Anti-aging: senolytics or gerostatics (unconventional view).
aging
geroscience
hyperfunction theory
senolytics
sirolimus
Journal
Oncotarget
ISSN: 1949-2553
Titre abrégé: Oncotarget
Pays: United States
ID NLM: 101532965
Informations de publication
Date de publication:
31 Aug 2021
31 Aug 2021
Historique:
received:
07
06
2021
accepted:
05
07
2021
entrez:
10
9
2021
pubmed:
11
9
2021
medline:
11
9
2021
Statut:
epublish
Résumé
Senolytics are basically anti-cancer drugs, repurposed to kill senescent cells selectively. It is even more difficult to selectively kill senescent cells than to kill cancer cells. Based on lessons of cancer therapy, here I suggest how to exploit oncogene-addiction and to combine drugs to achieve selectivity. However, even if selective senolytic combinations will be developed, there is little evidence that a few senescent cells are responsible for organismal aging. I also discuss gerostatics, such as rapamycin and other rapalogs, pan-mTOR inhibitors, dual PI3K/mTOR inhibitors, which inhibit growth- and aging-promoting pathways. Unlike senolytics, gerostatics do not kill cells but slow down cellular geroconversion to senescence. Numerous studies demonstrated that inhibition of the mTOR pathways by any means (genetic, pharmacological and dietary) extends lifespan. Currently, only two studies demonstrated that senolytics (fisetin and a combination Dasatinib plus Quercetin) extend lifespan in mice. These senolytics slightly inhibit the mTOR pathway. Thus, life extension by these senolytics can be explained by their slight rapamycin-like (gerostatic) effects.
Identifiants
pubmed: 34504654
doi: 10.18632/oncotarget.28049
pii: 28049
pmc: PMC8416555
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
1821-1835Informations de copyright
Copyright: © 2021 Blagosklonny.
Déclaration de conflit d'intérêts
CONFLICTS OF INTEREST Authors have no conflicts of interest to declare.
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