T cells and aging (update February 1999)

Abstract

T cell immunosenescence 218effects of dysregulated immune responses in the elderly by supplementation or other approaches may result in an enhancement of their quality of life, and significant reductions in the cost of medical care in old age. FACTORS CONTRIBUTING TO IMMUNO-SENESCENCE HematopoiesisDysregulated hematopoiesis is seen in elderly individuals, raising the possibility that this could contribute to altered immune function in the aged. Hematopoiesis in man may be compromised because of a severely reduced capacity to produce colony stimulating factors (44) and increased production of pro-inflammatory factors such as IL 6 (45), because lower numbers of progenitor cells are present in the BM (46) and because of an age-related decline in proliferative potential of putative haematopoietic stem cells (HSC) (47). In mice, the repopulating potential of murine fetal liver-derived HSC is higher than that of adult BM-derived stem cells (48), suggesting possible aging of the HSC themselves. Normal cells with shorter telomeres possess less remaining replicative capacity than those with longer telomeres (see section 5.2). Accordingly, HSC from adult BM were found to have shorter telomeres than fetal liver-derived or umbilical cord-derived stem cells, consistent with aging of HSC (49). Telomere lengths decreased on culture despite low level expression of telomerase in these cells (50,51), although the rate of basepair loss per population doubling of cells in culture was lower during the first two weeks, when telomerase was upregulated, than in the next two, when it was downregulated (52). The telomerase expressed is therefore functionally active but may not be able to completely maintain telomere length in aging HSC cells. True embryonic stem cells (ESC), on the other hand, which may really be immortal, do retain high levels of telomerase activity (53). On the other hand, ESC from telomerase-knockout mice show gradual telomere shortening over many population doublings (PD) resulting in slowing and eventual cessation of growth (54). Certain animals which do not downregulate telomerase manifest a permanent growth phase and little or no senescence (55,56).

Identification of Immune Responses Against Aldehyde-Modified Peptide Sequences in ApoB Associated With Cardiovascular Disease

“…26 Interestingly, immunosenescence is inhibited by antioxidants indicating involvement of oxidative stress. 27 Immune cells that interact with epitopes in oxidized LDL are likely to be particularly exposed to oxidative stress. Because oxidized LDL is present in arteries already at a very early age 28 these immune response are being continuously challenged for several decades, which may further contribute to a development of immunosenescence.…”

Reduced naïve CD 8 + T ‐cell priming efficacy in elderly adults

“…Age‐related changes in humans have also been described for memory CD8 + T‐cells, which provide frontline defence against viruses and tumors (Appay et al ., 2008). In particular, elderly individuals harbor a higher proportion of terminally differentiated (CD28 − ) memory CD8 + T‐cells, which exhibit strong effector functions constrained by limited proliferative capabilities in tandem with short telomeres (reviewed in Pawelec et al ., 1999). More recently, Akbar and colleagues have provided new insights into the associated molecular defects (Henson et al ., 2014).…”

Cytokine gene polymorphism in human disease: on-line databases

“…320 Little insight to the mechanism of these various effects by the class-II on immune function was available until recently, when it was demonstrated that different class-II molecules varied in the efficiency with which they transduce signals from CD4 across the cell membrane, and that this variation is carried with the intracellular portion of the class-II molecule. 321 As if this were not confusing enough, the age of the donors themselves has been shown to affect T cell activation 322,323 through various mechanisms. In conclusion, the genetic effect seen to be acting on cytokine production, and implicating them as disease-associated loci in their own right, are complicated by the MHC and age.…”