Targeting cellular senescence based on interorganelle communication, multilevel proteostasis, and metabolic control.
Aging
/ genetics
Animals
Calcium Signaling
Caloric Restriction
/ methods
Cells, Cultured
Cellular Senescence
/ genetics
Gene Expression Regulation
Humans
Membrane Proteins
/ genetics
Mitochondria
/ genetics
Mitophagy
/ genetics
Oxidative Phosphorylation
Proteostasis
/ genetics
Proto-Oncogene Proteins
/ genetics
Reactive Oxygen Species
/ metabolism
Rejuvenation
/ physiology
TOR Serine-Threonine Kinases
/ genetics
Ubiquitin-Protein Ligases
/ genetics
RNA modification
calcium signaling homeostasis
caloric restriction mimetic
interorganellar connectivity
lysosome
mitochondria
mitophagy
proteostasis
senescence
translational control
Journal
The FEBS journal
ISSN: 1742-4658
Titre abrégé: FEBS J
Pays: England
ID NLM: 101229646
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
revised:
02
11
2020
received:
20
07
2020
accepted:
13
11
2020
pubmed:
18
11
2020
medline:
23
7
2021
entrez:
17
11
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33200494
doi: 10.1111/febs.15631
pmc: PMC7611050
mid: EMS123779
doi:
Substances chimiques
BNIP3 protein, human
0
Membrane Proteins
0
Proto-Oncogene Proteins
0
Reactive Oxygen Species
0
Ubiquitin-Protein Ligases
EC 2.3.2.27
parkin protein
EC 2.3.2.27
MTOR protein, human
EC 2.7.1.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
3834-3854Subventions
Organisme : Austrian Science Fund FWF
ID : J 4205
Pays : Austria
Organisme : Austrian Science Fund FWF
ID : P 30623
Pays : Austria
Organisme : Austrian Science Fund FWF
ID : P 31582
Pays : Austria
Organisme : Austrian Science Fund FWF
ID : W 1226
Pays : Austria
Informations de copyright
© 2020 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
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