《生命科学》 2025, 37(4): 418-425

细胞衰老异质性的前沿研究技术进展

杜文华¹ , 孙　宇^1,2,* , 付　强^1,2,3,*

¹滨州医学院药学院衰老医学研究所，烟台 264003 ²上海交通大学抗衰老创新 中心，上海 200031 ³山东思乐基医药科技有限公司，烟台 264003

摘　要：

衰老细胞与机体衰老和病理状况高度相关，可以通过选择性靶向清除衰老细胞达到延缓衰老进程的目的。当衰老细胞在体内不能得到有效清除时，会引发一系列衰老相关的疾病，这将导致晚年发病率和死亡率增加。这激发了人们对寻找敏感而特异的衰老标志物的浓厚兴趣，但衰老相关表型的高度异质和动态性使之成为一项艰巨的挑战。近年来，除了广泛使用p16INK4a 作为衰老标志物之外，得益于高通量技术以及人工智能的发展，研究者发现了许多新的衰老标志物，这使人们能够在各个维度水平上分析衰老细胞。为揭示细胞、组织甚至物种之间衰老的异质性，本文提出迫切需要研究衰老异质性的潜在机制，并讨论如何通过应用先进技术、公开的测序数据以及人工智能来实现这一目标。

通讯作者：孙　宇 , Email:sunyu@sibs.ac.cn 付　强 , Email:qiangfu11@fudan.edu.cn

Advances in cutting-edge research techniques for cellular senescence heterogeneity

DU Wen-Hua¹ , SUN Yu^1,2,* , FU Qiang^1,2,3,*

¹Department of Aging Medicine, School of Pharmacy, Binzhou Medical University, Yantai 264003, China ²Anti-aging Innovation Center, Shanghai Jiaotong University, Shanghai 200031, China ³Shandong Cellogene Pharmaceutical Technology Co., Ltd., Yantai 264003, China

Abstract:

Senescent cells are closely associated with the aging process and pathological conditions of the body. Selectively targeting and eliminating senescent cells can delay the aging process. However, when senescent cells are not effectively cleared from the body, a series of age-related diseases will be triggered, leading to increased morbidity and mortality in later life. This has stimulated intense interest in the search for sensitive and specific markers of aging. Yet, the highly heterogeneous and  dynamic nature of aging-related phenotypes poses a significant challenge. In recent years, in addition to the widespread use of p16INK4a as a senescence marker, the development of high-throughput technologies and artificial intelligence has enabled the discovery of many new senescence markers. These advancements allow us to analyze senescent cells at various dimensional levels. To reveal the heterogeneity of aging among cells, tissues, and even species, we propose the urgent need to investigate the underlying mechanisms of aging heterogeneity. We discuss how to achieve this goal through the application of advanced technologies, publicly available sequencing data, and artificial  intelligence-based insights.

Communication Author：SUN Yu , Email:sunyu@sibs.ac.cn FU Qiang , Email:qiangfu11@fudan.edu.cn