Immunosenescence
Immunosenescence is the gradual deterioration of the
It has been studied in animal models including mice, marsupials and monkeys.
Immunosenescence is not a random deteriorative phenomenon, rather it appears to inversely recapitulate an evolutionary pattern. Most of the parameters affected by immunosenescence appear to be under genetic control.
Age-associated decline in immune function
Aging of the immune system is a controversial phenomenon. Senescence refers to
The major characteristic of the immunosenescent
T cells are not the only immune cells affected by aging:
- telomericshortening.
- The number of phagocytes declines in aged hosts, coupled with an intrinsic reduction of bactericidal activity.[17][18]
- adaptive immune response.
In addition to changes in immune responses, the beneficial effects of
T-cell biomarkers of age-dependent dysfunction
T cells' functional capacity is most influenced by aging effects. Age-related alterations are evident in all T-cell development stages, making them a significant factor in immunosenescence.
- shift in the CD4+/CD8+ ratio[32]
- the accumulation and clonal expansion of memory and effector T cells[8][33]
- impaired development of CD4+ T follicular helper cells (specialized in facilitating peripheral B cell maturation, and the generation of antibody-producing plasma cells and memory B cells)[34]
- deregulation of intracellular signal transduction capabilities[35]
- diminished capacity to produce effector
- shrinkage of antigen-recognition repertoire of T-cell receptor (TcR) diversity[38][39]
- down-regulation of CD28 costimulatory molecules[40]
- cytotoxic activity of NKG2C, etc.) receptors of NK cells[41]
- reduction of cytotoxic activity due to impaired expression of associated molecules such as
- impaired proliferation in response to antigenic stimulation[36][33][38][39]
- accumulation and clonal expansion of memory and effector T cells[8][33]
- hampered immune defences against viral pathogens, especially by cytotoxic CD8+ T cells[37]
- changes in cytokine profile, e.g., increased pro-inflammatory cytokines milieu present in the elderly[43] (IL-6)[10]
- increased PD-1 expression[44]
- glycolysis as a preferential pathway of energetic metabolism - functionally impaired mitochondria produce ROS excessively[45]
- presence of T cell-specific biomarkers of senescence (circular RNA100783, micro-RNAs
Challenges
The elderly frequently present with non-specific signs and symptoms, and clues of focal infection are often absent or obscured by chronic conditions.[2] This complicates diagnosis and treatment.
Vaccination in the elderly
The reduced efficacy of vaccination in the elderly stems from their restricted ability to respond to immunization with novel non-persistent pathogens, and correlates with both CD4:CD8 alterations and impaired dendritic cell function.[48] Therefore, vaccination in earlier life stages seems more likely to be effective, although the duration of the effect varies by pathogen.[49][10]
Rescue of the advanced-age phenotype
Removal of senescent cells with
Immune system aging in mice can be partly restricted by restoring thymus growth, which can be achieved by transplantation of proliferative thymic epithelial cells from young mice.
References
- ^ S2CID 211237913.
- ^ PMID 11580980.
- S2CID 53496572.
- PMID 30305168.
- ^ PMID 20674320.
- ^ PMID 23298609.
- PMID 32117960.
- ^ S2CID 32614875.
- ^ PMID 10689155.
- ^ S2CID 46819839.
- PMID 19541538.
- PMID 18469829.
- PMID 17661905.
- PMID 24769424.
- PMID 35265979.
- ^
High frequency electromagnetic waves such as gamma and xrays can penetrate and damage DNA. Ito K, Hirao A, Arai F, Matsuoka S, Takubo K, Hamaguchi I, et al. (October 2004). "Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells". Nature. 431 (7011): 997–1002. S2CID 4370804.
- S2CID 1898942.
- PMID 15882345.
- S2CID 32717204.
- ^ S2CID 19710282.
- S2CID 11558962.
- S2CID 20498123.
- PMID 18986373.
- PMID 12538685.
- S2CID 1843716.
- S2CID 39130596.
- .
- S2CID 2954461.
- S2CID 8449323.
- S2CID 25042349.
- PMID 15210781.
- PMID 16456027.
- ^ PMID 12393723.
- PMID 22607653.
- S2CID 42659829.
- ^ PMID 17108267.
- ^ S2CID 44591282.
- ^ PMID 15905594.
- ^ PMID 16713964.
- PMID 31181772.
- S2CID 32642259.
- PMID 15661136.
- PMID 9382564.
- PMID 19805226.
- PMID 25083993.
- S2CID 12736294.
- PMID 26451160.
- S2CID 24146051.
- S2CID 21394251.
- PMID 32386656.
- PMID 25870244.
- PMID 27304507.
- PMID 20600832.
- PMID 10617608.
- PMID 30038219.
- PMID 29514064.
- PMID 24556924.