Immunological Aspects of Age-related Diseases

Overview

Journal World J Biol Chem

Publisher Baishideng Publishing Group

Specialty Biochemistry

Date 2017 Jun 8

PMID 28588756

Citations 11

Authors

Ken-Ichi Isobe

Naomi Nishio

Tadao Hasegawa

Affiliations

Soon will be listed here.

Abstract

The proportion of elderly people rises in the developed countries. The increased susceptibility of the elderly to infectious diseases is caused by immune dysfunction, especially T cell functional decline. Age-related hematopoietic stem cells deviate from lymphoid lineage to myeloid lineage. Thymus shrinks early in life, which is followed by the decline of naïve T cells. T-cell receptor repertoire diversity declines by aging, which is caused by cytomegalovirus-driven T cell clonal expansion. Functional decline of B cell induces antibody affinity declines by aging. Many effector functions including phagocytosis of myeloid cells are down regulated by aging. The studies of aging of myeloid cells have some controversial results. Although M1 macrophages have been shown to be replaced by anti-inflammatory (M2) macrophages by advanced age, many human studies showed that pro-inflammatory cytokines are elevated in older human. To solve this discrepancy here we divide age-related pathological changes into two categories. One is an aging of immune cell itself. Second is involvement of immune cells to age-related pathological changes. Cellular senescence and damaged cells in aged tissue recruit pro-inflammatory M1 macrophages, which produce pro-inflammatory cytokines and proceed to age-related diseases. Underlying biochemical and metabolic studies will open nutritional treatment.

Citing Articles

Are immunosenescent T cells really senescent?.

Slaets H, Veeningen N, de Keizer P, Hellings N, Hendrix S Aging Cell. 2024; 23(10):e14300.

PMID: 39113243 PMC: 11464117. DOI: 10.1111/acel.14300.

Reduced insulin/IGF-1 signalling upregulates two anti-viral immune pathways, decreases viral load and increases survival under viral infection in C. elegans.

Duxbury E, Carlsson H, Kimberley A, Ridge Y, Johnson K, Maklakov A Geroscience. 2024; 46(6):5767-5780.

PMID: 38589671 PMC: 11493891. DOI: 10.1007/s11357-024-01147-7.

Towards a better preclinical cancer model - human immune aging in humanized mice.

Tan J, Hwang Y, Chin H, Liu M, Tan S, Chen Q Immun Ageing. 2023; 20(1):49.

PMID: 37752597 PMC: 10523735. DOI: 10.1186/s12979-023-00374-4.

Functional conservation in genes and pathways linking ageing and immunity.

Fabian D, Fuentealba M, Donertas H, Partridge L, Thornton J Immun Ageing. 2021; 18(1):23.

PMID: 33990202 PMC: 8120713. DOI: 10.1186/s12979-021-00232-1.

Effects of sex, age, and season on the variation of blood analytes in a clinically healthy population of bottlenose dolphins ( spp.).

Nollens H, Haney N, Stacy N, Robeck T Vet Q. 2020; 40(1):342-352.

PMID: 33138727 PMC: 7733981. DOI: 10.1080/01652176.2020.1845415.

References

Morrison S, Wandycz A, Akashi K, Globerson A, Weissman I . The aging of hematopoietic stem cells. Nat Med. 1996; 2(9):1011-6. DOI: 10.1038/nm0996-1011. View

Radford D, Wang K, McNelis J, Taylor A, Hechenberger G, Hofmann J . Dehydroepiandrosterone sulfate directly activates protein kinase C-beta to increase human neutrophil superoxide generation. Mol Endocrinol. 2010; 24(4):813-21. PMC: 5417533. DOI: 10.1210/me.2009-0390. View

Hoeffel G, Wang Y, Greter M, See P, Teo P, Malleret B . Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac-derived macrophages. J Exp Med. 2012; 209(6):1167-81. PMC: 3371735. DOI: 10.1084/jem.20120340. View

Nishio N, Okawa Y, Sakurai H, Isobe K . Neutrophil depletion delays wound repair in aged mice. Age (Dordr). 2009; 30(1):11-9. PMC: 2276589. DOI: 10.1007/s11357-007-9043-y. View

Liang Y, van Zant G, Szilvassy S . Effects of aging on the homing and engraftment of murine hematopoietic stem and progenitor cells. Blood. 2005; 106(4):1479-87. PMC: 1895199. DOI: 10.1182/blood-2004-11-4282. View

Nathan C . Neutrophils and immunity: challenges and opportunities. Nat Rev Immunol. 2006; 6(3):173-82. DOI: 10.1038/nri1785. View

Childs B, Baker D, Wijshake T, Conover C, Campisi J, van Deursen J . Senescent intimal foam cells are deleterious at all stages of atherosclerosis. Science. 2016; 354(6311):472-477. PMC: 5112585. DOI: 10.1126/science.aaf6659. View

Kohler S, Wagner U, Pierer M, Kimmig S, Oppmann B, Mowes B . Post-thymic in vivo proliferation of naive CD4+ T cells constrains the TCR repertoire in healthy human adults. Eur J Immunol. 2005; 35(6):1987-94. DOI: 10.1002/eji.200526181. View

Pang W, Price E, Sahoo D, Beerman I, Maloney W, Rossi D . Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age. Proc Natl Acad Sci U S A. 2011; 108(50):20012-7. PMC: 3250139. DOI: 10.1073/pnas.1116110108. View

10.

Wang M, Jiang L, Monticone R, Lakatta E . Proinflammation: the key to arterial aging. Trends Endocrinol Metab. 2013; 25(2):72-9. PMC: 3917314. DOI: 10.1016/j.tem.2013.10.002. View

11.

Hashimoto D, Chow A, Noizat C, Teo P, Beasley M, Leboeuf M . Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes. Immunity. 2013; 38(4):792-804. PMC: 3853406. DOI: 10.1016/j.immuni.2013.04.004. View

12.

Blackman M, Woodland D . The narrowing of the CD8 T cell repertoire in old age. Curr Opin Immunol. 2011; 23(4):537-42. PMC: 3163762. DOI: 10.1016/j.coi.2011.05.005. View

13.

Rubinsztein D, Marino G, Kroemer G . Autophagy and aging. Cell. 2011; 146(5):682-95. DOI: 10.1016/j.cell.2011.07.030. View

14.

Henry C, Marusyk A, DeGregori J . Aging-associated changes in hematopoiesis and leukemogenesis: what's the connection?. Aging (Albany NY). 2011; 3(6):643-56. PMC: 3164372. DOI: 10.18632/aging.100351. View

15.

Spits H, Artis D, Colonna M, Diefenbach A, Di Santo J, Eberl G . Innate lymphoid cells--a proposal for uniform nomenclature. Nat Rev Immunol. 2013; 13(2):145-9. DOI: 10.1038/nri3365. View

16.

Beerman I, Bhattacharya D, Zandi S, Sigvardsson M, Weissman I, Bryder D . Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion. Proc Natl Acad Sci U S A. 2010; 107(12):5465-70. PMC: 2851806. DOI: 10.1073/pnas.1000834107. View

17.

Aspinall R, Andrew D . Thymic involution in aging. J Clin Immunol. 2000; 20(4):250-6. DOI: 10.1023/a:1006611518223. View

18.

Chorro L, Sarde A, Li M, Woollard K, Chambon P, Malissen B . Langerhans cell (LC) proliferation mediates neonatal development, homeostasis, and inflammation-associated expansion of the epidermal LC network. J Exp Med. 2009; 206(13):3089-100. PMC: 2806478. DOI: 10.1084/jem.20091586. View

19.

Bruunsgaard H, Andersen-Ranberg K, Jeune B, Pedersen A, Skinhoj P, Pedersen B . A high plasma concentration of TNF-alpha is associated with dementia in centenarians. J Gerontol A Biol Sci Med Sci. 1999; 54(7):M357-64. DOI: 10.1093/gerona/54.7.m357. View

20.

Vicente R, Mausset-Bonnefont A, Jorgensen C, Louis-Plence P, Brondello J . Cellular senescence impact on immune cell fate and function. Aging Cell. 2016; 15(3):400-6. PMC: 4854915. DOI: 10.1111/acel.12455. View