The short open access review paper noted here sketches a high-level picture of the known components of immune system aging, without going into great detail. The progressive failure of the immune system is a significant component of the frailty that accompanies old age; not only are the elderly vulnerable to pathogens that are easily resisted in youth, but the immune system fails to destroy senescent and potentially cancerous cells, increasing their contribution to aging and mortality risk. Some of this decline is the result of molecular damage after the SENS vision for the treatment of aging, but some is a matter of misconfiguration and limits.
The immune system retains a memory of the pathogens it encounters; that memory can become corrupted in a number of ways, and in the end it simply takes up too much of the limited capacity of the immune system. Capacity is limited in part because the thymus atrophies with age, reducing the supply of new immune cells to a low level in comparison to childhood. In old age, there are too many memory cells, most uselessly specialized to persistent but otherwise minor threats such as cytomegalovirus, and too few cells capable of tackling new pathogens. This part of the problem at least might be solved in the near future through selective destruction of misconfigured or damaged immune cells, and their replacement with new cells cultured from a patient blood sample.
Human aging is characterized by both physical and physiological frailty. With progressive age, the immune system and the propensity for abnormal immunity change fundamentally. Aging is associated with a decline in multiple areas of immune function. Aging is associated with a sort of paradox: a state of increased autoimmunity and inflammation coexistent with a state of immunodeficiency. Immunosenescence is a new concept that reflects the immunological changes associated with age. There are three theories that explain the phenomenon of immunosenescence.
According to the autoimmune theory of aging, the immune system tends to lose efficiency and experiences widespread dysfunction, evidenced by autoimmunity (immune reactions against one’s own body proteins). Two age-related processes cause autoimmune diseases: (i) different rates of senescent cell accumulation in the immune system and target tissue/organ and heterogeneous accumulation of senescent cells in tissues/organs. Separately or combined, these two processes are at the base of autoimmune diseases. The production of autoantibodies has been hypothesized to be secondary to thymus involution with a decline of naïve T cells and the accumulation of clonal T cells with activation due to “neoantigens” during the aging process.
With advancing age the body is unable to defend itself from pathogens and results in a detrimental harm; this is the focus of immunodeficiency theory. Clinical evidence indicates that with advancing age, immune responses against recall antigens may still be conserved, but the ability to mount primary immune responses against novel antigens declines significantly. The impaired ability to mount immune responses to new antigens may result in a high susceptibility to infectious diseases. The immune responses to novel antigens rely on the availability of naive T cells. Together with the age-related thymic involution, and the consequent age-related decrease of thymic output of naive CD8+ T-cell reservoir, this situation leaves the body practically devoid of naive T cells, and thus likely more prone to a variety of infectious and non infectious diseases.
Ageing is associated with various changes in immune parameters, therefore many authors have postulated that these age-related diseases could be explained, at least in part, by an overall deregulation in the immune system response, leading to a deregulation theory of immune system aging. This is supported by an age-associated disruption to the balance of alternatively expressed isoforms for selected genes, suggesting that a modification of the mRNA processing may be a feature of human aging. The observed down regulation of toll-like receptors (TLRs) and nod-like receptors (NLRs) during the aging process may contribute to the lack of effective recognition of invading pathogens or the commensal flora. This effect results in aberrant secondary immune cell activation and could significantly contribute to morbidity and mortality at an advanced age.