《生命科学》 2026, 38(6): 972-980

脂肪组织衰老：系统性衰老的早期感应器与关键驱动者

刘娟宏¹ , 刘 峰^1,2,3,*

¹中南大学湘雅二医院代谢内分泌科，内分泌与代谢性疾病国家临床医学中心，中南大学代谢综合征研 究中心，长沙 410011 ²芙蓉实验室，长沙 410013 ³湖南省心血管代谢医学重点实验室，长沙 410013

摘　要：

越来越多的研究显示，代谢功能衰退并非衰老过程中被动出现的结果，而更可能是决定衰老速度与个体差异的核心驱动力。本文整合多层证据，提出“代谢稳态失衡驱动衰老”框架：营养感知失调、NAD+与氧化还原紊乱、线粒体质量控制受损等代谢稳态被破坏，构成衰老的早期事件。其中，脂肪组织因最早、最敏感地响应营养、免疫与环境压力，通过代谢弹性下降、免疫-代谢重塑介导的纤维化及器官间通讯异常，将局部失衡扩散至肝、肌、血管和大脑，推动系统性衰老。基于此，我们重新审视热量限制、间歇性禁食、运动、mTOR-AMPK-Sirtuin调控、线粒体干预及肠促胰岛素类药物的代谢基础，并展望多组学代谢时钟及靶向脂肪组织的精准干预。综上，脂肪组织可能是系统性衰老的早期感知器与驱动器，为抗衰策略提供了新方向。

通讯作者：刘 峰 , Email:liuf001@csu.edu.cn

Adipose tissue: The early sensor and driver of systemic aging

LIU Juan-Hong¹ , LIU Feng^1,2,3,*

¹National Clinical Research Center for Metabolic Diseases, Metabolic Syndrome Research Center, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha 410011, China ²FuRong Laboratory, Changsha 410013, China ³Hunan Provincial Key Laboratory of Cardiovascular and Metabolic Medicine, Changsha 410013, China

Abstract:

Aging is increasingly recognized as a metabolically driven process rather than a passive consequence of cumulative molecular damage. Increasing evidence indicates that disturbances in metabolic homeostasis emerge early and play an active role in shaping the rate and heterogeneity of aging. These metabolic perturbations not only precede overt functional decline but also influence the vulnerability of multiple organs to age-associated diseases. Among metabolic organs, adipose tissue is particularly susceptible to early aging-associated remodeling, undergoing profound structural and functional changes characterized by mitochondrial dysfunction, immune activation, fibrotic remodeling, and dysregulated endocrine and extracellular vesicle signaling. Importantly, these local changes propagate systemically through endocrine, immune, neural, and vesicle-mediated communication, driving metabolic decline in the liver, muscle, vasculature, and brain. Accordingly, aging-associated adipose tissue dysfunction emerges as both an early sensor and an active driver of organismal aging, positioning adipose tissue at the center of metabolism-aging crosstalk. In this review, we propose a metabolism-driven aging model in which adipose tissue acts as an early sensor and amplifier of aging signals, highlighting adipose metabolic resilience as a strategic target to delay aging. We summarize the pathophysiological alterations that occur in aging adipose tissue, emphasizing coordinated changes across multiple dimensions. These include immune-metabolic remodeling marked by chronic low-grade inflammation and dysregulated IgG-Fc receptor signaling; mitochondrial stress and hypoxia characterized by mitochondrial dysfunction, mtDNA damage, and aberrant HIF signaling; and progressive metabolic inflexibility manifested as insulin resistance and loss of metabolic plasticity. Concurrently, impaired endocrine function and disrupted inter-organ crosstalk, driven in part by altered adipokine and vesicle secretion, further contribute to functional deterioration across organ systems. We also discuss how established and emerging interventions—including caloric restriction, timerestricted eating, physical activity, mitochondrial-targeted approaches, and incretin-based therapies—can be reconsidered from the perspective of adipose tissue function. We suggest that strategies aimed at preserving adipose tissue metabolic resilience and maintaining inter-organ communication may offer an effective means to delay systemic aging and promote healthy aging.

Communication Author：LIU Feng , Email:liuf001@csu.edu.cn