How does aging affect cancer cell aggression?

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Aging Increases Cancer Cell Aggression Through Methylmalonic Acid Accumulation

The aging process can significantly enhance cancer cell aggression, leading to increased migratory and invasive capabilities, as well as drug resistance. This phenomenon is linked to the accumulation of methylmalonic acid (MMA), a metabolic byproduct, in the body as individuals age. Research indicates that MMA can reprogram cancer cells, promoting a more aggressive and metastatic behaviour.
Accumulation of Methylmalonic Acid with Age

As individuals age, the metabolic byproduct methylmalonic acid (MMA) tends to accumulate in the body. This accumulation is a natural consequence of metabolic processes that occur over time. Studies have observed that blood samples from donors aged 60 and older contained higher levels of MMA compared to those from younger donors aged 30 and under.
Impact of Aged Blood on Cancer Cells

Exposure to blood from older donors (60+) significantly altered the behaviour of cancer cells. When lung and breast cancer cells were exposed to blood from these older individuals, they exhibited a marked increase in their migratory and invasive capacities. Furthermore, these cells developed resistance to two commonly used cancer drugs, suggesting a heightened resilience to treatment.
Mechanism of Increased Aggression via SOX4 Gene

The research identified a key mechanism through which MMA influences cancer cells: the activation of the SOX4 gene. MMA appears to reprogram cancer cells by switching on SOX4, a gene previously shown to promote aggression and metastasis in cancer. When the expression of SOX4 was blocked, MMA lost its ability to induce the observed changes in cancer cells, including their resistance to drug treatments.
Potential Implications for Cancer Treatment

The findings suggest that reducing MMA levels could be a potential strategy to mitigate cancer mortality. Given that MMA accumulation is linked to high-protein diets, a low-protein diet might theoretically improve a patient's response to cancer treatments. Further research is ongoing to explore therapies aimed at reducing MMA levels, which could offer new avenues for managing aggressive cancers.

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How does aging affect cancer cell aggression?

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