Abstract
Recent evidence suggests that hydrogen sulfide (H2S) has cytoprotective and anti-aging effects. However, the mechanisms for such properties are not fully understood. Here, we show that the expression of the main H2S producing enzyme, CBS, and production of H2S are coordinately diminished in replicative senescent adult human dermal fibroblasts. The reduced production of H2S falls within the same time-frame that the hallmarks of replicative senescence appear including accumulation of SA–β-Gal, enhanced expression of p16, p21, and RRM2B while the expression of RRM2, hTERT, SIRT1, NAMPT, and NAD/NADH ratio all fall. Exogenous H2S increases the expression of hTERT, NAMPT, SIRT1 and NAD/NADH ratio in treated cells. Moreover, H2S safeguards the expression of hTERT in a NAMPT and SIRT1 dependent manner and delays the onset of replicative senescence as evidenced by reduced accumulation of age associated SA–β-Gal and cessation of proliferation. Postponement of loss of cell proliferative capacity without risk of mutagenesis shows implications for use of H2S in delaying the adverse effects of senescence in organisms.
Highlights
There are several lines of evidence that the gasotransmitter, hydrogen sulfide (H2S) has cytoprotective and life extension properties
Replicative senescence leads to reduced production of hydrogen sulfide We assessed the production of H2S in young and replicative senescent (PD: 18.8) Adult human dermal fibroblasts (aHDF) cells
We examined whether the effect of H2S on hTERT is NAMPT and SIRT1 dependent
Summary
There are several lines of evidence that the gasotransmitter, H2S has cytoprotective and life extension properties. It was shown that the generation of reactive oxygen species is increased in knockouts of mpst-1, a major enzyme that drives the production of hydrogen sulfide in C. elegans and this deficit is overcome by the administration of GY4137 that exposes the short-lived mutants to hydrogen sulfide [1]. This treatment extends the lifespan of normal animals and delays the onset of detrimental impact of senescence as assessed by pharyngeal contraction and defecation [1]. SIRT1 reduces stress induced apoptotic cell loss by deacetylation of PLOS ONE | DOI:10.1371/journal.pone.0164710 October 12, 2016
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