《生命科学》 2026, 38(6): 1165-1179
长寿人群健康老龄发生机制研究进展
摘 要：
随着全球人口老龄化进程的加剧，衰老带来的系统性功能衰退，以及衰老相关疾病的高发对个人健康、社会公共卫生体系及经济可持续发展带来了前所未有的挑战。长寿人群作为成功延缓甚至规避重大增龄相关疾病的独特群体，为研究人类健康老龄提供了理想的自然模型，也是近年来国内外研究的焦点。本文从遗传基础、表达调控及环境生活方式等多个维度系统概述了当前针对长寿人群健康老龄机制的重要研究进展。在解析遗传蓝图对机体系统稳态维系方面，本文以FOXO3A、APOE等重要基因（突变）为例介绍了其如何通过重塑能量网络、优化脂质代谢谱系及构建免疫韧性来防御分子损伤，并探讨了遗传缓冲与环境筛选在长寿性别差异中的作用；其次，针对基因表达调控在机体健康老龄过程中的作用，本文概述了长寿个体如何通过维持年轻化的DNA甲基化景观和利用非编码RNA网络进行转录调控，以及增强蛋白质稳态与长寿的关联；而在剖析环境-机体互作这一外源性重塑力量时，本文重点关注并介绍了肠道微生态作为代谢与免疫共生引擎的关键角色，其与长寿间的因果关联，以及生活方式干预（如热量限制、运动与心理韧性）的保护效应。深入理解以上多维度的保护因子及其作用机制，不仅是解码人类长寿奥秘的关键，也为未来开发新型抗衰老策略提供了重要的理论依据。未来，以此为基础的转化研究有望推动从“长寿分子发现”向“长寿医学干预”的跨越，从而全面提升人类健康寿命，加速迈向高质量的健康老龄化社会。
通讯作者：孔庆鹏 , Email:kongqp@mail.kiz.ac.cn
Abstract:
With the acceleration of global population aging, the rising prevalence of age-related diseases presents unprecedented challenges to individual health, public health systems, and sustainable economic development. Long-lived individuals serve as ideal natural models for researching healthy aging, since they have successfully delayed or even avoided the onset of major age-related diseases. This unique longevity phenotype is not attributed to a single factor but reflects the cumulative protective contributions of multidimensional factors, including genetic endowment, epigenetic modifications, and environmental lifestyles. This article provides a comprehensive review of recent advances in understanding the mechanisms of healthy aging derived from longevity cohort studies. Firstly, we explore the foundational role of the genetic blueprint in maintaining systemic homeostasis. We discuss how important longevity loci, such as FOXO3A, APOE and IL-6, defend against molecular damage by reshaping energy networks, optimizing lipid metabolic profiles, and building immune resilience, while also exploring the roles of genetic buffering and environmental selection in sex differences in longevity. Then, we review current findings regarding gene expression regulation in healthy aging, noting that long-lived individuals exhibit younger DNA methylation landscapes and utilize non-coding RNA networks for transcriptional regulation, and mention the association between enhanced proteostasis and longevity. Finally, we discuss the exogenous influences of environment-organism interactions on the maintenance of healthy aging. We specifically focus on the role of the gut microbiota in supporting metabolism and immunity within longevity cohorts, as well as its causal
relationship with longevity, while also summarizing the combined benefits of lifestyle interventions, such as caloric restriction, physical exercise, and psychological resilience. Deeply understanding these multidimensional protective mechanisms is the key to decoding the mysteries of human longevity and provides a theoretical basis for developing novel anti-aging strategies. Future translational research based on these mechanisms is expected to drive the transition from ″longevity molecule discovery″ to ″longevity medical interventions″, ultimately extending human healthspan and facilitating a transition toward a high-quality healthy aging society.
Communication Author：KONG Qing-Peng , Email:kongqp@mail.kiz.ac.cn
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