Accelerated Aging versus Rejuvenation of the Immune System in Heterochronic Parabiosis

Abstract

The emergence of immune disorders in aging is explained by many factors, including thymus dysfunction, decrease in the proportion and function of naïve T cells, and so forth. There are several approaches to preventing these changes, such as thymus rejuvenation, stem cells recovery, modulation of hormone production, and others. Our investigations of heterochronic parabiosis have shown that benefits of a young immune system, e.g., actively working thymus and regular migration of young hematopoietic stem cells between parabiotic partners, appeared unable to restore the immune system of the old partner. At the same time, we have established a progressive immune impairment in the young heterochronic partners. The mechanism of age changes in the immune system in this model, which may lead to reduced life expectancy, has not been fully understood. The first age-related manifestation in the young partners observed 3 weeks after the surgery was a dramatic increase of CD8(+)44(+) cells population in the spleen. A detailed analysis of further changes revealed a progressive decline of most immunological functions observable for up to 3 months after the surgery. This article reviews possible mechanisms of induction of age-related changes in the immune system of young heterochronic partners. The data obtained suggest the existence of certain factors in the old organisms that trigger aging, thus preventing the rejuvenation process.

Homeostatic migration and distribution of innate immune cells in primary and secondary lymphoid organs with ageing

“…in the case of impaired Schwann cell function [17], impaired T cell subset distribution [18], function [19] and thymic involution [18,20], and in the first two examples pro-geronic effects were noted in the adult animal. Regarding individual pro-geronic molecules, increased levels of CCL11 and b2m with age are associated with decreased brain functions [8,11] and increased b-catenin signalling was implicated in defects in bone repair [14].…”

“…With regard to ageing of the immune system, Pishel et al published observations of accelerated ageing of the immune system as determined by the failure to restore thymic mass of the old animal and an increase of CD44 1 memory T cells in the young animal and diminished T cell proliferation and T cell receptor (TCR) signalling upon invitro stimulation [18,19]. These studies did not use congenic markers to distinguish between adult and old T cells in critical experiments, and conducted bulk T cell assays that do not account for the different proportions of T cell subsets with age.…”

Splenic Niche Cells from Young Heterochronic Parabionts Have Decreased Capability to Amplify T-cell Proliferation in Vitro

“…Earlier we investigated mechanisms of changes in the Tcell lymphoid compartment in young heterochronic partners Proliferation in Vitro during parabiosis [8]. We found that age-dependent changes in functions of the young immune system start with a disorder of the T-lymphocyte subpopulation in the spleen.…”

“…For parabiosis, animals (females) were typically joined at 2-3 (young) and 22-23 (old) months of age. A parabiosis surgery was performed exactly as described previously [8] and in accordance with the guidelines of the Administrative Panel for Lab Animal Care of the Institute. Six weeks after the initiation of parabiosis, mice were euthanized and subjected to a tissue analysis.…”

“…The total population of enriched splenic macrophages was harvested from the splenocytes by adhesion to plastic according to the routine method [8] with a few modifications. Splenocytes were obtained immediately after the disaggregating of the spleens in the complete RPMI-1640 medium.…”