Beyond binary senescence: Intermediate cellular states, tissue distribution, and therapeutic implications in ageing

Area of Science:

• Gerontology
• Cell Biology
• Molecular Biology

Background:

• Cellular senescence is closely linked to ageing, with studies reporting increased senescence markers.
• Quantitative data across tissues and species on age-associated senescence changes are not systematically integrated.
• Inconsistent definitions of intermediate and senescent states hinder cross-study interpretation.

Purpose of the Study:

• To systematically integrate quantitative data on senescence-associated cell populations during ageing.
• To reframe cellular senescence as a continuum rather than a binary state.
• To explore therapeutic implications, including targeting intermediate-stage cells.

Main Methods:

• Synthesized evidence from replicative senescence models, human tissues, and mouse ageing studies.
• Compared definitions of intermediate-stage and senescent cells across studies.
• Summarized tissue distribution and relative abundance of these cells during ageing.

Main Results:

• Cellular senescence is presented as a continuum, challenging a simple binary classification.
• Tissue distribution and abundance of intermediate and senescent cells during ageing are summarized.
• Even rare senescent populations can disproportionately affect tissue function.

Conclusions:

• A quantitative and conceptual framework for interpreting cellular senescence in physiological ageing is provided.
• Intermediate-stage cells may represent a distinct, potentially reversible therapeutic window.
• This reframing aids in understanding the complex role of senescence in ageing and disease.