Contemplating the Causes of Immunosenescence

The immune system is vital for many reasons. It is not just a barrier against pathogens of all sorts, such as bacteria, fungi, and viruses, but also a watchdog that hunts down and destroys harmful cells, such as those that have entered senescence or are in danger of becoming cancerous. In later life the immune system declines and fails in characteristic ways, partly a consequence of its evolved structure and resource limits, and partly the same general accumulation of damage that affects all cells in the body. The failure of the immune system is important because it contributes to other threads in aging: allowing senescent cells to build up, failing to catch cancers when they can be easily destroyed, and generating ever higher levels of inflammation. This increasing incapacity alongside increasing inflammation is known as immunosenescence or inflammaging.

Here is an open access paper on the subject:

Hallmarks of human "immunosenescence": adaptation or dysregulation?

Is immunosenescence an intrinsic ageing process leading to dysregulation of immunity or an adaptive response of the individual to pathogen exposure? Age-associated differences in bone marrow immune cell output and thymic involution suggest the former. Accepted hallmarks of immunosenescence (decreased numbers and percentages of peripheral naïve T cells, especially CD8+ cells, and accumulations of memory T cells, especially late-stage differentiated CD8+ cells) suggest the latter, viewed as the result of depletion of the reservoir of naïve cells over time by contact with pathogens and their conversion to memory cells, the basis of adaptive immunity.

Thymic involution beginning early in life limits the generation of naive cells such that the adult is believed to rely to a great extent on the naïve cell pool produced mostly before puberty. Thus, these hallmarks of immunosenescence would be markedly affected by the history of the individual's exposure to pathogens, [and] in humans, particularly to infection with CMV.

...

One very striking difference [between industrialized Western populations and those of poorer regions is that in] the "wild-type" situation, all humans are infected with CMV from the age of ca. 2 months on, when they no longer receive only anti-CMV antibody in the mother's milk, but also the infectious virus that has reactivated in the meantime. CMV-negativity is an artifact of civilization, hygiene and decreased breast feeding. Hence, in our pilot study of young and old men in rural Pakistan, all the young were already CMV-positive. As "old" is viewed as [greater than] 50 years in this society, we sought to establish whether age-associated differences in immune phenotypes that we and others had established in older European and US populations were similar in Pakistanis, and whether they manifested earlier in the latter.

We concluded that there were two major differences between the Pakistani population and the historical controls of [subjects from Western, industrialized regions]. One was that we did indeed see age-associated differences in CD8+ T cells earlier in the Pakistanis, and the other was that we saw for the first time in a healthy population that not only the CD8+ subset but also the CD4 + T cells were affected. This we had otherwise only seen in pathological European populations, eg. those with Alzheimer's. We interpret this to mean that the level of "antigenic stress" in the Pakistani population, old at 50, could indeed be leading to "premature immunosenescence".

Some thoughts on what can be done to reverse some of the declines in the aging immune system - alongside a few concrete results in laboratory animals - can be found a little way back in the Fight Aging! archives.

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