"Accumulating evidence reveals that senescent cells are not merely deleterious pathological byproducts; rather, a subset plays indispensable physiological roles in embryonic development, wound healing, and the maintenance of tissue homeostasis."
BUFFALO, NY — May 15, 2026 — A new review was published in Volume 18 of Aging-US on May 4, 2026, titled " Cellular senescence: from pathogenic mechanisms to precision anti-aging interventions ."
The study was led by first author Jian Deng and corresponding author Dong Yang from the Department of Targeting Therapy and Immunology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China. In this comprehensive review, the authors examine how cellular senescence contributes to aging and age-related disease across multiple organ systems, while also highlighting the emerging complexity and functional diversity of senescent cell populations. Traditionally, senescent cells have been viewed primarily as harmful byproducts of aging, characterized by irreversible cell-cycle arrest and chronic inflammatory signaling. However, growing evidence suggests that some senescent cells also play beneficial physiological roles in tissue repair, embryonic development, and maintenance of tissue homeostasis.
The review outlines how senescence develops in major tissues including the liver, lungs, kidneys, heart, adipose tissue, brain, and skin. Across these organs, aging-related cellular dysfunction is driven by a combination of oxidative stress, mitochondrial dysfunction, DNA damage, chronic inflammation, metabolic stress, telomere shortening, and environmental insults such as ultraviolet radiation and pollution. The authors describe how senescent cells accumulate in highly specialized cell populations—including hepatocytes, endothelial cells, fibroblasts, macrophages, astrocytes, and epithelial cells—where they can disrupt normal tissue architecture and promote chronic disease progression.
Importantly, the article emphasizes that senescent cells are highly heterogeneous and should not be treated as a uniform population. Depending on the tissue context and biological environment, senescent cells may exert either protective or harmful effects. For example, certain senescent cells may help limit fibrosis or support wound healing, whereas others drive chronic inflammation, metabolic dysfunction, tissue degeneration, and cancer progression. This growing recognition of functional heterogeneity has prompted a major shift in anti-aging research away from indiscriminate elimination of senescent cells toward more selective and precision-based therapeutic strategies.
"Based on these insights, this review summarizes the induction mechanisms of cellular senescence and the subsequent evolution of their functional phenotypes across diverse tissues."
The review further explores the rapidly evolving landscape of anti-aging interventions. First-generation senolytic therapies—including dasatinib, quercetin, and fisetin—were designed to eliminate senescent cells by targeting pro-survival signaling pathways. More recent approaches now include highly targeted immunotherapies such as CAR-T cells directed against senescence-associated surface markers, as well as "senomorphic" therapies that suppress the inflammatory senescence-associated secretory phenotype (SASP) without destroying the cells themselves.
A major focus of the paper is the concept of "precision geroprotection," which aims to identify and selectively eliminate maladaptive senescent cell populations while preserving beneficial senescent cells that remain important for tissue stability and regeneration. The authors discuss how emerging technologies such as single-cell omics, lineage tracing, and spatial profiling may help researchers better characterize senescent cell subtypes and define safer therapeutic targets.
The review also highlights several important translational challenges that currently limit clinical application of senescence-targeted therapies. These include the lack of highly specific senescence biomarkers, difficulties in targeted drug delivery, risks of off-target tissue injury, and incomplete understanding of how senescent cell populations evolve over time within different organs. The authors caution that broad elimination of senescent cells could potentially disrupt tissue repair, immune surveillance, vascular integrity, or structural stability in vulnerable organs such as the heart, lungs, and brain.
Overall, this review presents a nuanced and evolving view of cellular senescence in aging biology. Rather than treating all senescent cells as uniformly harmful, the authors propose a more individualized strategy centered on prevention, functional characterization, and precision intervention. As anti-aging research continues to advance, these approaches may help support healthier aging while minimizing the risks associated with indiscriminate senescent cell removal.
Paper DOI: https://doi.org/10.18632/aging.206375
