In-silico evaluation of aging-related interventions using omics data and predictive modeling.

Abstract

A major challenge in aging research is identifying interventions that can improve lifespan and health and minimize toxicity. Clinical studies cannot usually consider decades-long follow-up periods, and therefore, in-silico evaluations using omics-based surrogate biomarkers are emerging as key tools. However, many current approaches train predictive models on observational data, rather than on intervention data, which can lead to biased conclusions. Yet, the first classifiers for lifespan extension by compounds are now available, learned on intervention data. Here, we review evaluation methodologies and we prioritize training on intervention data whenever available, highlight the importance of safety and toxicity assessments, discuss the role of standardized benchmarks, and present a range of feature processing and predictive modeling approaches. We consider linear and non-linear methods, automated machine learning workflows, and use of AI. We conclude by emphasizing the need for explainable and reproducible strategies, the integration of safety metrics, and the careful validation of predictors based on interventional benchmarks.