Abstract
With advancing age, immune responses of human beings to external pathogens, i.e., bacteria, viruses,
fungi and parasites, and to internal pathogens - malignant neoplasm cells - become less effective. Two major
features in the process of aging of the human immune system are immunosenescence and inflammaging. The
immune systems of our predecessors co-evolved with pathogens, which led to the occurrence of effective immunity.
However, the otherwise beneficial activity may pose problems to the organism of the host and so it has builtin
brakes (regulatory immune cells) and - with age - it undergoes adaptations and modifications, examples of
which are the mentioned inflammaging and immunosenescence. Here we describe the mechanisms that first created
our immune systems, then the consequences of their changes associated with aging, and the mechanisms of
inflammaging and immunosenescence. Finally, we discuss to what extent both processes are detrimental and to
what extent they might be beneficial and propose some therapeutic approaches for their wise control.
Keywords:
Immune system aging, evolution, immunosenescence, inflammaging, immune cells, senescent cells, human.
[3]
Coventry BJA, Ashdown M, Henneberg M, Davies PCW. The immune system and responses to cancer: coordinated evolution. F1000 Res 2015; 4: 552.
[25]
Franceschi C, Bonafe M, Valensin S, Olivieri F, De LM, Ottaviani E, et al. Inflamm-aging an evolutionary perspective on immunosenescence. Ann N Y Acad Sci 2000; 6/2000(908): 244-54.
[26]
De MM, Franceschi C, Monti D, Ginaldi L. Inflamm-ageing and lifelong antigenic load as major determinants of ageing rate and longevity. FEBS Lett 2005; Nov 4579(10): 2035-9.
[83]
Bryl E, Witkowski JM. Decreased proliferative capability of CD4(+) cells of elderly people is associated with faster loss of activation-related antigens and accumulation of regulatory T cells. Exp Gerontol 2004; 39(4): 587-95.
[85]
Fulop T Jr. Signal transduction changes in granulocytes and lymphocytes with ageing. Immunol Lett 1994; 40(3): 259-68.
[86]
Fulop T Jr, Barabas G, Varga Z, Csongor J, Hauck M, Szucs S, et al. Transmembrane signaling changes with aging. Ann N Y Acad Sci 1992; 673: 165-71.
[93]
Frasca D, Diaz A, Romero M, Blomberg BB. Human peripheral late/exhausted memory B cells express a senescent-associated secretory phenotype and preferentially utilize metabolic signaling pathways. Exp Gerontol 2017; 87(Pt A): 113-20.
[97]
Pawelec G, Larbi A. Immunity and ageing in man: annual review 2006/2007. Exp Gerontol 2008; 43(1): 34-8.
[99]
Naylor K, Li G, Vallejo AN, et al. The influence of age on T cell generation and TCR diversity. J Immunol 2005; 174(11): 7446-52.