Scientists Discover Hidden Molecular Mechanism Behind Age-Related Muscle Weakness

What if ageing muscles become weaker not simply because they are deteriorating, but because they are trying to protect themselves? Scientists have discovered a surprising defence mechanism in ageing muscles that sacrifices strength to protect cells from damage, potentially opening new possibilities for treating age-related muscle loss.

Published in the journal Nature Aging, the study conducted by researchers at the University of Copenhagen investigated how changes in mitochondrial function influence muscle weakness and ageing.

Muscles contain two major types of fibres. Fast-twitch fibres support powerful, rapid movements, while slow-twitch fibres are designed for sustained activity and rely heavily on mitochondria for energy production.

Researchers focused on cardiolipin, a specialised fat molecule essential for maintaining mitochondrial structure and function.

The findings revealed that cardiolipin levels decline in ageing and diseased muscles in both mice and humans, contributing to abnormalities in mitochondrial function.

When researchers experimentally reduced cardiolipin levels in young mice, their muscles began showing changes resembling natural ageing, including a shift from fast-twitch to slow-twitch fibres.

Importantly, restoring cardiolipin to approximately two-thirds of its normal level helped reverse muscle wasting and prevented premature death in the affected mice.

Further experiments revealed that declining cardiolipin increased the production of reactive oxygen species, which triggered a protective transformation in muscle fibres.

A protein called ERRγ helped regulate this response, allowing muscles to adapt to mitochondrial stress.

Researchers also discovered that affected muscles absorbed more glucose and redirected it towards producing antioxidants rather than generating energy, helping protect cells from damage.

Interestingly, antioxidant treatment interfered with this protective adaptation and worsened muscle outcomes in mice.

However, researchers emphasised that the experimental findings were primarily obtained from animal and laboratory studies, hence, further clinical studies are needed to establish their safety and effectiveness.

REFERENCE: Fabian Finger, et al.; Mitochondrial membrane lipid cardiolipin controls fiber-type adaptations in aging muscle via estrogen-related receptor γ. Nature Aging, 2026; 6 (10): 2092 DOI: 10.1038/s43587-026-01227-7