A novel study conducted by the Spanish National Cancer Research Centre (CNIO) has found that ageing is sped up in animal cells that ‘perceive’ themselves to contain too many nutrients, even when the animal is following a regular diet — which can lead to organ inflammation and malfunction.
The findings have been published in Nature Aging, and suggest that intervening in this inflammation can relieve symptoms and enhance cell survival.
The results were discovered through research on animal models, though when comparing blood samples from the elderly, it appears that this can also be extended to humans.
mTOR’s role in ageing and inflammation
The mTOR protein complex has been implicated in many contexts in the normal functioning of the body, with a key role being in the regulation of metabolism.
Results from this trial have found that when mTOR activity is even slightly increased, symptoms of ageing are exacerbated… shortening the lifetime of an animal by up to 20%.
Because mTOR is heavily involved in metabolic homeostasis, the researchers suggest that it may be a contributing factor to why ageing-related diseases are exacerbated in those with a high body mass index (BMI) — a factor associated with obesity and the presence of inflammation.
The study
During the study, researchers modulated the activity of a protein associated with the mTOR protein complex to determine if a high prevalence of nutrients in the cell had any impact on mTOR signalling.
To do this, they genetically modified the protein associated with nutrient signalling — RagC — meaning it would falsely signal a high level of nutrients to mTOR.
Because of this, mTOR was activated in the same way as if a cell was receiving too many nutrients, enabling the investigators to determine the impact of this type of cell signalling on ageing and inflammation.
Mitigating chronic inflammation could be a potential therapeutic measure
The results
From observing animals after this modulation to RagC, it was seen that once they reach maturity, their organ functionality begins to fail and the characteristic symptoms of ageing begin to appear — which can be seen in crucial regions like the pancreas, liver and kidneys.
However, when they blocked the inflammatory response that's generally associated with ageing, it was seen that there was reduced damage to the cells.
Because of this, Ana Ortega-Molina, head of the Metabolism in Cancer and Ageing Laboratory at CBM and lead of this study, believes that mitigating chronic inflammation could be "a potential therapeutic measure that controls deterioration of health in ageing populations”.
Does this relate to human ageing?
Although this study was conducted on animal models, the results appear to align with the natural human ageing process.
When the University of Valencia looked at blood samples from young people and septuagenarians, they found a significant decrease in the presence of lysosomes, which is a common biomarker of ageing.
Dr Ortega-Molina and her team confirmed this same phenomenon was happening in the animal models, as both the mice that were genetically modified to induce ageing and those who were allowed to naturally age exhibited reduced lysosomal activity.
Alejo Efeyan, head of the Metabolism and Cell Signalling Group at the National Cancer Research Centre (CNIO), commented: “The finding of our study offers ample fertile ground to ask more questions about how nutrient — or its signalling — impacts different organs and their ageing. It also suggests we should investigate how this comes into the onset of neurodegenerative diseases.”
