Abstract
Aims. The study aimed to examine whether hydrogen sulfide (H2S) generation changed in the kidney of the ageing mouse and its relationship with impaired kidney function. Results. H2S levels in the plasma, urine, and kidney decreased significantly in ageing mice. The expression of two known H2S-producing enzymes in kidney, cystathionine γ-lyase (CSE) and cystathionine-β-synthase (CBS), decreased significantly during ageing. Chronic H2S donor (NaHS, 50 μmol/kg/day, 10 weeks) treatment could alleviate oxidative stress levels and renal tubular interstitial collagen deposition. These protective effects may relate to transcription factor Nrf2 activation and antioxidant proteins such as HO-1, SIRT1, SOD1, and SOD2 expression upregulation in the ageing kidney after NaHS treatment. Furthermore, the expression of H2S-producing enzymes changed with exogenous H2S administration and contributed to elevated H2S levels in the ageing kidney. Conclusions. Endogenous hydrogen sulfide production in the ageing kidney is insufficient. Exogenous H2S can partially rescue ageing-related kidney dysfunction by reducing oxidative stress, decreasing collagen deposition, and enhancing Nrf2 nuclear translocation. Recovery of endogenous hydrogen sulfide production may also contribute to the beneficial effects of NaHS treatment.
Highlights
Population ageing is a global phenomenon and exerts heavy demands on the healthcare system and society
Food and water intake were decreased whereas the urine volume increased in old control mice
Our work reveals two important findings: (1) lower plasma, urine, and kidney H2S levels and reduction of kidney cystathionine γ-lyase (CSE) and CBS expression and activity are accompanied with ageing; (2) exogenous administration of H2S donor NaHS mitigates ageing-related kidney dysfunction, and the protective effect of NaHS may at least partially relate to improved endogenous H2S production and its antioxidative nature
Summary
Population ageing is a global phenomenon and exerts heavy demands on the healthcare system and society. The aged population, 65 years or older, will reach 1 billion people, accounting for 13% of the total worldwide population in 2030 [1]. Ageing is a natural process accompanied by gradual declining in physiological functions. Impaired renal function in ageing people is of great clinical relevance and usually associates with cardiovascular diseases and even mortality. The characteristics of the ageing kidney include nephrosclerosis, nephron hypertrophy, cortical volume reduction, and cyst formation [2]. The high frequency of underlying diseases among ageing people, such as concurrent diabetes, complicates the treatment of nephropathy. Understanding the process of kidney ageing might help to improve the quality of life of the ageing population and to provide precise treatment for senile nephropathy
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