# Markers of Mitochondrial Function and DNA Repair Associated with Physical Function in Centenarians

## TL;DR

This study explores how mitochondrial function and DNA repair relate to physical abilities in centenarians, finding links between these biological markers and physical health.

## Contribution

The study identifies associations between mitochondrial and DNA repair markers and physical function in centenarians, offering new insights into aging mechanisms.

## Key findings

- Centenarians without disabilities had lower mitochondrial respiration and higher mtDNA copy number.
- Grip strength in female centenarians positively correlated with mtDNA copy number and DNA repair enzyme activity.
- Protein carbonylation and BDNF levels showed trends related to physical disability scores.

## Abstract

Mitochondrial dysfunction and genomic instability are key hallmarks of aging. The aim of this study was to evaluate whether maintenance of physical capacities at very old age is associated with key hallmarks of aging. To investigate this, we measured mitochondrial bioenergetics, mitochondrial DNA (mtDNA) copy number and DNA repair capacity in peripheral blood mononuclear cells from centenarians. In addition, circulating levels of NAD+/NADH, brain-derived neurotrophic factor (BDNF) and carbonylated proteins were measured in plasma and these parameters were correlated to physical capacities. Centenarians without physical disabilities had lower mitochondrial respiration values including ATP production, reserve capacity, maximal respiration and non-mitochondrial oxygen-consumption rate and had higher mtDNA copy number than centenarians with moderate and severe disabilities (p < 0.05). In centenarian females, grip strength had a positive association with mtDNA copy number (p < 0.05), and a borderline positive trend for activity of the central DNA repair enzyme, APE 1 (p = 0.075), while a negative trend was found with circulating protein carbonylation (p = 0.07) in the entire cohort. Lastly, a trend was observed for a negative association between BDNF and activity of daily living disability score (p = 0.06). Our results suggest that mechanisms involved in maintaining mitochondrial function and genomic stability may be associated with maintenance of physical function in centenarians.