Nature: Can the accumulation of specific metabolites in aging individuals promote tumor progression?

From the age of 65, the risk of cancer and associated mortality in humans has increased significantly.
, however, our understanding of the complex relationship between age and cancer is still in its infancy.
decades, this link has been largely attributed to increased exposure to mutagents in older persons.
, however, does not take into account the established role of diet, exercise and small molecules that target metabolic aging.
given the growing evidence that the external factors of cancer cells are key to regulating tumor progress, the researchers hypothesically assume that aging may create a systematic environment that supports tumor progress and aggressiveness.
in a recent paper published in the journal Nature, researchers used the serum to obtain human serum (HS) from 30 young (aged 30) and 30 healthy contributions (aged 60) and culture human cancer A549 and HCC1806 cells with that serum.
have shown that inflammatory factors play a key role in tumor progression and contribute to the development of age-related diseases.
, however, proteomics analysis of aging serums did not show a common inflammatory trait, explaining the aggressive properties observed by researchers in cancer cells.
the effectiveness of metabolic interventions, such as diet, exercise and calorie restriction, can reduce cancer susceptibility and progression, the researchers examined the metabolic composition of the serum of the body.
of the 179 circulating metabolites detected by targeted metabolomics, only 10 metabolite changes were statistically significant (double-sided t-test, P 0.5).
considering the known or recommended role of the following four metabolites in the aging process, a significant decrease in levels of glutathione, arginine, glutamine and alpha-ketone diacine is expected.
note that only three metabolites continue to increase in the serum of older patients: phosphate acetone, quinac acid and methyl propylene acid (MMA).
to test whether any of the three metabolites were responsible for inducing cancer progression, the researchers treated A549 cells with each metabolite.
only MMA can induce a complete emT-like esopat that promotes cancer progression, including e-cadherin decline, while fibrin and vimentin proteins increase.
, metabolic changes that occur with age can produce a systemic environment conducive to tumor progression and aggression.
also traced MMA's ability to induce SOX4 expression, causing transcription reprogramming and making cancer cells aggressive.
, the accumulation of MMA represents a link between aging and cancer progress, suggesting that MMA is a promising target for treatment for advanced cancer.
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