Aging is a biological process that is linked to a functional decline, ultimately resulting in death. Large interindividual differences exist in terms of life- and healthspan, representing life expectancy and the number of years spent in the absence of major diseases, respectively. The genetic and molecular mechanisms that are involved in the regulation of the aging process, and those that render age the main risk factor for many diseases are still poorly understood. Nevertheless, a growing number of compounds have been put forward to affect this process. However, for scientists and laypeople alike, it is difficult to separate facts from fiction, and hype from hope. In this review, we discuss the currently pursued pharmacological anti-aging approaches. These are compared to non-pharmacological interventions, some of which confer powerful effects on health and well-being, in particular an active lifestyle and exercise. Moreover, functional parameters and biological clocks as well as other molecular marks are compared in terms of predictive power of morbidity and mortality. Then, conceptual aspects and roadblocks in the development of anti-aging drugs are outlined. Finally, an overview on current and future strategies to mitigate age-related pathologies and the extension of life- and healthspan is provided. Abstract figure legend Modulation of the human aging process. Aging leads to a functional decline with increased frailty and morbidity, ultimately resulting in death. This process is affected by the genetic setup, epigenetic predisposition, and random events, leading to large interindividual differences in regard to health, well-being and life expectancy. Exercise, diet and other lifestyle-based interventions as well as societal measures can help to maximize the chance for healthy aging. Proposed drugs, cellular, epigenetic, and other non-pharmacological approaches such as caloric restriction await validation for safe and efficacious application in human geroprotection. This article is protected by copyright. All rights reserved.

Keywords: aging; exercise; healthspan; lifespan; longevity; rapamycin; rejuvenation; reprogramming; senolytics.

PMID: 36114675 DOI: 10.1113/JP282887

Drugs, clocks and exercise in aging: hype and hope, facts and fiction