洛克菲勒大学细胞生物学家曹君越透过分析小鼠不同生命阶段约两千一百万个细胞的基因表达数据，提出衰老并非随机的分子磨损，而是一个有序的、阶段性的程序化过程。他的研究团队从约五十只雌雄小鼠的十四种组织或器官中取样，建立了庞大的单细胞基因表达数据集，发现衰老过程中只有约四分之一的细胞亚型发生显著变化，其余则在整个生命周期中保持稳定，这表明衰老并非普遍影响所有细胞，而是针对特定易感细胞群体。（关键数字：21, 14, 50, 1,828）
曹君越的研究揭示了哺乳动物衰老的离散阶段：在小鼠三至六个月（相当于人类二十至三十岁）时，特定脂肪细胞、肌肉细胞及脑中未成熟细胞开始减少；六至十二个月（人类三四十岁）时，维持身体组织的关键细胞如腱细胞、血管周围细胞和肾上皮细胞大量耗竭；约十二个月后（人类四五十岁），衰老从细胞耗竭转向细胞扩增，免疫细胞大量增生；十六个月后（人类五十多岁以后），与衰老相关的特化免疫细胞失控扩张，可能导致心脏病、关节炎和癌症等炎症性疾病风险升高。（关键数字：20, 30, 40）
这项研究对抗衰老策略具有重要启示。曹君越的团队识别出二十八万个在特定细胞类型衰老过程中可重复开启或关闭的基因组区域，证明衰老受到上游分子信号——包括控制基因表达的蛋白质和细胞因子——的调控，而非随机损伤所致。他将此过程比喻为秋天的落叶：并非线性衰退，而是由信号触发的协调性变化。研究还表明，人体的再生能力在中年之前就已开始下降，因此抗衰老干预应尽早开始。（关键数字：280,000, 30）
Cell biologist Junyue Cao at Rockefeller University has challenged the prevailing view that aging results from random molecular wear and tear. By profiling gene expression in 21 million cells sampled from 14 tissues across roughly 50 mice at five life stages, his team discovered that aging proceeds through discrete, coordinated stages resembling embryonic development. Only about one-quarter of the 1,828 cell subtypes identified showed significant shifts during aging, while the rest remained stable, indicating that aging selectively targets specific vulnerable cell populations rather than universally degrading all cells.
Cao's data revealed a structured timeline of cellular remodeling in mice that likely parallels human aging. Early stages (equivalent to the human 20s and 30s) involve the loss of certain fat, muscle, and brain progenitor cells, followed by depletion of tissue-maintaining cells such as tenocytes, vascular support cells, and kidney epithelial cells during the equivalent of the human 30s and 40s. Around midlife, the pattern shifts from cell loss to cell expansion, dominated by immune cells and stress-altered cells in various organs. In later stages, specialized aging-associated immune cells proliferate uncontrollably, contributing to increased risks of inflammatory diseases including heart disease, arthritis, and cancer.
These findings carry profound implications for anti-aging interventions. Cao's team identified 280,000 genomic regions that are reproducibly activated or silenced during aging in specific cell types, pointing to an upstream molecular program rather than stochastic damage. Internal regulators—proteins controlling gene expression—and external signaling molecules called cytokines together orchestrate these cellular changes. Cao compares the process to autumn leaf fall: not gradual but triggered by signals that rapidly transform the system. Critically, his research shows that the body's regenerative capacity declines before middle age, suggesting that effective anti-aging strategies must begin early, potentially before age 30 in humans.