New research from the University of Barcelona has unveiled a groundbreaking discovery that could prevent the decline of brown adipose tissue activity as individuals age. This decline contributes to obesity and chronic cardiovascular diseases, making this finding particularly urgent and relevant for an aging population.
The study, led by Professor Joan Villarroya, identifies a critical molecular mechanism that plays a role in the loss of brown fat activity over time. Published in the journal Science Advances, the research indicates that enhancing a process known as chaperone-mediated autophagy (CMA) could be key in maintaining metabolic health as we grow older.
Brown adipose tissue is vital for thermogenesis, the process of generating heat from fat, and is crucial in protecting against obesity, type 2 diabetes, and cardiovascular diseases. As aging progresses, the activity of this tissue diminishes, leading to increased risks of metabolic disorders. The latest findings show that the thermogenic activation of brown fat is linked to an increase in CMA, which selectively degrades certain proteins that repress fat activity.
According to Villarroya, “Acting on chaperone-mediated autophagy may play a key role in modulating tissue activity.” This is particularly significant as research suggests that the decline in CMA during aging leads to a loss of brown adipose tissue functionality.
For years, scientists have been attempting to develop drugs that can activate brown fat, but previous options came with unwanted side effects. The study reveals that new experimental drugs aimed at enhancing CMA show promise. In trials with aging mice, these drugs successfully maintained brown fat activity and improved metabolic function.
“Effective experimental drugs are now beginning to emerge to modulate chaperone-mediated autophagy,” Villarroya stated. This pivotal research opens the door for potential treatments targeting low brown adipose tissue activity in humans, especially for conditions like obesity and diabetes.
Currently, some preclinical drugs designed for neurodegenerative diseases may also be repurposed to boost CMA. These developments are vital as they could help prevent the inactivation of brown fat associated with aging. The research team is actively exploring how to harness CMA to enhance metabolic energy expenditure, aiming to mitigate obesity and its severe cardiometabolic impacts.
“Research is ongoing in both experimental models and initial studies in patients, with collaborations across several hospitals,” Villarroya concluded.
This urgent study signals a significant step forward in understanding how to maintain metabolic health and combat the chronic diseases that often accompany aging. As the population ages, the implications of this research could be transformative for public health.
For more detailed insights, see the full study: Alberto Mestres-Arenas et al, Chaperone-mediated autophagy controls brown adipose tissue thermogenic activity, Science Advances (2025). DOI: 10.1126/sciadv.ady0415.
