"Thirty years ago, the identification of activated beta-galactosidase during senescence led to one of the first characterizations of senescent cell accumulation during biological aging."
BUFFALO, NY — June 5, 2026 — A new review was published in Volume 18 of Aging on May 15, 2026, titled " Blue period – features of senescence 30 years after beta-galactosidase ."
The review was led by first author Chisaka Kuehnemann and corresponding author Christopher D. Wiley from Tufts University .
Cellular senescence has emerged as one of the most important biological processes linked to aging and age-related disease. Senescent cells stop dividing in response to stress or damage, yet they remain metabolically active and release a variety of signaling molecules that can influence surrounding tissues. Over the past three decades, evidence has increasingly shown that the accumulation of these cells contributes to chronic inflammation, tissue dysfunction, and many degenerative conditions associated with aging.
In this review, the authors examine how the field has evolved since the landmark discovery of senescence-associated beta-galactosidase (SA-β-gal) in 1995. That finding provided one of the first practical methods for identifying senescent cells and helped establish that these cells accumulate in aging tissues. Since then, researchers have identified numerous additional characteristics of senescence and developed new approaches to study their role in health and disease.
The review highlights several major features now recognized as hallmarks of senescent cells. These include stable proliferative arrest, increased lysosomal activity, secretion of inflammatory and signaling molecules collectively known as the senescence-associated secretory phenotype (SASP), mitochondrial dysfunction, alterations in nuclear architecture, accumulation of metals and lipofuscin, and enhanced survival despite exposure to cellular stress.
The authors explain that while biomarkers such as p16, p21, and SA-β-gal remain widely used, no single marker is sufficient to definitively identify senescent cells. Many features associated with senescence can also occur in other biological contexts, making it necessary to evaluate multiple characteristics simultaneously.
The review also discusses growing evidence that senescent cells communicate extensively with their environment through cytokines, extracellular vesicles, growth factors, and lipid mediators. These signals can influence inflammation, tissue remodeling, fibrosis, and aging-related dysfunction throughout the body.
Importantly, advances in senolytic therapies—treatments designed to selectively eliminate senescent cells—and interventions that suppress harmful SASP signaling have strengthened the view that senescence is not merely a marker of aging but an active contributor to disease processes.
"Because no single feature or marker of senescent cells is exclusive to the senescent state, it is recommended that multiple markers be used together for assessment of senescence."
The authors note that senescent cells are remarkably diverse, creating challenges for researchers trying to identify and target them while also opening new opportunities for therapeutic development. Modern technologies, including single-cell sequencing, multi-omics approaches, advanced imaging techniques, and computational analyses, are helping scientists better understand how senescence varies across tissues and disease states.
Taken together, the review offers a comprehensive look at how the understanding of cellular senescence has evolved since the discovery of SA-β-gal and highlights the challenges that remain as researchers work toward therapies that target aging-related disease. Thirty years after the landmark discovery of senescence-associated beta-galactosidase, the field continues to expand, providing new insights into the biological mechanisms that drive aging and age-related disorders.
Paper DOI: https://doi.org/10.18632/aging.206380
