A Discussion on Aging and the Immune System

Immune system degeneration is one of the more important consequences of the accumulating biochemical damage that causes aging. The immune system performs many vital tasks: not just keeping out invading pathogens, but also destroying senescent cells and cancerous cells, amongst other duties. As the immune system grows weak and ineffective, disease becomes a far greater threat, cancer risk rises, and the number of senescent cells increases dramatically.

So-called 'senescent' cells are those that have lost the ability to reproduce themselves. They appear to accumulate in quite large numbers in just one tissue (the cartilage in our joints), but even in these small numbers they appear to pose a disproportionate threat to the surrounding, healthy tissues, because of their abnormal metabolic state. Senescent cells secrete abnormally large amounts of some proteins that are harmful to their neighbours, stimulating excessive growth and degrading normal tissue architecture. These changes appear to promote the progression of cancer.

While the big picture of immune system aging is fairly well defined, many of the details are hazy. As is true for all aspects of human metabolism, researchers are still far from a complete and definitive understanding of the changes that take place over time. Today I'll point you to a very readable open access paper that discusses the present state of knowledge:

In humans, the relationship between aging and the immune response is a complicated one. Aging is characterized by an overall decline in immune function termed immunosenescence, which affects both the innate and adaptive immune systems.

With age, cells of the innate immune system exhibit decreased function; for example, macrophages and neutrophils exhibit a weaker phagocytic response and a weaker oxidative burst. Dendritic cells from older individuals have a decreased ability to stimulate T cells. Cells of the adaptive immune system are also affected by age. T cells in older individuals display decreased T cell memory. There is also a decrease in the naive T cell population in the thymus and decreased B cell production present in the elderly.

Although older individuals have a weaker immune response, conversely, they also display a chronic inflammatory state termed inflammaging, characterized by an increase in inflammatory cytokines present in the serum and an increase in the total NK cell count. Immunosenescence leads to a decreased vaccine response and an increased risk of infection; inflamm-aging could contribute to a host of inflammatory diseases such as atherosclerosis.

Thus, aging can have dramatic effects on the immune response, and conversely, the immune system can affect the risk of many age associated diseases and can therefore affect lifespan. Thus, understanding the relationship between aging and immune system function is of critical importance to human health, particularly as the average human lifespan lengthens, increasing the impact of age-related diseases.

What can be done about the failing immune system? It could - and I think should - be argued that more than enough is known to make inroads into immune system repair for the aged. This is an area with much more fuzziness in the state of knowledge than, say, mitochondrial dysfunction, but clear roads ahead still exist. Some of these are outlined in past posts here at Fight Aging! For example:

In essence, the [adaptive] immune system fails because the thymus, source of immune cells, ceases production and withers away. At the same time, the population of immune cells becomes ever more biased towards memory cells and away from cells capable of fighting new infections - and this is largely due to persistent viruses like cytomegalovirus. Eventually the immune system becomes so focused on the viruses it cannot clear from the body that it has no resources left to perform its other functions.

These problems suggest their own solutions: replace or rejuvenate the thymus, for example, or apply new targeted cell-killing methods developed for cancer therapies to destroy unwanted memory cells. On that note it's worth recalling that thymus transplants have been shown to extend life in mice, but there is plenty of other evidence to support these and similar attempts to restore the aging immune system to youthful levels of activity.

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