Cellular Models of Aging and Senescence

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 hum...

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Bibliographic Details
Published in:Cells (Basel, Switzerland) Vol. 14; no. 16; p. 1278
Main Authors: Kim, Byunggik, Lee, Dong I., Basisty, Nathan, Dai, Dao-Fu
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 18.08.2025
MDPI
Subjects:
Age
Aging
Animals
Atazanavir
Autophagy
Biological clocks
Cell culture
cellular aging
Cellular Senescence
Chronic diseases
Disease
DNA damage
Epigenetic inheritance
epigenetic reprogramming
Epigenetics
Fibroblasts
Humans
induced pluripotent stem cells (iPSCs)
Induced Pluripotent Stem Cells - metabolism
Kinases
Medical research
Medicine, Experimental
Metabolism
Mitochondria - metabolism
mitochondrial dysfunction
Models, Biological
Nervous system diseases
Neurodegenerative diseases
Phenotypes
Physiology
Pluripotency
Progeroid syndromes
Review
Risk factors
Senescence
Senescence-Associated Secretory Phenotype
senolytics
Stem cells
senescence
progeroid syndromes
cardiovascular aging
in vitro models
cellular aging
neurodegeneration
senolytics
epigenetic reprogramming
mitochondrial dysfunction
induced pluripotent stem cells (iPSCs)
ISSN:2073-4409, 2073-4409
Online Access:Get full text
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Summary: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.
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ISSN:2073-4409
2073-4409
DOI:10.3390/cells14161278