健康老龄化:老年科学的前景与风险
HEALTHY AGING: THE PROMISE, AND PERILS, OF GEROSCIENCE.
作者信息
High Kevin P
机构信息
Winston Salem, NC.
出版信息
Trans Am Clin Climatol Assoc. 2025;135:99-118.
Aging is a recent development in human history with nearly half of all median life expectancy gains occurring in the last two to three centuries. Aging is the strongest risk factor for medical conditions that predominately account for morbidity, mortality, and health care costs: cancer, heart disease, stroke, arthritis, and neurodegenerative disease. The geroscience hypothesis postulates that mechanisms of aging simultaneously drive multiple chronic illnesses and functional decline/disability, and intervening in the rate of aging can prevent multiple diseases. Geroscience now relies on 12 identified "hallmarks" or "pillars" of aging that involve alterations in genomic stability/repair, telomere length, epigenetics, proteostasis, macroautophagy, nutrient-sensing, mitochondrial function, cellular senescence, stem cell regeneration, intercellular communication, inflammation, and the microbiome. These pillars are mechanisms/pathways associated with aging, and evidence for causal associations is rapidly becoming more robust. Geroscience-based interventions may reduce illness burden-preserving function and independence-to a greater degree than addressing illnesses one by one. However, the pathway from promise to success is riddled with obstacles and potential pitfalls. Even success can have negative impacts on human populations and our planet that will require major shifts in society. Both the promises and perils of geroscience are likely to shape medical research and ethical debate for years to come.
衰老在人类历史上是一个近期才出现的现象,在过去两到三个世纪里,人类预期寿命中位数的增长近一半都发生在这期间。衰老是导致主要疾病、死亡和医疗费用的医学状况的最强风险因素,这些疾病包括癌症、心脏病、中风、关节炎和神经退行性疾病。老年科学假说认为,衰老机制同时驱动多种慢性疾病和功能衰退/残疾,干预衰老速度可以预防多种疾病。老年科学现在依赖于12个已确定的衰老“标志”或“支柱”,这些标志涉及基因组稳定性/修复、端粒长度、表观遗传学、蛋白质稳态、巨自噬、营养感应、线粒体功能、细胞衰老、干细胞再生、细胞间通讯、炎症和微生物群的改变。这些支柱是与衰老相关的机制/途径,因果关联的证据正迅速变得更加确凿。基于老年科学的干预措施可能比逐一治疗疾病更大程度地减轻疾病负担、保持功能和独立性。然而,从承诺到成功的道路充满了障碍和潜在的陷阱。即使取得成功,也可能对人类和我们的星球产生负面影响,这将需要社会发生重大转变。老年科学的前景和风险可能会在未来几年塑造医学研究和伦理辩论。
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NPJ Aging. 2024-8-17
J Gerontol A Biol Sci Med Sci. 2024-7-1
Mol Cell. 2024-1-4
Prog Cardiovasc Dis. 2023