H2S: A New Approach to Lifespan Enhancement and Healthy Ageing?

Abstract

Ageing, a progressive structural and functional decline, is considered to be a major risk factor for virtually all ageing-associated pathologies and disabilities, including Alzheimer's disease, Parkinson's disease, stroke, diabetes, atherosclerosis and certain cancers. Biogerontology research has now been largely directed towards finding novel drug targets to decelerate the ageing process and attain healthy ageing in order to delay the onset of all ageing-related diseases. H2S has been reported to exert vasodilatory, antioxidant, antiapoptotic and anti-inflammatory actions and has been shown to act as a signalling molecule, neuromodulator and cytoprotectant. Intriguingly, H2S has been reported to regulate cell cycle and survival in healthy cells which suggests that it may regulate cell fate and hence the ageing process. This chapter sets out to provide an overview of the current knowledge regarding the involvement of H2S in ageing, with a specific focus on the invertebrate model nematode C. elegans.

The role of hydrogen sulfide in aging and age-related pathologies

“…Aging is the progressive loss of physiological function which emerges when organisms grow older, with death of the organism as the ultimate, inevitable consequence [1, 3, 11]. Classic symptoms of human aging include graying and loss of hair, loss of hearing and eyesight, reduced fertility, immune system failure and loss of cognition [2].…”

“…A variety of molecular, biochemical and metabolic alterations occurring at the cellular level are thought to cause these functional losses [2]. For many years, aging research was largely focused on identifying the underlying cellular mechanisms as to find novel drug targets to modulate the aging process and to attain healthy aging by delaying the onset of age-related pathologies [3]. This approach has led to some unsubstantiated and opposing claims for potential cures as opposed to disease-oriented research [14].…”

“…As a consequence, the number of people experiencing age-related deterioration in health is rising, which will cause a great burden on the healthcare system [2]. The deterioration of the physiological integrity leads to an increased incidence of major human pathologies and increases the probability of death [1, 3]. Age remains the main risk factor for the development of debilitating and life-threatening, age-related pathologies such as cardiovascular disease, cancer, type 2 diabetes mellitus and neurodegenerative disorders including dementia [1–4].…”

“…Research on the aging process of sometimes distantly related model organisms – including yeast, nematodes, flies, mice and humans – led to the idea that lifespan regulation and aging are modulated by common and conserved mechanisms in many, if not all species [3, 5]. The discovery that exogenous hydrogen sulfide (H 2 S) prolongs the lifespan of the nematode Caenorhabditis elegans [6] has led to new insights in its role in health and disease, suggesting a relationship between H 2 S and aging [7].…”

Hydrogen Sulfide Inhibits Homocysteine-Induced Neuronal Senescence by Up-Regulation of SIRT1

“…In the brain, H 2 S is an important neuroprotective agent and has therapeutic potential in neurodegenerative diseases of aging, such as AD and PD [10,11]. Recently, H 2 S was identifiedas a new approach to Ivyspring International Publisher prolong lifespan [12]. H 2 S inhibits the production of mitochondrial ROS [13], decreases oxidative stress [14,15], and repairs DNA damage [16] to protect cells from senescence.…”