Is “cellular senescence” a misnomer?

Abstract

One of the most striking findings in biogerontology in the 2010s was the demonstration that elimination of senescent cells delays many late-life diseases and extends lifespan in mice. This implied that accumulation of senescent cells promotes late-life diseases, particularly through action of senescent cell secretions (the senescence-associated secretory phenotype, or SASP). But what exactly is a senescent cell? Subsequent to the initial characterization of cellular senescence, it became clear that, prior to aging, this phenomenon is in fact adaptive. It supports tissue remodeling functions in a variety of contexts, including embryogenesis, parturition, and acute inflammatory processes that restore normal tissue architecture and function, such as wound healing, tissue repair after infection, and amphibian limb regeneration. In these contexts, such cells are normal and healthy and not in any way senescent in the true sense of the word, as originally meant by Hayflick. Thus, it is misleading to refer to them as “senescent.” Similarly, the common assertion that senescent cells accumulate with age due to stress and DNA damage is no longer safe, particularly given their role in inflammation—a process that becomes persistent in later life. We therefore suggest that it would be useful to update some terminology, to bring it into line with contemporary understanding, and to avoid future confusion. To open a discussion of this issue, we propose replacing the term cellular senescence with remodeling activation, and SASP with RASP (remodeling-associated secretory phenotype).

Yearning for machine learning: applications for the classification and characterisation of senescence

“…The term was then used by Hayflick and Moorhead in 1961, to describe the specific cellular property of finite proliferative potential (the Hayflick limit) (Hayflick and Moorhead 1961). Subsequently, a variety of additional terms have emerged including, but not limited to, cell senescence, cellular senescence, replicative senescence, epithelial senescence, immunosenescence and cellular aging (Gems and Kern 2022). This varied nomenclature is indicative of the growing number of biological contexts in which senescent cells have been demonstrated to occur and contribute.…”

Cellular senescence: when growth stimulation meets cell cycle arrest

“…This is an age-independent cellular senescence that may occur at any age. This is also called non-adaptive cell senescence [20].…”

“…Geroconversion can be called gerogenic differentiation. This topic links the organismal/body growth program, hypertrophic differentiation, and geroconversion as a quasi-program of cellular growth and developmentally programmed cellular senescence [20].…”

“…While cell senescence is a quasi-programmed in aging, it may be programed in development [20,[41][42][43][44][45]. During mammalian embryonic development, senescent cells are cleared by macrophages, resulting in tissue remodeling [41].…”

“…Cell senescence is associated with constitutive, proliferative-like activity of nutrientsensing and growth-promoting pathways such as mTOR in non-proliferative (arrested) cells. David Gems and Carina Kern suggested replacing the term cellular senescence with remodeling activation, and SASP with RASP [20]. The key word is activation.…”