| dc.description.abstract | Aging involves the time-dependent deterioration of physiological functions, which can be attributed to various factors. Cellular senescence has been shown to be akin to aging, which involves alteration in redox homeostasis associated with an increase in reactive oxygen/nitrogen species (ROS/RNS), inflammatory gene expression, and senescence-associated beta-galactosidase activity, all markers of aging. Recently, it was proposed that gasotransmitters which include carbon monoxide (CO), hydrogen sulfide (H2S), and nitric oxide (NO), may also play an important role in regulating redox homeostasis during senescence.
Previously it has been reported that the levels of extracellular H2S decrease during aging. Over the years, the role of H2S has remained controversial, as it has been shown to induce DNA damage and protect against ischemia-reperfusion injury as well as suppress oxidative stress through the Nrf2-Keap1 signaling pathway. Interestingly, it has been shown to induce the expression of genes involved in longevity like SIRT1, Klotho [1], SKN-1/Nrf2 [2] etc.
To understand the role of H2S during aging, using various approaches, we probed H2S homeostasis in senescent and non-senescent cells. Using a combination of fluorescent reporter dyes for H2S and protein sulfhydration, we found that both the levels of free intracellular H2S and total protein sulfhydration are altered during senescence. Supplementation of H2S in cells using donors and depletion using targeted gene expression knockdown approaches for biosynthetic proteins altered the levels of free radicals, inflammatory molecules, ATP levels in the cells. Overall, we observed the levels of H2S alter the redox homeostasis during senescence, thereby affecting the inflammatory phenotype of aged cells. | en_US |
