H 2 S Supplementation and Augmentation: Approaches for Healthy Aging

Abstract

The ever-increasing percentages and absolute numbers of the world population over age 65 necessitates novel and effective measures to slow, counteract, and even reverse aging-related morbidities (ARMs). These interventions are traditionally disease specific and reactionary such as the use of chemotherapy for cancer and vasodilators for cardiovascular disease. Alternatively, momentum in the field has gained for proactive modalities that ultimately target the aging processes as a whole, thus slowing or eliminating the onset of all aging-related disorders. However, the later approach requires molecular and temporal mechanistic understandings of the aging process to be successful. Causes of aging are numerous; however, a central dogma is that aberrant and sustained production and exposure to reactive oxygen species (ROS) and free radicals drives the aging process, termed the free radical theory of aging. While still widely accepted, the free radical theory of aging has been amended in recent years, nonetheless, loss of redox homeostasis leads to a downward spiral of oxidative damage to macromolecules including DNA, lipids, and proteins resulting in the seemingly irreversible and self-perpetuating aspects of aging and senescence. Thus, investigating mechanisms to safely and effectively maintain redox homeostasis through (i) dampening the production of ROS and free radicals through modifying metabolic pathways, (ii) enhancing endogenous anti-oxidant processes, and/or (iii) applying these protective molecules exogenously, can ultimately provide therapeutic interventions against aging and ARMs. Here, we provide select examples in which hydrogen sulfide (H 2 S) itself, donor molecules, or the stimulation of its endogenous production by way of geroscience interventions were used to maintain cellular and organismal redox balance to extend lifespan, promote healthspan, and counter aging-related diseases. Additionally, we also provide examples in which enhanced endogenous H 2 S production and/or altered trans-sulfuration were found in models of exceptional longevity across evolutionary boundaries in which H 2 S impacts their specific aging trajectories.