Читать книгу Pathy's Principles and Practice of Geriatric Medicine - Группа авторов - Страница 48

The term immunosenescence is not restricted to senescence (as a component of biological ageing described earlier) of immune cells but encompasses all immune system modifications that characterise ageing. Components of biological ageing discussed in this chapter are probably synergistic in reducing functions of several physiologic systems, thus contributing to different phenotypes of ageing. Among these physiologic systems, we propose here to emphasise the role of the immune system for two reasons.

First, a major feature of the biology of ageing is chronic low‐grade inflammation (also called inflammageing ⁶¹), thought to contribute to age‐related diseases and ageing phenotypes.⁶² Known causes of this inflammation are other components of biological ageing (mitochondrial dysfunction, cell senescence, loss of proteostasis, epigenetic alterations) and extrinsic factors (chronic infections and changes in microbiota).⁶³ Thus, one could argue that inflammation is more of a bystander consequence than a phenomenon that contributes to ageing. Despite associations between higher levels of inflammatory cytokines, age‐related diseases, and mortality, it is still somewhat unclear how (and even whether) chronic low‐grade inflammation contributes to the ageing process. Nevertheless, ageing mice lacking proteins of the inflammasome pathway exhibit less decline in immune, physical, and cognitive functions than wild‐type mice,^64,65 and this pathway is involved in Alzheimer’s disease pathophysiology.⁶⁶ In addition, if we consider inflammation as a common link between several components of biological ageing and phenotypes of ageing, it becomes an interesting target for intervention. In line with this, drugs specifically designed to block pro‐inflammatory cytokines, such as interleukin‐1β, have reduced the incidence of age‐related diseases in humans.^67,68

Second, as the function of the immune system is to maintain homeostasis, it is easy to conceive that defects in this system will exacerbate detrimental effects of other components of biological ageing by failure to eliminate not only pathogens but also pre‐malignant cells, senescent cells, and misfolded proteins. Thus, its contribution to age‐related diseases and ageing phenotypes may be far broader than the usually cited infections, cancers, and auto‐immunity. Both the innate and adaptive arms of the immune system exhibit multiple functional changes with ageing.⁶⁹ The primary characteristics of the ageing innate immune arm are immune stimulation at the basal level and immune paralysis when specific functions are needed,⁷⁰ a paradox proposed to constitute the basis of inflammageing. Regarding the adaptive arm, ageing of both B and T cell compartments is mainly characterised by a decreased number of naïve cells able to respond to new challenges and inflation of the pool of memory cells, with shrinkage of their antigenic repertoire.^71,72 These changes have been linked to components of biological ageing cited earlier as well as to long‐term exposure to antigens of persistent infective agents, such as cytomegalovirus.^73,74