长寿
健康衰老
计算机科学
风险分析(工程)
心理干预
认知科学
成功老龄化
心理学
有机体
忠诚
机制(生物学)
认知心理学
人口老龄化
生命历程法
钥匙(锁)
结果(博弈论)
神经科学
细胞衰老
概念框架
生物年龄
老年学
系统生物学
标识
DOI:10.1073/pnas.2605454123
摘要
Biological aging is complex and resists any single mechanistic narrative. This article develops a conceptual framework for aging biology through a series of brief statements on central topics in the field, with the goal of discussing aging simply, directly and accessibly. The organizing principle is that aging is a default outcome of living: because biological processes are inherently imperfect, deleterious changes (the deleteriome) accumulate over time and progressively erode functional reserve. The deleteriome provides a unifying framework for molecular damage, regulatory drift, maladaptive remodeling, and system-level failure, without reducing aging to individual genes, pathways, compartments, hallmarks, or pathologies. Evolution does not program aging; it shapes maintenance and renewal systems that oppose this trajectory with limited fidelity and unavoidable trade-offs. Aging begins during development, following an early embryonic phase of rejuvenation. Modern biomarkers make biological age imperfectly but increasingly measurable. Biological age is heterogeneous across cells, organs, and systems, modifiable by interventions and environment, and in some contexts partially reversible or resettable, although aging itself is irreversible. This model links first principles of aging to measurement, intervention, and longer-term strategies, with the goal of clarifying how substantial longevity gains might be achieved, both within and beyond existing species-level constraints.
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