Cellular senescence: six decades of discovery and reinvention.

Authors

Myrthe Klaver, Lotte Sophie Steeneken, Naomi Veeningen, Abdullah Altulea, Marco Demaria

Published in

The EMBO journal. Oct 02, 2026. Epub Oct 02, 2026.

Abstract

Cellular senescence has undergone a remarkable conceptual evolution since its discovery in 1961. Initially described by Hayflick and Moorhead as the finite proliferative lifespan of cultured human cells, senescence was first viewed as a consequence of cellular aging. The identification of telomere shortening, senescence biomarkers, and oncogene- and damage-induced senescence subsequently established its molecular basis and role as a tumor-suppressive stress response. The discovery of the senescence-associated secretory phenotype (SASP) further transformed the field by revealing that senescent cells actively communicate with and remodel their tissue environment. Genetic mouse models later demonstrated causal roles for senescent cells in tissue repair, aging, and age-related disease, while senotherapeutics established senescence as a therapeutic target. Here, we trace the major conceptual transitions that shaped the field, from replicative endpoint to stress-response program, regulator of tissue homeostasis, driver of chronic pathology, and clinically actionable process. We discuss the discoveries, controversies, and technological advances underlying these transitions and how emerging single-cell technologies, precision biomarkers, and targeted interventions are shaping the next era of senescence research.

PMID:
42827203
Bibliographic data and abstract were imported from PubMed on 03 Oct 2026.

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