Hydrogen sulfide in longevity and pathologies: Inconsistency is malodorous

Area of Science:

• Biochemistry
• Gerontology
• Molecular Biology

Background:

• Hydrogen sulfide (H2S) is a vital gasotransmitter involved in physiological processes and aging.
• H2S homeostasis, maintained by methionine and cysteine metabolism, is crucial; disruptions link to pathologies.
• Exogenous H2S shows geroprotective effects in C. elegans, but its impact on longevity and aging in other models is debated.

Purpose of the Study:

• To review the multifaceted role of H2S in aging.
• To discuss the challenges in translating H2S's geroprotective potential into therapies.
• To explore the complexities of H2S dosage, delivery, and natural levels in relation to longevity.

Main Methods:

• Literature review and synthesis of existing research on H2S and aging.
• Analysis of studies on H2S effects on longevity, stress resistance, and age-related pathologies.
• Examination of H2S molecular targets, biological effects, and dose-response relationships.

Main Results:

• Controversial effects of H2S on longevity, stress resistance, and senescence-associated secretory phenotype (SASP) across different models.
• H2S's therapeutic potential is complicated by numerous molecular targets and pleiotropic effects.
• Challenges exist in targeted H2S delivery and accurately measuring endogenous H2S levels and their correlation with lifespan.

Conclusions:

• The geroprotective translation of H2S is hindered by its complex pharmacology and dose-dependent effects.
• Further research is needed to clarify H2S's precise role in aging and to overcome delivery and dosage challenges.
• Understanding H2S homeostasis is critical for developing effective anti-aging strategies.