期刊
FEBS JOURNAL
卷 288, 期 12, 页码 3834-3854出版社
WILEY
DOI: 10.1111/febs.15631
关键词
calcium signaling homeostasis; caloric restriction mimetic; interorganellar connectivity; lysosome; mitochondria; mitophagy; proteostasis; RNA modification; senescence; translational control
资金
- European integrated FP6-LIFESCIHEALTH project MiMAGE
- EU COST Action [CA15203 MitoEAGLE]
- Austrian Science Fund (FWF) [P31582, DK-MCD W1226]
- Tiroler Wissenschaftsfonds [ZAP746010]
- University of Innsbruck [281886, P7460-030-011]
- Erwin Schroedinger Abroad Fellowship [J4205-B27]
- Nikon Austria within the Nikon Center of Excellence, Graz
- MEFO-Graz
- Swedish Research Council Vetenskapsradet [2015-05468, 2019-05249]
- Knut and Alice Wallenberg foundation [2017.0091]
- Stiftelsen Olle Engkvist Byggmastare [194-0681]
- Austrian Science Fund (FWF)
- Herzfelder'sche Familienstiftung [P30623]
- Austrian Federal Ministry for Digital and Economic Affairs
- National Foundation for Research, Technology and Development
- Christian Doppler Research Association
- European Union [847681]
- EUREGIO Environment Food and Health project - European Region Tyrol-South-Tyrol-Trentino
- Swedish Research Council [2019-05249] Funding Source: Swedish Research Council
- Austrian Science Fund (FWF) [P30623] Funding Source: Austrian Science Fund (FWF)
- Marie Curie Actions (MSCA) [847681] Funding Source: Marie Curie Actions (MSCA)
Cellular senescence, a stable and irreversible cell division stoppage caused by severe damage and stress, is a key factor in aging in vertebrates. While compounds with senolytic or senostatic activity have been identified, their clinical effectiveness and specificity have yet to be fully established. Further research into targeting mechanisms related to mitochondria and other cellular functions may provide new opportunities to combat cellular senescence and promote healthy aging.
Cellular senescence, a stable cell division arrest caused by severe damage and stress, is a hallmark of aging in vertebrates including humans. With progressing age, senescent cells accumulate in a variety of mammalian tissues, where they contribute to tissue aging, identifying cellular senescence as a major target to delay or prevent aging. There is an increasing demand for the discovery of new classes of small molecules that would either avoid or postpone cellular senescence by selectively eliminating senescent cells from the body (i.e., 'senolytics') or inactivating/switching damage-inducing properties of senescent cells (i.e., 'senostatics/senomorphics'), such as the senescence-associated secretory phenotype. Whereas compounds with senolytic or senostatic activity have already been described, their efficacy and specificity has not been fully established for clinical use yet. Here, we review mechanisms of senescence that are related to mitochondria and their interorganelle communication, and the involvement of proteostasis networks and metabolic control in the senescent phenotype. These cellular functions are associated with cellular senescence in in vitro and in vivo models but have not been fully exploited for the search of new compounds to counteract senescence yet. Therefore, we explore possibilities to target these mechanisms as new opportunities to selectively eliminate and/or disable senescent cells with the aim of tissue rejuvenation. We assume that this research will provide new compounds from the chemical space which act as mimetics of caloric restriction, modulators of calcium signaling and mitochondrial physiology, or as proteostasis optimizers, bearing the potential to counteract cellular senescence, thereby allowing healthy aging.
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