International Business Department           Liu Bojia           September 11, 2024

  In our daily life, the occurrence of cancer is associated with a number of risk factors, such as excessive exposure to carcinogenic substances, alcohol consumption, smoking and poor dietary habits, or infection by certain pathogens. We can consciously avoid these risk factors, but there is another risk that we cannot avoid, and that is aging.

  According to statistics from the National Institutes of Health, the incidence of cancer increases steadily with age, with fewer than 25 cancer cases per 100,000 people in the under-20 age group; in the 45-49 age group, the number of cancer cases rises to about 350 per 100,000 people; and in the over-60 age group, the number reaches more than 1,000 per  100,000 people and can rise further with age. increases it can rise further.

  Current research suggests that this phenomenon is due to the fact that as individuals age, they gradually accumulate an excessive burden of genetic mutations or are exposed to excessive environmental triggers. On the other hand, inflammation is also a key driver of cancer development in older individuals, but why does the immune system, which has always worked to protect the body, become an important cancer-promoting factor at a certain age? We still lack evidence for this.

  In a recent paper published in the journal Science, scientists at the Icahn School of Medicine at Mount Sinai, the authors found that as we age, tumours accumulate an excess of myeloid precursor cells, but rather than coming to the rescue, they significantly elevate levels of the inflammatory factor interleukin-1alpha (IL-1alpha).Elevated levels of IL-1alpha increase the destructive inflammatory response and reduce the number of immune cells with anti-tumour activity which in turn promotes tumour growth. The use of anakinra, a drug used in the treatment of rheumatoid arthritis, reduces IL-1α levels and blocks cancer-promoting signals, which provides a novel strategy for tumour treatment in the elderly population.

  In the mouse model, the authors analysed lung tissue from both young and old mice, and they found that the lungs of older mice had increased vascular permeability, while dendritic cells, effector T cells and natural killer (NK) cells, which have a positive immune effect, were reduced, which also made cancer cells more susceptible to immune escape. Indeed, these phenomena were corroborated by the authors' construction of a mouse model of lung tumours, in which tumours in older mice generally progressed faster than those in younger mice under the same tumour-constructing conditions, a discrepancy that is also closely related to the aging immune system.

  In another set of experiments, the study attempted to first perform bone marrow transplants between mice of different ages, followed by tumour construction, and this time the results were different. Younger mice that had been transplanted with bone marrow from older mice ahead of time had significantly faster tumour growth than the control group, and the lung tumours in these younger mice had similar characteristics to older individuals, having fewer cytotoxic T and NK cells. And conversely, in the case of older mice that received bone marrow transplants from younger mice, these older individuals had a much smaller tumour burden, performing comparably to young tumour-bearing mice without additional treatment.

  The authors analysed tumour samples from different age groups separately, and they found that IL-1α levels were significantly increased in tumours from older mice compared to younger individuals, which results from a decline in DNA methyltransferase 3A (DNMT3A) in the haematopoietic system during ageing. ‘This abnormal elevation of inflammatory pathways is destructive and stimulates tumour growth, for example by promoting tumour-associated macrophages and suppressing other immune cells with anti-tumour effects.’ said Matthew D. Park, PhD, corresponding author of the study.

  Expectantly, the researchers found that since cancer risk in old age is closely linked to IL-1α, by blocking this inflammatory pathway they were able to reverse the destructive inflammatory process and slow down tumour progression. As an IL-1 blocker, anabolic acid was sufficient to achieve this effect in mice, which means that the drug also has potential for oncology treatment, particularly to help reduce cancer risk and inhibit tumour progression in the elderly.