The accelerated ageing of populations underscores the urgency of comprehending the molecular mechanisms underlying ageing. The mTOR protein complex, a pivotal player in numerous bodily processes, particularly in metabolism, has garnered attention for its role in this context.
Recent research on animal models reveals a significant correlation between slight increases in mTOR activity and premature ageing, resulting in a potential reduction in lifespan by up to 20%. This finding sheds light on the connection between mTOR, metabolism, and the onset or exacerbation of ageing-related diseases, particularly in individuals with elevated body mass index, indicative of obesity and inflammation. Furthermore, it elucidates why calorie restriction, a dietary intervention linked to increased animal longevity, may promote healthy ageing by modulating genes that interact with mTOR.
Lead author Alejo Efeyan, from the Metabolism and Cell Signalling Group at the National Cancer Research Centre (CNIO), introduces a novel research tool to explore the interplay between nutrient levels and organ ageing. Published in Nature Aging, the study, with Ana Ortega-Molina as the first author, also involves researchers from various esteemed institutions.
The study unveils a mechanism by which mTOR activity is manipulated through a protein-based system that deceives mTOR regarding nutrient availability within cells. This manipulation triggers cellular dysfunction upon maturity in animals, leading to manifestations of ageing such as dermal thinning and organ damage, notably in the pancreas, liver, and kidneys. Immune responses intended for repair are overwhelmed, exacerbating inflammation and further compromising organ function.
By effectively blocking the immune response responsible for inflammation, researchers observed significant improvements in organ damage, pointing to promising therapeutic avenues for mitigating age-related health decline.
The study’s findings directly translate to human ageing, as evidenced by striking parallels observed in naturally ageing mice. Notably, lysosomal activity, crucial for cellular waste management, diminishes both in naturally aged animals and those with manipulated mTOR activity. This direct correlation underscores the practical relevance of mTOR modulation in the context of ageing and provides valuable insights into potential interventions to ameliorate age-related health decline in humans.
More information: Ana Ortega-Molina et al, A mild increase in nutrient signaling to mTORC1 in mice leads to parenchymal damage, myeloid inflammation and shortened lifespan, Nature Aging. DOI: 10.1038/s43587-024-00635-x
Journal information: Nature Aging Provided by Centro Nacional de Investigaciones Oncológicas – CNIO
