"The role of hydrogen sulfide in aging and age‐related pathologies"
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ABSTRACT
When humans grow older, they experience inevitable and progressive loss of physiological function, ultimately leading to death. Research on aging largely focuses on the identification of mechanisms involved in the aging process. Several proposed aging theories were recently combined as the ‘hallmarks of aging’. These hallmarks describe (patho‐)physiological processes that together, when disrupted, determine the aging phenotype. Sustaining evidence shows a potential role for hydrogen sulfide (H2S) in the regulation of aging. Nowadays, H2S is acknowledged as an endogenously produced signaling molecule with various (patho‐) physiological effects. H2S is involved in several diseases including pathologies related to aging. In this review, the known, assumed and hypothetical effects of hydrogen sulfide on the aging process will be discussed by reviewing its actions on the hallmarks of aging and on several age‐related pathologies.
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Hallmarks of aging In total, nine hallmarks of aging were proposed which together are thought to determine the aging phenotype.
The criteria for the hallmarks are that each hallmark should be manifested during normal aging and that its experimental intervention
should both accelerate or retard the normal aging process, depending on the intervention.
However, not all hallmarks currently meet up to all the criteria as amelioration of the aging process is not always successful.
The hallmarks are interconnected, making it difficult to determine the relative contribution of each hallmark to aging.
There is some degree of hierarchy between the hallmarks of aging and therefore they are divided into three categories: primary, antagonistic and integrative hallmarks.
Primary hallmarks, including genomic instability, telomere attrition, epigenetic alterations and loss of proteostasis, are considered to be the primary cause of damage at cellular level which progressively accumulates with time. In response, antagonistic hallmarks that are principally beneficial and mitigate damage may become deleterious themselves, progressively contributing to aging. Deregulated nutrient sensing, mitochondrial dysfunction and cellular senescence belong to this category. Finally, the integrative hallmarks arise when the tissue homeostatic mechanisms cannot compensate for the damage caused by the previous two categories. The integrative hallmarks, stem cell exhaustion and altered intercellular communication, are ultimately responsible for the age related functional declines.
All nine hallmarks of aging and the effects of H2S on each hallmark will be comprehensively discussed in this review.
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http://paperchase-ag...aC63j9JtJAS.pdf
