Anti-Aging Drugs and the Related Signal Pathways

Aging is a multifactorial biological process involving chronic diseases that manifest from the molecular level to the systemic level. From its inception to 31 May 2022, this study searched the PubMed, Web of Science, EBSCO, and Cochrane library databases to identify relevant research from 15,983 articles. Multiple approaches have been employed to combat aging, such as dietary restriction (DR), exercise, exchanging circulating factors, gene therapy, and anti-aging drugs. Among them, anti-aging drugs are advantageous in their ease of adherence and wide prevalence. Despite a shared functional output of aging alleviation, the current anti-aging drugs target different signal pathways that frequently cross-talk with each other. At present, six important signal pathways were identified as being critical in the aging process, including pathways for the mechanistic target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), nutrient signal pathway, silent information regulator factor 2-related enzyme 1 (SIRT1), regulation of telomere length and glycogen synthase kinase-3 (GSK-3), and energy metabolism. These signal pathways could be targeted by many anti-aging drugs, with the corresponding representatives of rapamycin, metformin, acarbose, nicotinamide adenine dinucleotide (NAD⁺), lithium, and nonsteroidal anti-inflammatory drugs (NSAIDs), respectively. This review summarized these important aging-related signal pathways and their representative targeting drugs in attempts to obtain insights into and promote the development of mechanism-based anti-aging strategies.