Attenuating LRRK2 activity ameliorates progerin-induced aging phenotypes in HGPS models and during physiological aging

The study shows that progerin, the mutant lamin A protein causing HGPS, triggers Rab29-mediated hyperactivation of LRRK2 kinase. Reducing LRRK2 activity in HGPS models rescued morphological, epigenetic, and proteostasis defects, and also ameliorated markers of physiological aging in normal models. This positions LRRK2 inhibitors, already in clinical development for Parkinson's disease, as a candidate repurposing strategy for progeria and age-related decline. Further studies are needed to validate the pathway in vivo and assess long-term safety and efficacy.