数据日期 2026-10-29 · 生成时间 2026-10-29 06:03
研究问题
The biology of aging and the epidemiology of cardiovascular disease share a common molecular pathway expressed through nutrient-sensing kinases, mitochondrial redox state, and chronic inflammation.
方法
GLP-1RA-induced weight loss is associated with 25–39% of total lost mass being lean tissue [10], as suggested by data published in several clinical trials, but the degree of lean-mass attrition and its possible long-term musculoskeletal and immunological consequences are not yet resolved by available data—another reason why we did not include GLP-1RA in this review.；Consequently, the mechanistic convergence described in this review should be interpreted as hypothesis-generating rather than as evidence of a causal, generalizable geroprotective effect.
核心结论
GLP-1RA-induced weight loss is associated with 25–39% of total lost mass being lean tissue [10], as suggested by data published in several clinical trials, but the degree of lean-mass attrition and its possible long-term musculoskeletal and immunological consequences are not yet resolved by available data—another reason why we did not include GLP-1RA in this review.；The consequent fall in insulin and rise in the glucagon–insulin ratio shifts hepatic metabolism towards fatty-acid β-oxidation and ketogenesis, producing circulating β-hydroxybutyrate (β-OHB) concentrations of approximately 0.3–0.5 mM, metabolically analogous to early fasting [22].；These findings are derived from in vitro and animal studies and await confirmation in human cardiac tissue [24]. β-OHB additionally inhibits NLRP3 inflammasome assembly via direct protein binding [25] and suppresses class I histone deacetylases… ‖ 结论：We interpret two points as important for safe clinical translation of this framework: (1) the SGLT2i–prolonged fasting combination carries a genuine risk of euglycemic DKA and should be managed with sick-day rules; and (2) metformin should not be deployed in highly exercise-trained individuals without explicit discussion of its potential to attenuate training-induced healthspan benefits.
局限
A further limitation concerns causal inference itself.
对本项目的价值
★★★★☆ 代谢轴既干预敏感性最高，也是老药新用供给最充足的来源。命中核心 mTOR/AMPK；设计 RCT、观察性。
全文来源
PMC JATS 全文（正文 39,545 字符，已过标题/DOI 逐字归属校验）
原文题录
- 英文标题：Metformin, SGLT2 Inhibitors, and Intermittent Fasting: Convergent Pathways to Healthspan Extension, Cardiovascular Longevity, and Cancer Prevention-A Narrative Review.
- 期刊与标识：Curr Issues Mol Biol · PMID 42939546 · DOI 10.3390/cimb48101008**
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