Table 1.

Geroprotectors proven to upregulate autophagy and benefit healthspan and lifespan.

Activators	Mechanism of action	References
Macroautophagy
Target multiple cellular pathways (indirect regulation of macroautophagy)
Rapamycin	inhibition of mTORC1	(Bjedov et al., 2010; Schinaman et al., 2019)
Metformin	activation of AMPK, SIRT1; inhibition of mTORC1; CRM	(Kulkarni et al.,2020; Piskovatska et al., 2019)
Spermidine	through multiple mechanisms including inhibition of acetyltransferases, activation of mTORC1, induction of autophagy genes; CRM	(Eisenberg et al., 2016; Eisenberg et al., 2009; Yue et al., 2017)
Resveratrol	through different signaling pathways (AMPK, SIRT1, PGC-1α, and inhibition of mTOR); CRM	(Morselli et al., 2010)
Triethylenetetramine	protein deacetylation	(Pietrocola et al., 2020)
Sarcosine	activation of AMPK	(Walters et al., 2018)
Urolithin A	activation of PINK1-dependent and - independent mitophagy	(D’Amico et al., 2021)
NAD+	activation of mitophagy via Nix and ULK1	(Fang et al., 2019a)
Actinonin	activation of mitophagy via mitochondrial ribosomal and RNA decay pathway	(Fang et al., 2019b)
Doxycycline	activation of mitophagy	(Xing et al., 2017)
Target autophagy elements (direct regulation of macroautophagy)
Tat-Beclin-1 peptide	Beclin-1 activator	(Shoji-Kawata et al., 2013)
Compound C1	activation of TFEB	(Partridge et al., 2020)
CMA
Atypical RARα inhibitors	inhibition of a subprogram of the RARα signaling	(Bourdenx et al., 2021; Dong et al., 2021)
Humanin	Stabilizes substrate/receptor binding during translocation into lysosomes	(Gong et al., 2019)