Cancer in old age is made more aggressive by molecules in the blood

A molecule that builds up in the blood of older people through the metabolism of proteins and fats can promote cancer in old age. It gives cancer cells the ability to spread from one place in the body to another and, accordingly, to form metastases. In their study, researchers report that methylmalonic acid (MMS), which is a by-product of protein and fat digestion, enables tumors to spread.

Why does the risk of cancer increase with age?

Researcher examines blood sample of aged cancer through test tube in laboratory

The risk of developing cancer increases with age as people accumulate genetic mutations and are constantly exposed to cancer-causing substances. Most cancer-causing agents are found in the environment, but some are produced by the body. MMS was found in very small amounts in the blood cells of young people. Usually this binds to the molecule coenzyme A to form methylmalonyl coenzyme. In a reaction, it is then converted into succinyl coenzyme. Vitamin B 12 also plays a role as a cofactor. The succinyl-CoA then enters the tricarboxylic acid cycle. This is a series of chemical reactions that are integral to the production of energy in the cell. In some diseases, the body cannot metabolize MMS efficiently, resulting in toxic build-up in the blood. The metabolic disorder methylmalonic acidemia occurs, for example, as a result of the failed conversion of methylmalonyl-CoA to succinyl-CoA due to genetic defects in key enzymes or a vitamin B 12 deficiency.

red blood cells in bloodstream shown in 3d

In addition, the researchers report that the levels of methylmalonic acid in the blood of healthy people over 60 are significantly higher than in people under 30 years of age. The increased MMS level had also not caused any cancer in the people examined. However, the authors found that treating human cancer cells with serum from the elderly group’s blood or with high levels of MMS caused them to take on characteristics of metastatic cancer cells. These are those that can spread from a primary tumor to seed cancer elsewhere in the body. These characteristics include a loss of cell-cell attachment and an increase in mobility. When injected into laboratory mice, the cells formed metastatic tumors in the lungs.

Study results

female doctor examines patients with mrt in hospital

All subjects in this study who had high plasma MMS levels appeared to be cancer free. This suggests that the effects of the molecule are due to the spread of cancer in the body rather than the initial cancer formation. The development and spread of cancer are different processes that involve different molecular mechanisms. Future studies may confirm whether MMS specifically affects metastasis in humans in the same way. This molecule is different from many previously known age-related causes of cancer, including environmental factors and genetic mutations. Further research into the timing of the effects of MMS could then determine the optimal timing for therapeutic use of MMS inhibitors if they become available.

A final question is how MMS stimulates changes in gene expression associated with metastasis at the molecular level. The authors of the study hypothesized that MMS activates the transcription of the TGF-β2 gene. However, it remains to be seen how MMS amplifies this transcription. Answers to these questions will advance an understanding of metabolic changes and their role in the development of cancer. Regardless of the answers, the study broadened our view of cancer risk factors by drawing attention to the role of metabolism in age-related cancer development.

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