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<p>Silent mating type information regulation 1 (SIRT1), a core molecule bridging energy metabolism and ageing modulation, relies on its nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase activity and pathway crosstalk to form a key regulatory network governing ageing. This review focuses on the central regulatory role of SIRT1 in cellular senescence, integrating its multidimensional mechanisms in deoxyribonucleic acid (DNA) damage response, inflammatory microenvironment modulation, autophagic function remodeling, and maintenance of energy metabolic homeostasis. Meanwhile, we summarized the intervention strategies targeting SIRT1 (e.g., small-molecule compounds and natural extracts) and the differences in their action targets, clarifying their translational potential in the prevention and treatment of ageing-related diseases. We further highlight emerging evidence on sex-specific differences, model specificity, and evolutionary conservation that shape SIRT1’s role in ageing. This review aims to provide a systematic perspective for in-depth understanding of the SIRT1-mediated ageing regulatory network, and offer a reference for basic anti-ageing research, optimization of precise intervention strategies, and screening of therapeutic targets for related diseases.</p>

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Molecular mechanisms of SIRT1 in regulating ageing and related intervention strategies

  • 期刊论文

  • 发表日期：

    2026年5月11日

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  • Yuting SUN,
  • Xueling Dai,
  • Yajun Lin,
  • Yaxuan Sun

摘要

Silent mating type information regulation 1 (SIRT1), a core molecule bridging energy metabolism and ageing modulation, relies on its nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase activity and pathway crosstalk to form a key regulatory network governing ageing. This review focuses on the central regulatory role of SIRT1 in cellular senescence, integrating its multidimensional mechanisms in deoxyribonucleic acid (DNA) damage response, inflammatory microenvironment modulation, autophagic function remodeling, and maintenance of energy metabolic homeostasis. Meanwhile, we summarized the intervention strategies targeting SIRT1 (e.g., small-molecule compounds and natural extracts) and the differences in their action targets, clarifying their translational potential in the prevention and treatment of ageing-related diseases. We further highlight emerging evidence on sex-specific differences, model specificity, and evolutionary conservation that shape SIRT1’s role in ageing. This review aims to provide a systematic perspective for in-depth understanding of the SIRT1-mediated ageing regulatory network, and offer a reference for basic anti-ageing research, optimization of precise intervention strategies, and screening of therapeutic targets for related diseases.