Age-associated telomere attrition of lymphocytesin vivois co-ordinated with changes in telomerase activity, composition of lymphocyte subsets and health conditions

Abstract

Telomeres are essential in maintaining chromosome integrity and in controlling cellular replication. Attrition of telomere length in peripheral blood mononuclear cells (PBMCs) with age is well documented from cross-sectional studies. But the actual in vivo changes in telomere lengths and its relationship with the contributing factors within the individuals with age have not been fully addressed. In the present paper, we report a longitudinal analysis of telomere length in the PBMCs, lymphocytes and monocytes of 216 human subjects aged from 20–90 years assessed at 0-, 5- and 12-year follow-up. For the 5- and 12-year follow-up, telomere length in the PBMCs decreased in 34 % and 46 %, exhibited no detectable change in 56 % and 47 % and increased in 10 % and 7 % of the subjects respectively. The rate of telomere change was distinct for T-cells, B-cells and monocytes for any given subject. Telomerase activity declined with age in the resting T-cells and B-cells and the activated T-cells. Finally, a significant portion of telomere attrition in T-cells with age was explained by a decline in the telomerase activity, decreased naïve cells and the change in physiological conditions such as elevated blood glucose and interleukin (IL)-6 levels. These findings show that changes in the telomere length of the PBMCs with age in vivo occur at different rates in different individuals and cell types and reveal that changes in the telomere length in the T-cells with age is influenced by the telomerase activity, naïve T-cell percentage and changes in health conditions.

Discarded Human Thymus Is a Novel Source of Stable and Long-Lived Therapeutic Regulatory T Cells

“…Consistent with their origin from infant thymus, thymic Tregs have significantly longer telomere length than adult blood Tregs. Telomere shortening is one of the molecular hallmarks of aging (50)(51)(52). Vukmanovic-Stejic et al showed that rapid peripheral turnover is responsible for the maintenance of human Tregs during aging and is associated with critically short telomeres, low telomerase activity, and higher susceptibility to apoptosis (38).…”

Crack cocaine addiction, early life stress and accelerated cellular aging among women

“…Our study also did not measure telomerase activity, which could have an impact on the current findings. It is known that telomerase influences the rate of change in TL of peripheral blood mononuclear cells (Lin et al, 2015).Additionally, the cross-sectional design does not allow assessment of within-individual changes in TL over the lifespan. This approach is only able to estimate how the cellular aging processes may proceed based on measurement of individuals with a range of ages and exposures.…”

Safety and Efficacy of Biological Disease-Modifying Antirheumatic Drugs in Older Rheumatoid Arthritis Patients: Staying the Distance

“…Changes observed in the immune system of RA patients are similar to those in the elderly, leading ultimately to breach of self-tolerance. Just like in older individuals, telomere shortening in the lymphocytes [19], T-cell aging and emergence of CD28-cells are seen in RA patients [13]. But whether these changes suggesting immunosenescence are a cause or a consequence of RA is still unclear.…”

“…Similarly in this cohort, adverse events were not different between age groups. 19 Long-term analyses of the clinical trials and within real-life cohorts indicate that the withdrawal rate for this drug is relative low e.g just over 30% after two years in a large reallife cohort [89] and mainly occurring during the first two courses in around one-third of patients, irrespective of age (even in the very elderly, ≥ 75 years) [91]. Comparisons of drug survival among different biological agents is not easy as the administration interval may play a role in the patient's or physician's decision to stop a given treatment, but also in the recording and analysis of drug survival data.…”