Kim Byunggik, Lee Dong I, Basisty Nathan, Dai Dao-Fu
Division of Cardiology, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
Cells. 2025 Aug 18;14(16):1278. doi: 10.3390/cells14161278.
Aging, a state of progressive decline in physiological function, is an important risk factor for chronic diseases, ranging from cancer and musculoskeletal frailty to cardiovascular and neurodegenerative diseases. Understanding its cellular basis is critical for developing interventions to extend human health span. This review highlights the crucial role of in vitro models, discussing foundational discoveries like the Hayflick limit and the senescence-associated secretory phenotype (SASP), the utility of immortalized cell lines, and transformative human induced pluripotent stem cells (iPSCs) for aging and disease modeling and rejuvenation studies. We also examine methods to induce senescence and discuss the distinction between chronological time and biological clock, with examples of applying cells from progeroid syndromes and mitochondrial diseases to recapitulate some signaling mechanisms in aging. Although no in vitro model can perfectly recapitulate organismal aging, well-chosen models are invaluable for addressing specific mechanistic questions. We focus on experimental strategies to manipulate cellular aging: from "steering" cells toward resilience to "reversing" age-related phenotypes via senolytics, partial epigenetic reprogramming, and targeted modulation of proteostasis and mitochondrial health. This review ultimately underscores the value of in vitro systems for discovery and therapeutic testing while acknowledging the challenge of translating insights from cell studies into effective, organism-wide strategies to promote healthy aging.
衰老,作为一种生理功能逐渐衰退的状态,是慢性疾病的重要风险因素,涵盖从癌症、肌肉骨骼衰弱到心血管和神经退行性疾病等多种疾病。了解其细胞基础对于开发延长人类健康寿命的干预措施至关重要。本综述强调了体外模型的关键作用,讨论了诸如海弗利克极限和衰老相关分泌表型(SASP)等基础发现、永生化细胞系的效用,以及用于衰老和疾病建模及年轻化研究的转化型人类诱导多能干细胞(iPSC)。我们还研究了诱导衰老的方法,并讨论了时间年龄与生物钟之间的区别,举例说明了如何应用早衰综合征和线粒体疾病患者的细胞来重现衰老过程中的一些信号传导机制。尽管没有任何体外模型能够完美重现机体衰老,但精心选择的模型对于解决特定的机制问题具有极高价值。我们重点关注操纵细胞衰老的实验策略:从引导细胞走向恢复力,到通过衰老细胞溶解剂、部分表观遗传重编程以及对蛋白质稳态和线粒体健康的靶向调节来“逆转”与年龄相关的表型。本综述最终强调了体外系统在发现和治疗测试方面的价值,同时也认识到将细胞研究中的见解转化为有效的、全机体范围的促进健康衰老策略所面临的挑战。
Cells. 2025-8-18
Cell Commun Signal. 2025-6-19
Biomolecules. 2025-6-13
Biogerontology. 2025-7-9
Adv Pharmacol. 2025
Biochim Biophys Acta Mol Basis Dis. 2025-2
NeuroSci. 2024-10-12
Nat Rev Mol Cell Biol. 2024-12
Front Aging. 2024-3-21