# Machine learning predicts lifespan and suggests underlying causes of death in aging C. elegans

## TL;DR

Machine learning models predict lifespan in C. elegans by analyzing age-related pathology patterns, revealing key organs and sex differences linked to aging.

## Contribution

A data-driven ML approach identifies how age-related pathology mediates genetic and environmental effects on lifespan in C. elegans.

## Key findings

- ML models predict lifespan variation with 79% accuracy based on mid-life pathology levels.
- Pharynx and intestine pathology are strongest predictors of lifespan in aging C. elegans.
- Sex differences in age-related pathology suggest reproductive aging is specific to hermaphrodites.

## Abstract

Aging leads to age-related pathology that causes death, and genes affect lifespan by determining such pathology. Here we investigate how age-related pathology mediates the effect of genetic and environmental interventions on lifespan in C. elegans by means of a data-driven approach employing machine learning (ML). To this end, extensive data on how diverse determinants of lifespan (sex, nutrition, genotype, mean lifespan range: 7.5 to 40 days) affect patterns of age-related pathology was gathered. This revealed that different life-extending treatments result in distinct patterns of suppression of senescent pathology. By analysing the differential effects on mid-life pathology levels and lifespan, the ML models developed were able to predict lifespan variation, explaining 79% of the variance. Levels of pathology in the pharynx and intestine proved to be the strongest predictors of lifespan. This suggests that elderly C. elegans die predominantly from late-life disease affecting these organs. In addition, we noted profound sex differences in age-related pathology: the striking age-related pathologies in hermaphrodites affecting organs linked to reproduction are absent from males, suggesting that reproductive death may be hermaphrodite limited.

Data-driven machine learning sheds light on how genes, environment and sexual dimorphism shapes aging in the model organism C. elegans.