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Abstract
The molecular determinants of lifespan can be examined in animal models with the long-term objective of applying what is learned to the development of strategies to enhance longevity in humans. Here, we comment on a recent publication examining the molecular mechanisms that determine lifespan in worms, Caenorhabditis elegans (C. elegans), where it was shown that inhibiting protein synthesis increased levels of the transcription factor, ATF4. Gene expression analyses showed that ATF4 increased the expression of genes responsible for the formation of the gas, hydrogen sulfide (H2S). Further examination showed that H2S increased longevity in C. elegans by modifying proteins in ways that stabilize their structures and enhance their functions. H2S has been shown to improve cardiovascular performance in mouse models of heart disease, and clinical trials are underway to test the effects of H2S on cardiovascular health in humans. These findings support the concept that nutrient deprivation, which slows protein synthesis and leads to ATF4-mediated H2S production, may extend lifespan by improving the function of the cardiovascular system and other systems that influence longevity in humans.
Keywords
ATF4
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mTORC1
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protein synthesis
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hydrogen sulfide
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longevity
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Erik A. Blackwood, Christopher C. Glembotski.
Hydrogen sulfide: the gas that fuels longevity.
The Journal of Cardiovascular Aging, 2022, 2(3): 26 DOI:10.20517/jca.2022.16
| [1] |
Liberale L,Camici GG.Ageing and longevity genes in cardiovascular diseases.Basic Clin Pharmacol Toxicol2020;127:120-31
|
| [2] |
Sokolov SS.Manipulating cellular energetics to slow aging of tissues and organs.Biochemistry (Mosc)2020;85:651-9
|
| [3] |
Liu GY.mTOR at the nexus of nutrition, growth, ageing and disease.Nat Rev Mol Cell Biol2020;21:183-203 PMCID:PMC7102936
|
| [4] |
Statzer C,Venz R.ATF-4 and hydrogen sulfide signalling mediate longevity in response to inhibition of translation or mTORC1.Nat Commun2022;13:967 PMCID:PMC8857226
|
| [5] |
Longchamp A,Arduini A.Amino acid restriction triggers angiogenesis via GCN2/ATF4 regulation of VEGF and H2S production.Cell2018;173:117-129.e14 PMCID:PMC5901681
|
| [6] |
LaPenna KB,Doiron JE.Hydrogen sulfide as a potential therapy for heart failure-past, present, and future.Antioxidants (Basel)2021;10:485 PMCID:PMC8003444
|
| [7] |
Testai L,Martelli A,Calderone V.Role of hydrogen sulfide in cardiovascular ageing.Pharmacol Res2020;160:105125
|
| [8] |
Bithi N,Henderson YO.Dietary restriction transforms the mammalian protein persulfidome in a tissue-specific and cystathionine γ-lyase-dependent manner.Nat Commun2021;12:1745 PMCID:PMC7979915
|
| [9] |
Vanhoutte D,Vo A.Thbs1 induces lethal cardiac atrophy through PERK-ATF4 regulated autophagy.Nat Commun2021;12:3928 PMCID:PMC8225674
|
| [10] |
Grandjean JMD.Small molecule strategies to harness the unfolded protein response: where do we go from here?.J Biol Chem2020;295:15692-711 PMCID:PMC7667976
|