Replicative Senescence in Human Fibroblasts Is Delayed by Hydrogen Sulfide in a NAMPT/SIRT1 Dependent Manner.

Replicative Senescence in Human Fibroblasts Is Delayed by Hydrogen Sulfide in a NAMPT/SIRT1 Dependent Manner.
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DOI:
10.1371/journal.pone.0164710
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发表时间:
2016
期刊:
影响因子:
3.7
通讯作者:
Tabibzadeh S
Tabibzadeh S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Sanokawa-Akakura R;Akakura S;Tabibzadeh S

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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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