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High Functioning Centenarians Have Longer Telomeres, More Telomerase Activity, and Better Measures of Immune Function


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Posted 06 December 2018 - 09:23 PM


Today I'll point out an open access paper in which the authors divide centenarians into two groups based on the degree of age-related dysfunction. They find that centenarians with comparatively lower levels of dysfunction also have longer telomere length and more telomerase activity in white blood cells taken from a blood sample. Further, aspects of their immune response that are not directly related to telomeres and telomerase also appear more capable.

In one sense this telomere length data is the expected result: telomere length is a measure of biological aging. When considered generally it is a measure of the burden of age-related molecular damage and consequent dysfunction, but when measured in white blood cells it is also to some degree a measure of the decline of the immune system. Less functional centenarians are clearly more physiologically aged than more functional centenarians, and therefore should exhibit shorter average telomere length.

On the other hand, telomere length in white blood cells is such a terrible measure of aging that finding no difference between the two groups would also be unsurprising. Over the years, a fair number of comparison studies have failed to find the expected differences in telomere length between study populations of differing health status. Telomere length as it is presently measured only reliably shows correlations with aging over very large study populations, averaging out the large short-term fluctuations resulting from health and environmental changes, and is certainly not much use as a marker for individual decision making in health matters.

Thus I would say that the more important data here is that directly relating to the immune response, rather than the telomere length results. The immune system is critical not just in defense against pathogens, but also in destroying errant and potentially harmful cells, as well as playing an important role in regeneration and tissue maintenance. When the immune system falters with age, declining into chronic inflammation and incapacity, a great many other functions decline with it.

Telomere length and telomerase activity in T cells are biomarkers of high-performing centenarians

It is generally recognized that the function of the immune system declines with increased age and one of the major immune changes is impaired T-cell responses upon antigen presentation/stimulation. Some "high-performing" centenarians (100+ years old) are remarkably successful in escaping, or largely postponing, major age-related diseases. However, the majority of centenarians ("low-performing") have experienced these pathologies and are forced to reside in long-term nursing facilities.

Previous studies have pooled all centenarians examining heterogeneous populations of resting/unstimulated peripheral blood mononuclear cells (PBMCs). T cells represent around 60% of PBMC and are in a quiescent state when unstimulated. However, upon stimulation, T cells rapidly divide and exhibit dramatic changes in gene expression. We have compared stimulated T-cell responses and identified a set of transcripts expressed in vitro that are dramatically different in high- vs. low-performing centenarians.

We have also identified several other measurements that are different between high- and low-performing centenarians: (a) The amount of proliferation following in vitro stimulation is dramatically greater in high-performing centenarians compared to 67- to 83-year-old controls and low-performing centenarians; (b) telomere length is greater in the high-performing centenarians; and © telomerase activity following stimulation is greater in the high-performing centenarians. In addition, we have validated a number of genes whose expression is directly related to telomere length and these are potential fundamental biomarkers of aging that may influence the risk and progression of multiple aging conditions.


View the full article at FightAging
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