Ageing as a two-phase process: theoretical framework

Area of Science:

• Gerontology and Evolutionary Biology
• Molecular and Developmental Biology

Background:

• Human and model organism ageing is typically viewed as a continuous decline in biological function and increasing mortality.
• Existing definitions of ageing are challenged by the diverse ageing patterns observed across species.
• The concept of 'hallmarks of ageing' identifies common biological processes associated with ageing.

Purpose of the Study:

• To introduce and explore a novel framework for understanding ageing as a non-linear process.
• To challenge conventional definitions of ageing and its evolutionary trajectory.
• To highlight the significance of the 'Smurf' phenotype in identifying distinct ageing phases.

Main Methods:

• Review of existing literature on ageing, frailty, and molecular clocks.
• Analysis of the 'Smurf' phenotype in *Drosophila* and its validation in other model organisms (nematodes, zebrafish, mice).
• Development of a mathematical framework for longevity trends based on experimentally measurable parameters.

Main Results:

• The 'Smurf' phenotype, characterized by age-linked intestinal permeability, consistently predicts mortality across diverse species.
• This phenotype reveals that ageing is not a continuous decline but comprises two distinct, discernible phases.
• A new mathematical model quantifies longevity trends based on three key parameters.

Conclusions:

• The Smurf phenotype provides a powerful tool to distinguish between chronological and biological age, and to identify distinct ageing phases.
• This research proposes a paradigm shift in ageing research, moving from a linear to a two-phase model.
• The findings offer new perspectives on the evolution of ageing and potential interventions to modulate the ageing process.