Muscles become weaker with age as mitochondrial function gradually declines. At the same time, aging muscles undergo a shift from fast-twitch fibers, which provide short bursts of power, toward slow-twitch fibers that are more dependent on mitochondria. Researchers have identified a potential mechanism that may explain this seemingly paradoxical change.

The study focused on cardiolipin, a specialized lipid located in the inner membrane of mitochondria that is essential for maintaining their structure and function. The researchers found that cardiolipin levels decline in muscle mitochondria with aging and disease in both mice and humans, contributing to mitochondrial damage and impaired performance.

When cardiolipin levels were reduced in young mice, the animals developed a fast-to-slow muscle fiber transition similar to that seen during aging. Restoring cardiolipin to approximately two-thirds of normal levels helped reverse muscle wasting and prevented premature death in the animals.

The researchers found that the shift toward slow-twitch fibers may actually serve as a protective response to mitochondrial stress. Reduced cardiolipin increases reactive oxygen species (ROS), which can damage cells but also act as signaling molecules. This process activates ERRγ, a protein that promotes mitochondrial remodeling and drives the transition toward slow-twitch fibers.

The remodeled muscle fibers also altered how they used glucose. Instead of primarily burning the additional glucose for energy, cardiolipin-deficient muscles redirected it toward producing antioxidants, helping protect cells from oxidative stress.

The findings highlight cardiolipin and ERRγ as potential targets for addressing age-related muscle decline. Although the research was conducted primarily in mice, analysis of human muscle samples confirmed that cardiolipin levels also decrease with age. Further studies are needed to determine whether targeting these pathways could support healthier muscle aging in humans.

Source: https://www.news-medical.net/news/20260929/Targeting-specific-nuclear-receptor-could-help-preserve-aging-muscle-function.aspx