Human pluripotent stem cells (hPSCs) have arisen as a source of cells for biomedical research due to their developmental potential. Stem cells possess the promise of providing clinicians with novel treatments for disease as well as allowing researchers to generate human-specific cellular metabolism models. Aging is a natural process of living organisms, yet aging in human heart cells is difficult to study due to the ethical considerations regarding human experimentation as well as a current lack of alternative experimental models. hPSC-derived cardiomyocytes (CMs) bear a resemblance to human cardiac cells and thus hPSC-derived CMs are considered to be a viable alternative model to study human heart cell aging. In this study, we used hPSC-derived CMs as an in vitro aging model. We generated cardiomyocytes from hPSCs and demonstrated the process of aging in both human embryonic stem cell (hESC)-and induced pluripotent stem cell (hiPSC)-derived CMs. Aging in hESC-derived CMs correlated with reduced membrane potential in mitochondria, the accumulation of lipofuscin, a slower beating pattern, and the downregulation of human telomerase RNA (hTR) and cell cycle regulating genes. Interestingly, the expression of hTR in hiPSC-derived CMs was not significantly downregulated, unlike in hESC-derived CMs. In order to delay aging, vitamin C was added to the cultured CMs. When cells were treated with 100 μM of vitamin C for 48 h, anti-aging effects, specifically on the expression of telomere-related genes and their functionality in aging cells, were observed. Taken together, these results suggest that hPSC-derived CMs can be used as a unique human cardiomyocyte aging model in vitro and that vitamin C shows anti-aging effects in this model.

Purpose: To investigate the effects of hydrogen sulfide (H2S) on the senescence and oxidative stress of cultured human trabecular meshwork cells (HTMCs). Methods: After inducing oxidative stress with 200 μM hydrogen peroxide (H2O2), primary cultured HTMCs were exposed to 0, 50, and 100 μM sodium hydrogen sulfide (NaHS) for 24 hours. Cell survival and senescence were measured using an MTT assay and SA-β-galactosidase staining, respectively. Generation of reactive oxygen species (ROS) and superoxide were measured using the dichlorofluorescein assay and modified cytochrome c assay. Production of nitric oxide (NO) and expression of eNOS mRNA were assessed using the Griess assay and reverse polymerase chain reaction. Results: Cell survival was not affected by 200 μM H2O2. Exposure to 50 and 100 μM NaHS significantly decreased cellular senescence, compared with the H2O2-exposed control. Exposure to 50 and 100 μM NaHS decreased the generation of ROS, and exposure to 100 μM NaHS decreased the generation of superoxide. Treatment with 100 μM NaHS increased the production of NO and expression of eNOS mRNA, respectively. Conclusions: NaHS decreased the cellular senescence associated with the decreased generation of free radicals. Thus, H2S could inhibit the senescence of HTMCs by reducing oxidative stress.