Background Ageing is a complex phenomenon that leads to decreased proliferative activity, loss of function of the cells, and cellular senescence. Senescence of the immune system exacerbates individual’s immune response, both humoral and cellular but increases the frequency of infections. We hypothesized that physiological ageing of adaptive immune system occurs in recipients of allogeneic hematopoietic cells transplant (allo-HCT) at faster rate when compared to their respective donors since the small number of donor cells undergo immense proliferative stress restoring recipients hematopoiesis. We compared molecular characterizations of ageing between recipients and donors of allo-HCT: telomeric length and immunophenotypic changes in main lymphocyte subsets – CD4+, CD8+, CD19+, CD56+. Results Median telomeric length (TL) of CD8+ lymphocytes was significantly longer in donors compared to recipients (on average 2,1 kb and 1,7 kb respectively, p = 0,02). Similar trends were observed for CD4+ and CD19+ although the results did not reach statistical significance. We have also found trends in the immunophenotype between recipients and donors in the subpopulations of CD4+ (naïve and effector memory), CD8+ Eomes+ and B-lymphocytes (B1 and B2). Lower infection risk recipients had also a significantly greater percentage of NK cells (22,3%) than high-risk patients (9,3%) p = 0,04. Conclusion Our data do not support the initial hypothesis of accelerated aging in the long term all-HCT recipients with the exception of the recipients lymphocytes (mainly CD8+) which present some molecular features, characteristic for physiological ageing (telomeric shortening, immunophenotype) when compared to their respective donors. However, a history of lower infection numbers in HCT recipients seems to be associated with increased percentage of NK cells. The history of GVHD seems not to affect the rate of ageing. Therefore, it is safe to conclude that the observed subtle differences between recipients’ and donors’ cells result mainly from the proliferative stress in the early period after allo-HCT and the difference between hosts’ and recipients’ microenvironments.

It has been hypothesized that α-Klotho deficiency might contribute to chronic inflammation in patients with end-stage renal disease (ESRD), especially those on hemodialysis (HD). Serum Klotho levels by some authors are considered a potential predictor of cerebrovascular events. Therefore, we analyzed serum levels of α-Klotho with ELISA and inflammation-related cytokines in HD patients. Sixty-seven HD patients and 19 healthy people were recruited between November 2017 and June 2021. A Cytometric Bead Array (CBA) was used to determine the level of different cytokines: IL-12p70, TNF, IL-10, IL-6, IL-1β, and IL-8. A human Klotho ELISA kit was used to determine the level of α-Klotho in the plasma samples of HD patients. There was no difference in serum levels of α-Klotho between HD patients and healthy people. Patients had increased serum IL-6 and IL-8. Significant positive correlations existed between the concentration of α-Klotho and the serum concentrations of IL-12p70, IL-10, and IL-1β. However, in a multivariable linear regression analysis, only patients’ age was associated independently with α-Klotho level. Serum α-Klotho was not associated with higher mortality risk in HD patients. While these results draw attention to potential relationships between α-Klotho proteins and inflammatory markers in HD patients, our cross-sectional study could not confirm the pathogenic link between α-Klotho, inflammation, and cardiovascular mortality.

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Background: Ageing is a complex phenomenon that leads to decreased proliferative activity, loss of function of the cells, and cellular senescence. Senescence of the immune system exacerbates individual’s immune response, both humoral and cellular but increases the frequency of infections. We hypothesized that physiological ageing of adaptive immune system occurs in recipients of allogeneic hematopoietic cells transplant (allo-HCT) at faster rate when compared to their respective donors since the small number of donor cells undergo immense proliferative stress restoring recipients hematopoiesis. We compared molecular characterizations of ageing between recipients and donors of allo-HCT: telomeric length, proinflammatory cytokines concentration, and immunophenotypic changes in main lymphocyte subsets – CD4+, CD8+, CD19+, CD56+.Results: Median telomeric length (TL) of CD8+ lymphocytes was significantly longer in donors compared to recipients (on average 2,1kb and 1,7kb respectively, p = 0,02). Similar trends were observed for CD4+ and CD19+ although the results did not reach statistical significance. We have also found trends in the immunophenotype between recipients and donors in the subpopulations of CD4+ (naïve and effector memory), CD8+ Eomes+ and B-lymphocytes (B1 and B2). When grouped according to the history of infections, there were differences between recipients in the TNF-a and Il-4 concentrations. They were higher in the recipients with lower infection number p=0,05 and p=0,003 respectively. Lower infection risk recipients had also significantly greater percentage of NK cells (22,3%) than high-risk patients (9,3%) p=0,04.Conclusions: Our results support the hypothesis of accelerated ageing of the recipients lymphocytes observed mainly in CD8 subset compared to their respective donors. Quantitative changes in recipients immunophenotype in some lymphocyte subsets resemble physiological ageing-associated changes. No difference in cytokine concentrations suggests that inflammageing does not increase in allo-HCT recipients, however a lower infection numbers in HCT recipients seems to be associated with increased concentration of proinflammatory cytokines and increased percentage of NK cells. The GVHD does not affect the rate of ageing. Therefore, the differences between recipients and donors cells may result from the proliferative stress in the early period after allo-HCT and the difference between hosts and recipients microenvironments, the only other variable that may influence the identical cells originating from donor hematopoiesis.

We investigated the relationship between α-Klotho and cytokines related to inflammation in HD patients. We analyzed levels of α-Klotho with ELISA and inflammatory cytokines with CBA in the serum of HD patients. There was a significant negative correlation between the concentration of serum α-Klotho and patients’ age and the serum concentration of PTH. No correlation has been found between α-Klotho and Ca or Pi. HD time, creatynine or eGFR. However, there were significant positive correlations between the concentration of α-Klotho and the serum concentration of IL-12p70, IL-10, and IL-1β. Furthermore, the concentration of IL-10 and IL-1β was significantly lower in HD patients with low α-Klotho concentrations compared with HD patients with high α-Klotho. However, in a multivariable linear regression analysis, only patients’ age was associated independently with α-Klotho level. While these results draw our attention to potential relationships between α-Klotho proteins and inflammatory markers in HD patients, our cross-sectional study could not fully explain the pathogenic link between α-Klotho and inflammation in these patients. Therefore, further studies are necessary to clarify these relationships. However, this observation aligns with previous studies that confirm a significant relationship between Klotho concentration and human aging.