HDAC11 deficiency improves muscle function and regeneration during ageing

A new study led by the Badalona Neuromuscular Research Group (GRENBA) at the Germans Trias i Pujol Research Institute (IGTP) has identified the HDAC11 protein, an enzyme involved in cellular regulation, as a new potential therapeutic target for the treatment of sarcopenia. Published in the journal GeroScience, the study shows that HDAC11 deficiency in aged murine models reduces muscle mass loss, promotes muscle regeneration following injury and improves overall muscle function.

Sarcopenia, the progressive loss of muscle mass and function associated with ageing, negatively impacts the quality of life of the elderly population. The study demonstrates that the absence of HDAC11 reduces muscle atrophy, preserves the muscle stem cell reservoir, decreases alterations in neuromuscular junctions and promotes muscle regeneration. Furthermore, at the metabolic level, HDAC11-deficient muscles exhibit improved fatty acid oxidation and a more favourable lipid composition.

"Currently, the global population is progressively ageing, with estimates suggesting that nearly a quarter of the world's population will be over 65 years old by 2050, which will have a significant social and economic impact," explains Dr Mònica Suelves, principal investigator of the study, together with PhD student Renato Odria. "Maintaining muscle mass and function is key to ensuring a good quality of life during ageing, yet available treatments to prevent or reverse sarcopenia remain very limited. Studies like ours help to better understand the biological mechanisms of age-related muscle loss and propose new therapeutic strategies to support healthy ageing."

Research in geroscience, an emerging field that investigates the biological mechanisms of ageing and its associated diseases, enables the identification of molecular factors that either accelerate or slow down ageing. "Our results show for the first time that HDAC11 can be considered a gerogene, a gene that promotes ageing, and we propose it as a new therapeutic target to reduce sarcopenia," adds Dr Suelves.

The findings suggest that the selective inhibition of HDAC11, for which specific compounds have already been developed, could represent a new strategy to slow down age-related muscular decline and promote healthier ageing.