Hydrogen Sulfide Is an Endogenous Regulator of Aging in <i>Caenorhabditis elegans</i>

Qabazard, Bedoor; Li, Ling; Gruber, Jan; Peh, Meng Teng; Ng, Li Fang; Kumar, Srinivasan Dinesh; Rose, Peter; Tan, Choon‐Hong; Dymock, Brian; Wei, Feng; Swain, Sarat Chandra; Halliwell, Barry; Stürzenbaum, Stephen R.; Moore, Philip K.

doi:10.1089/ars.2013.5448

Cited by 84 publications

(100 citation statements)

References 32 publications

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“…PCR‐based damage quantification was done as described elsewhere (Gruber et al, 2011; Melov et al, 1995; Qabazard et al, 2014). Briefly, following mtDNA extraction and purification, mtDNA damage was assessed using two independent qRT‐PCRs: short‐qRT‐PCR and extra‐long qRT‐PCR.…”

Section: Methodsmentioning

confidence: 99%

Clonal expansion of mitochondrial DNA deletions is a private mechanism of aging in long‐lived animals

Lakshmanan

Yee

et al. 2018

Aging Cell

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Disruption of mitochondrial metabolism and loss of mitochondrial DNA (mtDNA) integrity are widely considered as evolutionarily conserved (public) mechanisms of aging (López‐Otín et al., Cell, 153, 2013 and 1194). Human aging is associated with loss in skeletal muscle mass and function (Sarcopenia), contributing significantly to morbidity and mortality. Muscle aging is associated with loss of mtDNA integrity. In humans, clonally expanded mtDNA deletions colocalize with sites of fiber breakage and atrophy in skeletal muscle. mtDNA deletions may therefore play an important, possibly causal role in sarcopenia. The nematode Caenorhabditis elegans also exhibits age‐dependent decline in mitochondrial function and a form of sarcopenia. However, it is unclear if mtDNA deletions play a role in C. elegans aging. Here, we report identification of 266 novel mtDNA deletions in aging nematodes. Analysis of the mtDNA mutation spectrum and quantification of mutation burden indicates that (a) mtDNA deletions in nematode are extremely rare, (b) there is no significant age‐dependent increase in mtDNA deletions, and (c) there is little evidence for clonal expansion driving mtDNA deletion dynamics. Thus, mtDNA deletions are unlikely to drive the age‐dependent functional decline commonly observed in C. elegans. Computational modeling of mtDNA dynamics in C. elegans indicates that the lifespan of short‐lived animals such as C. elegans is likely too short to allow for significant clonal expansion of mtDNA deletions. Together, these findings suggest that clonal expansion of mtDNA deletions is likely a private mechanism of aging predominantly relevant in long‐lived animals such as humans and rhesus monkey and possibly in rodents.

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Section: Methodsmentioning

confidence: 99%

Clonal expansion of mitochondrial DNA deletions is a private mechanism of aging in long‐lived animals

Lakshmanan

Yee

et al. 2018

Aging Cell

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“…Confirmation of the H 2 S releasing properties of GYY4137 within biological settings has also been demonstrated. Release of H 2 S from GYY4137 has now being independently verified using a range of assay procedures including use of the fluorescent probe 2,6-dansyl azide and 5,5 0 -dithiobis(2-nitrobenzoic acid) (Qabazard et al, 2014) alongside more refined procedures such as the H 2 S selective polarographic electrode (Kolluru, Shen, Bir, & Kevil, 2013) and detection of H 2 S using fluorescent HPLC analysis of monobromobimane derivatives (Shen, Peter, Bir, Wang, & Kevil, 2012).…”

Section: The Development and Characterization Of Gyy4137mentioning

confidence: 99%

“…Recently, it has been hypothesized that H 2 S plays a fundamental role in the aging process (Zhang et al, 2013). Evidence that H 2 S plays a role in this process stems from a number of observations notably, that H 2 S can inhibit oxidative stress (Benetti et al, 2013;Whiteman et al, 2004), increase longevity in some model organisms (Miller & Roth, 2007) and promote the induction of genes associated with longevity (Lee, Kennedy, Tolonen, & Ruvkun, 2003;Qabazard et al, 2014). H 2 S also reduces cell senescence and promotes cellular cytoprotective systems (Predmore, Alendy, Ahmed, Leeuwenburgh, & Julian, 2010).…”

Section: Gyy4137 and Agingmentioning

confidence: 99%

“…The big question is how does H 2 S influence the aging process and can GYY4137 be utilized as an antiaging drug in the sense of reducing the incidence or severity of age-related diseases? Recent evidence has indicated that GYY4137 can indeed reduce the deleterious effects of the aging process at least in the model nematode worm Caenorhabditis elegans (Qabazard et al, 2013(Qabazard et al, , 2014. For example, GYY4137 treatment increased the expression of several age-related, stress response, and antioxidant genes.…”

Section: Gyy4137 and Agingmentioning

confidence: 99%

“…For example, GYY4137 treatment increased the expression of several age-related, stress response, and antioxidant genes. Moreover, GYY4137 increases lifespan in short-lived mev-1 mutants with elevated oxidative stress and protected wild-type C. elegans against paraquat induced poisoning which is believed to occur via the generation of an excess of superoxide anions (Qabazard et al, 2013(Qabazard et al, , 2014.…”

Section: Gyy4137 and Agingmentioning

confidence: 99%

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