# Omega-3 dietary supplementation combined with exercise to keep telomere integrity in the liver of aged obese female mice

## TL;DR

Combining omega-3 supplements and exercise helps protect liver telomeres in aged obese female mice, potentially slowing aging-related damage.

## Contribution

The study shows that combining DHA and exercise is uniquely effective in preventing telomere shortening in aged obese mice.

## Key findings

- Combining DHA and exercise prevented telomere attrition in aged obese mice.
- Only the combined DHA and exercise group improved genes related to oxidative stress.
- DHA and exercise separately reduced pro-inflammatory cytokine Il-1b expression.

## Abstract

Telomere shortening is a key marker of cellular aging and linked to pathologies such as liver disease. Oxidative stress and inflammation (hallmarks of obesity) contribute to telomere shortening, while omega-3 (DHA) and exercise may counteract these effects by enhancing cellular homeostasis. This study aims to analyze the influence of DHA supplementation and/or exercise over one year on liver telomere length in obese aged mice. Two-month-old female mice were fed either a control or high-fat diet (HFD) for four months. Diet-induced obese (DIO) mice were then assigned to one of four groups: (1) DIO, maintained on an HFD; (2) DIO + EX, subjected to exercise; (3) DIO + DHA, fed an HFD supplemented with DHA; and (4) DIO + DHA + EX, subjected to both exercise and DHA supplementation. The intervention continued until the mice reached 18 months of age. The DIO group showed significant telomere attrition, which was prevented only when omega-3 and exercise were combined. Additionally, only the combined DHA and exercise group improved the expression of genes related to oxidative stress (Sirt3, Foxo3, Sod1, Cat). Interestingly, DHA and exercise separately reduced pro-inflammatory cytokine Il-1b expression compared to the control group, but not when combined. These results indicate that DHA combined with physical exercise could be an effective strategy to maintain telomere integrity in aged obese female mice, due to their antioxidant properties.

The online version contains supplementary material available at 10.1007/s13105-026-01139-5.

Telomere attrition contributes to liver disease progression.

Omega-3 and exercise could slow telomere shortening in obese aged mice.

DHA supplementation and exercise may stimulate Sod1 and Cat expression.

The online version contains supplementary material available at 10.1007/s13105-026-01139-5.