Table 1.
Pharmacological agent/Compounds | Mechanism of action/Impact on autophagy | Effect on health and lifespan | References |
---|---|---|---|
Acetylsalicylic acid and derivatives (C8-SA) | Anti-inflammation effect, autophagy induction by inhibition of EP300/p300; Activation of mitochondria unfolded protein response |
Increase lifespan of genetically heterogeneous male mice; Increase lifespan in worms |
[86, 87] |
Alpha-ketoglutarate (AKG) | Reduce mTOR activation by inhibiting ATP synthase | Prolong lifespan in worms and flies, but reduces reproduction | [144] |
Cannabidiol | SIRT1-dependent autophagy induction | Prolong lifespan and increased neuronal health in worms | [145] |
Flavonoid 4,4′-dimethoxychalcone (DMC) | Induces autophagy in an mTOR-independent manner, but depends on GATA transcription factors | Increase lifespan of yeast, worm and flies | [146] |
Ganoderma lucidum, dietary supplements | Induce autophagy in an mTOR-dependent manner and stress resistance by reducing the levels of Fibrilarin 1(FIB-1) and LGG-1 | Increase longevity in worms and human cells | [147] |
Glucosamine (GlcN) | Promotes autophagy via an mTOR-independent manner | Extend lifespan in nematodes | [148, 149] |
Nordihydroguaiaretic acid (NDGA) | Inhibition of EP300/p300 and activation of autophagy | Increase lifespan in flies and mice | [150] |
Pyrroloquinoline quinone (PQQ) | Activation of autophagy via Insulin/IGF1 signaling pathway | Extends lifespan in worms by 31% | [151] |
Metformin | Promote autophagy via AMPK | Extends lifespan in nematodes and mice | [152] |
Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), dietary supplements | Increase autophagy and mitophagy | Increase lifespan in worms, flies and mice | [153] |
Rapamycin | Autophagy induction by direct inhibition of mTOR | Extends lifespan in worms, flies and mice | [154] |
Resveratrol | SIRT1-dependent autophagy induction | Improve longevity in yeast, worms, flies and mice | [155] |
SGLT2 Inhibitors | Mimics calorie restriction by inducing glycosuria. Promotes upregulation of AMPK, SIRT1 and mTOR inhibition | Appear to be a promising treatment extending longevity and reduce oxidative stress | [156] |
Shatavarin IV | Via eat-2 activation promotes autophagy by promoting the expression of autophagy-related genes expression in an mTOR-dependent manner | On dietary restriction prolonged lifespan | [157] |
Spermidine | Autophagy induction, reduce inflammation, lipid metabolism, regulation of cell growth, proliferation and cell death | Prolong median lifespan of female mice | [158] |
Verapamil | Inhibition of calcineurin activity and activation of autophagy | Prolong lifespan, improve health span and delay senescence in worms | [159] |