Hydrogen sulfide in ageing, longevity and disease

Wilkie, Stephen E.; Borland, Gillian; Carter, Roderick N.; Morton, Nicholas M.; Selman, Colin

doi:10.1042/bcj20210517

Cited by 31 publications

(20 citation statements)

References 182 publications

(223 reference statements)

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“…Indeed, H 2 S can S-sulfhydrate proteins and higher protein S-sulfhydration levels induced by pharmacological or dietary interventions, lead to better resistance to oxidative stress and longer life. [38][39][40][41] Also, H 2 S generation has been linked with the beneficial effects of calorie restriction (sulfur amino acid restriction) on lifespan. 42,43 However, p53 was not directly targeted by H 2 S and the protein was not S-sulfhydrated in human endothelial cells in either this study or our previous investigation.…”

Section: Discussionmentioning

confidence: 99%

A novel role for cystathionine γ lyase in the control of p53: impact on endothelial senescence and metabolic reprograming

Leisegang

Looso

et al. 2022

Preprint

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Aims: Advanced age is unequivocally linked to the development of cardiovascular disease, however, the mechanisms leading to loss of endothelial cell regenerative capacity during aging remain poorly understood. Here we aimed to investigate novel mechanisms involved in endothelial cell senescence, that impact on endothelial cell transcription and the vascular repair response upon injury Methods and results: RNA sequencing of a unique collection of native endothelial cells from young and aged individuals, showed that aging (20 vs. 80 years) is characterized by p53-mediated reprogramming to promote the expression of senescence-associate genes. Molecular analysis revelead that p53 accumulated and acetylated in the nucleus of aged human endothelial cells to suppress glycolysis. Metabolic flux analysis identified an associated reduction in glucose uptake and ATP availability that inhibited the assembly of the telomerase complex, which was essential for proliferation. Nuclear translocation of p53 in aged endothelial cells was attributed to the loss of the vasoprotective enzyme, cystathionine gamma lyase (CSE), which physically anchored p53 in the cytosol. In mice, loss of endothelial cell CSE activated p53 and arrested vascular repair upon injury, while the AAV9 mediated re-expression of an active CSE mutant retained p53 in the cytosol, maintained endothelial glucose metabolism and proliferation, and prevented endothelial cell senescence. Adenoviral overexpression of CSE in human native aged endothelial cells maintained low p53 activity and re-activated telomerase to revert endothelial cell senescence. Conclusion: Our data identified the interaction between CSE and p53 as a promising target to preserve vascular regeneration during aging.

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Section: Discussionmentioning

confidence: 99%

A novel role for cystathionine γ lyase in the control of p53: impact on endothelial senescence and metabolic reprograming

Leisegang

Looso

et al. 2022

Preprint

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“…A previous review summarized the protective effects of H 2 S against almost all aging hallmarks, except for telomere attrition [ 5 ]. In addition, a series of review has highlighted this gaseous molecule as a potential preventive and therapeutic agent in aging and age-related diseases [ 20 , 39 ]; some of them focused on the effects of H 2 S on tissue-specific aging and its implications in associated diseases, particularly the cardiovascular system [ 40 ] and central nervous system [ 23 , 41 , 42 ]. Furthermore, there is a growing body of in vivo evidence to highlight the protective effects of H 2 S on the aging-associated changes in the kidney [ 43 , 44 ].…”

Section: Antioxidant Activities: a Conventional Anti-aging Paradigm O...mentioning

confidence: 99%

The Potential Implications of Hydrogen Sulfide in Aging and Age-Related Diseases through the Lens of Mitohormesis

Huynh

Wang

et al. 2022

Antioxidants

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The growing increases in the global life expectancy and the incidence of chronic diseases as a direct consequence have highlighted a demand to develop effective strategies for promoting the health of the aging population. Understanding conserved mechanisms of aging across species is believed helpful for the development of approaches to delay the progression of aging and the onset of age-related diseases. Mitochondrial hormesis (or mitohormesis), which can be defined as an evolutionary-based adaptive response to low-level stress, is emerging as a promising paradigm in the field of anti-aging. Depending on the severity of the perceived stress, there are varying levels of hormetic response existing in the mitochondria called mitochondrial stress response. Hydrogen sulfide (H2S) is a volatile, flammable, and toxic gas, with a characteristic odor of rotten eggs. However, H2S is now recognized an important gaseous signaling molecule to both physiology and pathophysiology in biological systems. Recent studies that elucidate the importance of H2S as a therapeutic molecule has suggested its protective effects beyond the traditional understanding of its antioxidant properties. H2S can also be crucial for the activation of mitochondrial stress response, postulating a potential mechanism for combating aging and age-related diseases. Therefore, this review focuses on highlighting the involvement of H2S and its sulfur-containing derivatives in the induction of mitochondrial stress response, suggesting a novel possibility of mitohormesis through which this gaseous signaling molecule may promote the healthspan and lifespan of an organism.

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“…Many studies have shown that H 2 S possesses significant biological activities including a role in aging [ [6] , [7] , [8] , [9] ]. For example, H 2 S reportedly protects cardiomyocytes against hypoxic injury in culture, and in animal models of cardiac and limb ischemia reperfusion injury [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Stable isotope dilution mass spectrometry quantification of hydrogen sulfide and thiols in biological matrices

et al. 2022

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Hydrogen sulfide in ageing, longevity and disease

Cited by 31 publications

References 182 publications

A novel role for cystathionine γ lyase in the control of p53: impact on endothelial senescence and metabolic reprograming

A novel role for cystathionine γ lyase in the control of p53: impact on endothelial senescence and metabolic reprograming

The Potential Implications of Hydrogen Sulfide in Aging and Age-Related Diseases through the Lens of Mitohormesis

Stable isotope dilution mass spectrometry quantification of hydrogen sulfide and thiols in biological matrices

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