# Evolution of Senescence by Damage Accumulation That Accelerates With Age Throughout an Organism's Lifespan

## TL;DR

The paper proposes a new model for how aging evolves, focusing on genes affecting mortality throughout life and explaining puzzling biological phenomena.

## Contribution

A novel evolutionary model for senescence that incorporates lifelong mortality effects and explains unresolved biological patterns.

## Key findings

- A new evolutionary model shows how genes affecting mortality throughout life can drive senescence evolution.
- The model explains phenomena like Peto's paradox and negligible senescence previously unexplained by classic theories.
- Biological limitations on reducing internal damage can create feedback loops accelerating senescence evolution.

## Abstract

In recent years, senescence is increasingly understood as a process of damage accumulation that accelerates with age throughout an organism's lifespan. That understanding has rarely been introduced to senescence evolution theory. In classic models, including Mutation accumulation and Antagonistic pleiotropy, the intensity of selection over genes is determined by the timing of their effect on mortality. They conclude senescence evolution occurs because of weak selection on late‐acting genes. Here we explore, consistent with recent evidence, an alternative model: where genes affect mortality throughout an organism's lifespan, and the shape of this effect determines selection. We expanded Hamilton's classic model of senescence evolution using these notions. Our model takes into account evolutionary dynamics between external mortality risk, potential mortality risk from internal damage, reproduction start age, and reproduction rate. The analysis of the model suggests biological limitations on reducing the potential mortality risk from internal damage can lead to a positive feedback loop in senescence evolution where genes that slow senescence can increase selection for further senescence retardation. Our model sheds light on several phenomena, not fully explained by classic theory, including Peto's paradox, Strehler—Mildvan correlation, and negligible senescence.

Senescence evolution is usually explained by reduced selection on late acting genes. Here we develop a new model for senescence evolution that complements the classic theory by focusing on genes that affect mortality throughout lifespan. Our work sheds light on the dynamics of senescence evolution and helps to reconcile phenomena that presented challenges to the classical theory: negligible senescence, Peto's paradox, and Strehler—Mildvan correlation.