A new book review titled “Blue Era – Characteristics of Aging 30 Years After β-Galactosidase” has been published in Volume 18 of Aging, which will be released on May 15, 2026.
The peer review was led by first author Chisaka Kuehnemann and corresponding author Christopher D. Wiley of Tufts University.
Cellular senescence has emerged as one of the most important biological processes associated with aging and age-related diseases. Senescent cells stop dividing in response to stress or injury, but remain metabolically active and release a variety of signaling molecules that can affect surrounding tissues. Over the past three decades, there has been increasing evidence 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 breakthrough discovery of aging-associated β-galactosidase (SA-β-gal) in 1995. This discovery provided one of the first practical methods to identify senescent cells and helped establish that these cells accumulate in senescent tissues. Since then, researchers have identified many additional hallmarks of aging and developed new approaches to studying the role of aging in health and disease.
This review highlights some of the key features currently recognized as hallmarks of senescent cells. These include stable growth arrest, increased lysosomal activity, secretion of inflammatory and signaling molecules collectively referred to as the senescence-associated secretory phenotype (SASP), mitochondrial dysfunction, altered nuclear structure, metal and lipofuscin accumulation, and increased survival despite exposure to cellular stress.
The authors explain that although biomarkers such as p16, p21, and SA-β-gal are still widely used, no single marker is sufficient to definitively identify senescent cells. Many traits associated with aging can also occur in other biological contexts, so multiple traits need to be assessed simultaneously.
This review also discusses the growing evidence that senescent cells communicate extensively with the environment through cytokines, extracellular vesicles, growth factors, and lipid mediators. These signals can influence inflammation, tissue remodeling, fibrosis, and age-related dysfunction throughout the body.
Importantly, advances in senolytic therapy (treatments designed to selectively eliminate senescent cells) and interventions that inhibit harmful SASP signaling have strengthened the view that senescence is not just a marker of aging, but actively contributes to disease progression.
”As no single characteristic or marker of senescent cells is limited to the senescent state, it is recommended to use multiple markers together to assess aging.. ”
The authors note that senescent cells are incredibly diverse, creating challenges for researchers seeking to identify and target them, but also opening new opportunities for therapeutic development. Emerging technologies such as single-cell sequencing, multi-omics approaches, advanced imaging techniques, and computer analysis are helping scientists better understand how aging varies across tissues and disease states.
Taken together, this review provides a comprehensive look at how our understanding of cellular aging has evolved since the discovery of SA-β-gal, and highlights the challenges that remain as researchers work toward targeted therapies for aging-related diseases. Three decades after the groundbreaking discovery of aging-associated β-galactosidase, the field continues to expand, providing new insights into the biological mechanisms that drive aging and age-related disorders.
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Reference magazines:
https://doi.org/10.18632/aging.206380
