogramming.

COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY (2021)

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Article Multidisciplinary Sciences

Restoration of energy homeostasis by SIRT6 extends healthy lifespan

A. Roichman et al.

Summary: The study demonstrates that overexpression of SIRT6 extends lifespan in mice and optimizes energy homeostasis in old age, delaying frailty and preserving healthy aging. Aged SIRT6-transgenic mice maintain hepatic glucose output and glucose homeostasis through improved utilization of two major gluconeogenic precursors, lactate, and glycerol.

NATURE COMMUNICATIONS (2021)

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Article Nutrition & Dietetics

Lactobacillus plantarum GKM3 Promotes Longevity, Memory Retention, and Reduces Brain Oxidation Stress in SAMP8 Mice

Shih-Wei Lin et al.

Summary: The study revealed that the probiotic Lactobacillus plantarum GKM3 has significant effects in delaying aging, alleviating age-related cognitive impairment, and reducing oxidative stress.

NUTRIENTS (2021)

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Article Cell Biology

The prolyl-isomerase PIN1 is essential for nuclear Lamin-B structure and function and protects heterochromatin under mechanical stress

Francesco Napoletano et al.

Summary: PIN1 is a crucial protein in maintaining heterochromatin, preventing neurodegeneration and cognitive defects caused by TE mobilization. Its mechanism is conserved from Drosophila to humans.

CELL REPORTS (2021)

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Article Oncology

IGF1 receptor inhibition amplifies the effects of cancer drugs by autophagy and immune-dependent mechanisms-

Qi Wu et al.

Summary: The study identified PPP as a potent autophagy inducer by inhibiting the tyrosine kinase activity of IGF1R. In animal models, PPP improved the therapeutic efficacy of chemoimmunotherapy, but this effect was lost when tumors were insensitive to PPP or autophagy-incompetent.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2021)

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Article Medicine, Research & Experimental

Ketone body β-hydroxybutyrate is an autophagy-dependent vasodilator

Cameron G. McCarthy et al.

Summary: Autophagy is associated with longevity and can reverse and prevent vascular deterioration linked to aging and cardiovascular diseases. The biosynthesis of beta-hydroxybutyrate (beta HB) is autophagy-dependent and causes vasodilation through potassium channels rather than Gpr109a. Chronic high-salt diet negatively impacts beta HB biosynthesis and hepatic autophagy, but reconstitution of beta HB availability can prevent diet-induced endothelial dysfunction.

JCI INSIGHT (2021)

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Article Clinical Neurology

The unfolded protein response in amyotrophic later sclerosis: results of a phase 2 trial

Eleonora Dalla Bella et al.

Summary: Strong evidence supports the role of endoplasmic reticulum stress in ALS pathogenesis, with guanabenz showing promise in reducing neuronal death and prolonging survival through targeting this pathway. A randomized trial showed that higher doses of guanabenz were effective in preventing disease progression, particularly in ALS patients with bulbar onset symptoms. Further research on molecules targeting the unfolded protein response pathway without the side effects of guanabenz is needed for larger trials.

BRAIN (2021)

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Article Cell Biology

Telomerase reverse transcriptase preserves neuron survival and cognition in Alzheimer's disease models

Hong Seok Shim et al.

Summary: The research found that deficiency of telomerase reverse transcriptase (TERT) affects neuronal expression and accumulation of amyloid-beta in the brain, while maintaining normal levels of TERT helps reduce amyloid-beta accumulation and preserve cognitive function. Furthermore, the interaction between TERT, beta-catenin, and RNA polymerase II at gene promoters leads to the upregulation of gene networks governing synaptic signaling and learning processes.

NATURE AGING (2021)

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Article Cell Biology

Senolytic vaccination improves normal and pathological age-related phenotypes and increases lifespan in progeroid mice

Masayoshi Suda et al.

Summary: The study identified GPNMB as a target for senolytic therapy, and immunization against GPNMB improved normal and pathological phenotypes associated with aging, extending the lifespan of aging mice.

NATURE AGING (2021)

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Review Cell Biology

Molecular damage in aging

Vadim N. Gladyshev et al.

Summary: This Review discusses the concept of molecular damage in aging, from theoretical models to experimental approaches, highlighting the central role of damage accumulation in the aging process. It emphasizes the importance of measuring multiple types of damage and the development of omics approaches to study the role of molecular damage in aging.

NATURE AGING (2021)

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Article Endocrinology & Metabolism

Fasting drives the metabolic, molecular and geroprotective effects of a calorie-restricted diet in mice

Heidi H. Pak et al.

Summary: The study demonstrates that prolonged fasting plays a crucial role in the effects of calorie restriction on insulin sensitivity, fuel utilization, and aging in mice. Simply reducing caloric intake alone is not enough to replicate all these effects, highlighting the importance of daily prolonged fasting in regulating metabolic health and longevity.

NATURE METABOLISM (2021)

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Article Cell Biology

Modulating the integrated stress response to slow aging and ameliorate age-related pathology

Maxime J. Derisbourg et al.

Summary: This article discusses the importance of coordinating various stress signaling pathways for healthy aging, with a focus on the key role of the integrated stress response (ISR) in the protein homeostasis network. Studies have shown an increase in ISR activity with age, suggesting a potential role of ISR in modulating the aging process.

NATURE AGING (2021)

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Article Cell Biology

Microbiota from young mice counteracts selective age-associated behavioral deficits

Marcus Boehme et al.

Summary: The study demonstrates that rejuvenation of the gut microbiome by fecal microbiota transplantation from young mice can reverse aging-induced differences in the immune system, metabolome, and transcriptome, and improve specific cognitive deficits.

NATURE AGING (2021)

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Review Genetics & Heredity

Origins of human disease: the chrono-epigenetic perspective

Edward Saehong Oh et al.

Summary: Epigenetics enriches human disease studies with new interpretations, but identifying causal mechanisms has been challenging. Recent findings in intra-individual and cyclical epigenetic variation present new opportunities, and the temporality in the epigenome may help integrate diverse disease studies.

NATURE REVIEWS GENETICS (2021)

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Article Cell Biology

Short and dysfunctional telomeres sensitize the kidneys to develop fibrosis

Sarita Saraswati et al.

Summary: Accumulation of short telomeres is a hallmark of aging and can sensitize kidneys to develop fibrosis by influencing the EMT program. Deletion of Trf1 in kidneys also leads to fibrosis and EMT activation. This study shows that short and dysfunctional telomeres enhance the genetic program associated with epithelial-to-mesenchymal transition in two mouse models of kidney fibrosis.

NATURE AGING (2021)

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Article Endocrinology & Metabolism

Gut microbiome pattern reflects healthy ageing and predicts survival in humans

Tomasz Wilmanski et al.

Summary: The study finds that as individuals age, the gut microbiome becomes increasingly unique, with this uniqueness strongly associated with microbially produced amino acid derivatives in the bloodstream. Healthy older individuals continue to show microbial drift towards a unique compositional state, while less healthy individuals do not. Retaining high levels of Bacteroides dominance or having a low gut microbiome uniqueness measure predicts decreased survival in a 4-year follow-up.

NATURE METABOLISM (2021)

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Review Physiology

SIRT6, A MAMMALIAN DEACYLASE WITH MULTITASKING ABILITIES

Andrew R. Chang et al.

PHYSIOLOGICAL REVIEWS (2020)

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Article Cell Biology

NLRP3 inflammasome suppression improves longevity and prevents cardiac aging in male mice

Fabiola Marin-Aguilar et al.

AGING CELL (2020)

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Article Cell Biology

Short-term interleukin-37 treatment improves vascular endothelial function, endurance exercise capacity, and whole-body glucose metabolism in old mice

Dov B. Ballak et al.

AGING CELL (2020)

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