# Genomic Perspective on Heterogeneity of Organs and Body Aging

## TL;DR

This review explores how genomic factors contribute to the uneven aging of different organs and the whole body, emphasizing the need for personalized aging interventions.

## Contribution

The paper introduces genomic perspectives as potential mechanisms for heterogeneous organ and body aging.

## Key findings

- Organ-specific aging metrics reveal variability in aging rates across different systems.
- Genomic factors like somatic mutations and epigenetic drift contribute to aging heterogeneity.
- Precision interventions targeting genomic pathways may address organ-specific aging.

## Abstract

Aging is a heterogeneous process, with organ systems and individuals experiencing variable rates of decline that are not fully reflected by chronological age. This variability contributes to the complexity of system morbidity, which poses increasing challenges for clinical care and biomedical research. In this review, we discuss the heterogeneity of organ and whole‐body aging and perspectives on genomics as possible mechanisms that relate to such heterogeneity. We discuss how static genomics, including nuclear genetic variants, and dynamic genetics, such as somatic mutations, epigenetic drifts, and mitochondrial DNA changes might explain the variable rate of aging across organ systems and the whole body. We discuss that the use of metrics that capture heterogeneity in organ and body aging is critical to identify genomic biomarkers of aging, clarifying mechanisms of adaptation versus decline.

Organ‐specific and whole‐body intrinsic aging metrics reveal heterogeneous organ aging, which potentially can arise from the interplay between static germline variation, somatic mutations, epigenetic drift, transposable elements, and mitochondrial DNA changes, highlighting genomic pathways for precision, organ‐targeted aging interventions.