Beyond Binary Senescence: Intermediate Cellular States, Tissue Distribution, and Therapeutic Implications in Ageing

Ageing is associated with changes in cellular senescence, which may be better understood as a continuum rather than a binary state.

• Previous studies have reported increases in senescence markers with age across various tissues and species.
• Definitions of intermediate and senescent states have varied across studies, complicating cross-study comparisons.
• Evidence from replicative senescence models and mouse ageing studies supports a redefinition of senescence as a continuum.
• Senescent populations, even when numerically rare, may have significant effects on tissue function.
• Intermediate-stage cells could represent a distinct, potentially reversible target for therapeutic interventions.

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