Table 2:

List of anti-aging drugs with cardiovascular benefits involving autophagy induction

Drug	Species	Lifespan & cardiovascular response	Possible mechanisms	Reference
Rapamycin	Rodents, human (Hutchinson-Gilford progeria syndrome)	Prolongs lifespan, reverses age-related oxidative stress, cardiac and vascular dysfunction, reverses cellular phenotype of fibroblasts from children	Activates AMPK, inhibits mTOR, S6 kinase and ULK1 phosphorylation, induces autophagy, clears progerin through autophagy, promotes mitochondrial biogenesis.	[26, 88-90]
Resveratrol	Rodents, human, Yeast, C. elegans, Drosophila	Prolongs lifespan, improves cardiac and vascular function as well as mitochondrial number but not glucose metabolism in aging	Activates AMPK and Sirtuins, mimics calorie restriction, affects acetylproteome, promotes lipolysis and attenuates lipogenesis	[91-93]
Metformin	Rodents, human aortic endothelial cells, C. elegans, Drosophila	Prolongs lifespan, improves Physiological and metabolic parameters in aging (glucose tolerance, exercise capacity and cardiac function), delays endothelial senescence via mitochondrial biogenesis/function	Activation of AMPK, H3K79 methylation, inhibits mTOR, reduces hyperglycemia and hyperinsulinemia and alleviates insulin resistance	[94, 95]
Nicotinamide derivatives, specific CD38 inhibitor 78c	Rodents, human	Improves healthspan but not lifespan, reverses age-related NAD+ decline and improves cardiac function in natural and accelerate aging	Stimulates autophagy and mitophagy, increases NAD+ levels, activation of Sirtuins, AMPK and poly (ADP ribose) polymerases (PARPs)	[59, 96]
Spermidine	Rodents, human, yeast nematodes and flies	Prolongs lifespan, improves healthspan, reduces cardiac hypertrophy and remodeling, preserves diastolic function in aging, reduces blood pressure and incidence of cardiovascular disease and cancer mortality	Induces autophagy, Mitophagy and mitochondrial respiration, inhibits histone acetyltransferases, inflammation, oxidative stress, affects glutathione metabolism, lipid metabolism	[60, 61, 63, 93]
OPN inhibitor Agelastatin A	Rodents	Rescues cardiac aging and induces a selective fibroblast senescence	Modulates fibroblast senescence by osteopontin (OPN) production.	[10]
Fibroblast growth factor 21 (FGF21)	Rodents, C. elegans	Improves healthspan and extends lifespan; alleviates age-related metabolic disorders, including atherosclerosis, obesity, type 2 diabetes	Activates AMPK, Autophagy and anti-inflammation	[65]
Urolithin A	Rodents and C. elegans	Prolongs lifespan, improves healthspan, exercise capacity and mitochondrial function	Stimulates mitophagy, prevents accumulation of dysfunctional mitochondria	[67]
N-Acetyl-glucosamine	C. elegans	Extends mean lifespan	Enhances autophagy, ER-Associated protein degradation, and proteasomal activity	[68]
Curcumin	Human	Improves vascular endothelial function in healthy middle-aged and older adults.	Increased nitric oxide (NO) bioavailability and reduced oxidative stress	[71]
b-Guani-dinopropionic acid	Drosophila melanogaster	Prolongs lifespan	Activates autophagy by AMPK-Atg1 signaling pathway	[69]
Kallistatin	Rodents, C. elegans	Extends lifespan, reduces vascular senescence and aging.	MicroRNA-34a-Sirt1-dependent	[72, 73]
Melatonin	Cardiac progenitor cells	Antagonizes premature senescence of cardiac progenitor cells	H19/miR-675/USP10-depndent pathway	[70]