参考文献

衰老生物学基础

1. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: An expanding universe. Cell, 2023. doi:10.1016/j.cell.2022.11.001
2. The Hallmarks of Aging: From Molecular Mechanisms to Clinical Translation. PubMed Central, PMC13607713. 全文 — 对十二个标志逐一做因果证据评估，明确指出临床转化的限制。

热量限制

3. Belsky DW, Ryan CP, et al. Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial. Nature Aging, 2023. PMC10148951 — n=220，2 年，25% 热量限制；DunedinPACE 减缓约 2%–3%，PhenoAge 与 GrimAge 无显著变化。
4. CALERIE 试验设计与结果摘要：PMC10737863

运动与心肺适能

5. Mandsager K, Harb S, Cremer P, Phelan D, Nissen SE, Jaber W. Association of Cardiorespiratory Fitness With Long-term Mortality Among Adults Undergoing Exercise Treadmill Testing. JAMA Network Open, 2018. 全文 — n=122,007，中位随访 8.4 年，13,637 例死亡；最低适能 vs 精英适能 HR 5.04（95% CI 4.10–6.20）。
6. Kodama S, et al. Cardiorespiratory Fitness as a Quantitative Predictor of All-Cause Mortality and Cardiovascular Events in Healthy Men and Women: A Meta-analysis. JAMA, 2009. 全文 — 33 项研究、102,980 人；每 1 MET，全因死亡风险降低约 13%。
7. Paluch AE, et al. Daily steps and all-cause mortality: a meta-analysis of 15 international cohorts. The Lancet Public Health, 2022 — n=47,471。
8. Saint-Maurice PF, et al. Association of Daily Step Count and Step Intensity With Mortality Among US Adults. JAMA, 2020 — n=4,840，10 年随访。
9. Helgerud J, et al. Aerobic high-intensity intervals improve VO2max more than moderate training. Medicine & Science in Sports & Exercise, 2007.
10. Ross R, et al. Importance of Assessing Cardiorespiratory Fitness in Clinical Practice: A Case for Fitness as a Clinical Vital Sign. Circulation（AHA 科学声明）, 2016.

蛋白质与肌肉

11. Bauer J, et al. Evidence-Based Recommendations for Optimal Dietary Protein Intake in Older People: A Position Paper From the PROT-AGE Study Group. JAMDA, 2013. 全文
12. Morton RW, et al. A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength. British Journal of Sports Medicine, 2018 — 49 项 RCT、1,863 人。
13. Age-related muscle anabolic resistance: inevitable or preventable? Nutrition Reviews, 2023. 全文 — 含衰弱老年人抗阻训练效应量的汇总区间。

雷帕霉素

14. PEARL trial（Participatory Evaluation of Aging with Rapamycin for Longevity），Aging, 2025；注册号 NCT04488601 — 114 人、48 周、随机双盲安慰剂对照；主要终点（内脏脂肪）未达成。
15. Mannick JB, et al. mTOR inhibition improves immune function in the elderly. Science Translational Medicine, 2014 — everolimus，6 周，流感疫苗抗体反应提升约 20%。
16. Rapamycin in aging and disease（系统综述），The Lancet Healthy Longevity, 2024 — 结论为现有证据「不足以肯定，也不足以否定」其延寿效益。
17. NIA Interventions Testing Program (ITP) 的雷帕霉素结果汇总：9 月龄起给药，小鼠寿命延长 9%–14%，三个独立 site 重复。

衰老细胞清除（Senolytics）

18. Khosla S. Translating Senolytics From Mice to Humans. Innovation in Aging, 2025. doi:10.1093/geroni/igaf122.679 — 26 项注册 senolytic 研究、32 项非瑟酮研究，已发表临床试验仅 9 项，其中 2 项设对照。
19. Orr M. Clinical Trials of Senolytics in Alzheimer’s Disease Treatment and Prevention. Innovation in Aging, 2025. doi:10.1093/geroni/igaf122.1102 — SToMP（n=5）与 STAMINA（n=12）的设计与结果。
20. Hickson LJ, et al. Senolytics decrease senescent cells in humans. EBioMedicine, 2019 — 达沙替尼+槲皮素降低人体脂肪与皮肤中的衰老细胞负荷。
21. Justice JN, et al. Senolytics in idiopathic pulmonary fibrosis: results from a first-in-human, open-label, pilot study. EBioMedicine, 2019 — n=14。

NAD+ 前体

22. Direct comparison of NAD+ precursors in humans（NMN / NR / 烟酰胺交叉试验），Nature Metabolism, 2025. 全文 — 血 NAD+ 提升约 130%–150%。
23. Shoji M, et al. Nicotinamide riboside supplementation in Werner syndrome: a double-blind randomized crossover trial. Aging Cell, 2025 — n=9，1,000 mg/天，26 周交叉。综述汇总见 PMC12727671
24. Geroprotective Effects of Drugs Modulating Metabolic Pathways. 2025. PMC13565775 — 汇总 NMN/NR 的系统综述与 Meta 分析结论：标志物升高，肌肉功能指标无显著差异。

补剂

25. Singh P, et al. Taurine deficiency as a driver of aging. Science, 2023. 全文 — 小鼠与猴子数据为主。
26. Manson JE, et al. Marine n−3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer（VITAL）. New England Journal of Medicine, 2019 — 主要终点未达统计学显著。
27. Manson JE, et al. Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease（VITAL）. New England Journal of Medicine, 2019 — 主要终点未达统计学显著。

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