Replicative Senescence in Human Fibroblast...
alc
19 Oct 2016
"Replicative Senescence in Human Fibroblasts Is Delayed by Hydrogen Sulfide in a NAMPT/SIRT1 Dependent Manner"
http://journals.plos...one.0164710.PDF
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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.
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