超越900天规则:恢复健康寿命是老年科学的首要目标

IF 12.4 1区 医学 Q1 CELL BIOLOGY
Stef F. Verlinden
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引用次数: 0

摘要

最近在小鼠衰老研究中提出的“900天规则”——要求超长寿命对照组延长寿命——旨在确定调节内在衰老的干预措施。虽然这一标准提高了科学的严谨性,但它可能会降低大多数生物体(包括人类)实际衰老的相关性。实际上,衰老是在代谢和免疫压力的条件下展开的,而不是在无菌的、基因一致的环境中。大多数人在死前很久就经历了慢性炎症、代谢漂移和功能衰退。只优先考虑原始模型可能会忽视明显衰老的特征:虚弱、认知丧失、免疫侵蚀。这一观点提出了一种双轨策略:在理想模型中进行严格的寿命测试,应该辅以在现实世界的衰老模型中进行表型驱动的研究——比如在学术环境中常规饲养的小鼠——这反映了典型的衰老轨迹。像GlyNAC、NLRP3抑制和CaAKG这样的干预措施在现实世界的衰老模型中展示了广泛的功能益处——这些效果可能被视为“噪音”,但可能最有翻译意义。在CaAKG的情况下,即使寿命增长不大,虚弱程度也会大幅降低,这凸显了健康寿命与寿命的脱钩。通过拥抱内在衰老和外在衰老,老年科学可以更好地瞄准最重要的目标:提高大多数人的健康寿命,而不仅仅是少数人的寿命。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Beyond the 900-day rule: Reclaiming healthspan as geroscience’s primary goal
The recently proposed “900-day rule” in mouse aging studies—requiring lifespan extension over ultra-long-lived controls—aims to identify interventions that modulate intrinsic aging. While this standard raises scientific rigor, it may reduce relevance to how most organisms, including humans, actually age. In reality, aging unfolds under metabolically and immunologically stressful conditions—not in sterile, genetically uniform environments. Most people experience chronic inflammation, metabolic drift, and functional decline long before death. Prioritizing only pristine models risks overlooking the hallmarks of manifest aging: frailty, cognitive loss, immune erosion. This Viewpoint argues for a dual-track strategy: rigorous lifespan testing in ideal models should be complemented by phenotype-driven studies in real-world aging models—such as conventionally housed mice in academic settings—that reflect typical aging trajectories. Interventions like GlyNAC, NLRP3 inhibition, and CaAKG demonstrate broad functional benefits in real-world aging models—effects that may be dismissed as “noise” but are likely the most translationally meaningful. In the case of CaAKG, substantial reductions in frailty occurred even when lifespan gains were modest—highlighting the decoupling of healthspan from longevity. By embracing both intrinsic and manifest aging, geroscience can better target what matters most: improving healthspan for the many—not just lifespan for the few.
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来源期刊
Ageing Research Reviews
Ageing Research Reviews 医学-老年医学
CiteScore
19.80
自引率
2.30%
发文量
216
审稿时长
55 days
期刊介绍: With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends. ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research. The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.
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