Telomeres

percyval577

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Because
  • there is an effect of Vitamin D on telomeres
  • EBV, CMV and one Enterovirus have been shown to block vitamin D receptor (VDR)
  • HCV is associated with Vitamin D, Parvovirus B19 can well be associated
  • HHV-6 is not associated with Vitamin but is known to affect telomeres (thread and lit. to all of these)
telomeres should be interesting.
_____________​


Questioning causal involvement of telomeres in aging
Mirre J.P. Simons 2015


Abstract (my paragraphing)
Multiple studies have demonstrated that telomere length predicts mortality and that telomeres shorten with age. Although rarely acknowledged these associations do not dictate causality.

I review telomerase knockout and overexpression studies and find little support that telomeres cause aging. In addition, the causality hypothesis assumes that there is a critical telomere length at which senescence is induced. This generates the prediction that variance in telomere length decreases with age.

In contrast, using meta-analysis of human data, I find no such decline. Inferring the causal involvement of telomeres in aging from current knowledge is therefore speculative and could hinder scientific progress.
2.2.3. from the Results
For the meta-analysis, I collected data on standard deviation from a large meta-analysis on sex differences in telomere length in the general population (Gardner et al., 2014) and I enriched this set with data from two other recent meta-analyses (Boonekamp et al., 2013, Müezzinler et al., 2013). I selected samples from which the age at sampling was on average over 45 years, after which age-related mortality occurs. Moreover, I restricted the data to include only studies that used terminal restriction fragment (TRF) analysis (southern blotting) (Kimura et al., 2010). TRF analysis is the only method in which the means and standard deviations can be reliably compared between laboratories, because it uses a single standard across laboratories (a DNA molecular weight ladder) to calculate the mean telomere length per individual (Verhulst et al., 2015). However when I analysed the available data on qPCR, the other main method used to measure telomere length, the conclusions below did not change.
[original paragraph]​

Data were analysed using the natural logarithm of the reported standard deviation of telomere length, for which the sampling variance is known to be a function of sample size (Nakagawa et al., 2014), in a mixed model setting (with study included as random term) using the R package metafor (Viechtbauer, 2010). Separate models were fitted that also included covariates such as sex, the natural logarithm of mean telomere length (Nakagawa et al., 2014), the standard deviation of subject age in the study, and any combination of these. In none of these models did variance significantly decrease with age and, in general, the estimated slope was positive rather than negative (slope of age without any covariates: 0.0015 ± 0.0036 (s.e.), p = 0.68).

The predicted reductions in the variance of telomere length are, however, not linear but depend on the increase in mortality with age (Fig. 2). The quadratic term for age, however, was also close to zero and far from significant (−0.0001 ± 0.0003, p = 0.69). Because there were no studies with mean ages between 59 and 71 years, the data could also be objectively dichotomised between young (<60 years) and old (>70 years). These two categories did not differ in telomere variance (difference 0.055 ± 0.095, p = 0.56), corroborating earlier analyses.

These results, and earlier epidemiological evidence (Boonekamp et al., 2013), therefore suggest that telomere length is not a determinant of aging but rather a marker able to explain life expectancy and disease risk, for currently unknown mechanistic reasons.
open acces
Aging Research Reviews
 
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percyval577

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Inflammation, But Not Telomere Length, Predicts Ageing at Extreme Old Age: A Longitudinal Study of Semi-supercenitenarians.
Arai et al 2015


from the Discussion, Re: Inflammation
They emphasize the apparent paradox, recognized earlier (Salvioli et al., 2013), that on one hand systemic inflammation is associated with accelerated ageing and enhanced mortality risk, while on the other hand centenarians, who have escaped those risks for longer and age slower than the general population, show high levels of systemic inflammation markers.
....
Our data suggest another interpretation: Seeing low levels of systemic inflammation in centenarian offspring indicated that the rise of inflammatory mediators in centenarians may be a relatively late, ‘catch-up’ event. Thus, future centenarians may be risk-protected over most of their lifespan by low levels of systemic inflammation, but when these levels rise towards the end of their lifespan they predict centenarian mortality, disability and cognitive decline at least as strongly as in the general population.
...
We conclude that while our multimorbidity measure might be as robust as possible in the extreme old, it still indicates that multimorbidity in our populations is not governed by inflammation and does not co-vary with either survival time, capability or cognitive function. Whether this is because of the extreme age or some other property of our study population can only be assessed by comparison to independent cohorts.
from the Discussion, Re: Telomere Length
Cross-sectionally, our data show superior maintenance of telomere length in centenarian offspring, centenarians and (semi-)supercentenarians. They confirm the finding of improved telomere length maintenance in Ashkenazy centenarians (Atzmon et al., 2010) in a genetically independent, large cohort.

They raise doubt about the validity of previous claims suggesting equal telomere shortening in centenarians (Kimura et al., 2007) or a fast drop of telomere length between centenarians and semi-supercentenarians (Tedone et al., 2014) that were derived from very low numbers of participants.

Together, our data suggest that long telomeres might be a prerequisite for exceptional lifespan in humans. They also suggest that centenarian offspring is able to counteract telomere shortening that occurs in the general population and this might contribute to their higher probability of longevity. It is possible that people with exceptional longevity, who also maintain very low risks of CVD, diabetes, and auto-immune diseases, escape from telomere-driven pathologies by maintaining relatively long telomeres.

[original paragraph]​

Given that inflammation and telomere-dependent cell senescence can drive each other thus causing accelerated ageing (Jurk et al., 2014, Tchkonia et al., 2013), we were surprised to find evidence for inflammation as driver of ageing up to (semi-)supercentenarians, while telomere length/cell senescence was no longer predictive for successful ageing once longevity had been achieved.

In a previous study comprising only 38 participants, longer telomeres were associated with better health and independence in centenarians (Terry et al., 2008). However, other studies had shown before that telomere length loses its predictive power as a biomarker of mortality and morbidity risk at ages above 75 years (Cawthon et al., 2003, Martin-Ruiz et al., 2005).

In addition, telomere length is limited as a biomarker of senescence because telomere dysfunction can induce senescence without concomitant telomere shortening (Jurk et al., 2014, Hewitt et al., 2012).
open access
EBio Medicine
 

Hip

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Telomeres are of interest to the anti-aging community, but I am not aware of any relevance to ME/CFS.
 

Sidny

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Telomeres are of interest to the anti-aging community, but I am not aware of any relevance to ME/CFS.
If one considers pathogens like EBV,CMV enteroviruses etc. as being able to screw with the vitamin D receptor and as drivers of certain chronic inflammatory diseases (ie ME/CFS) with those chronic diseases as contributing to and accelerating aging (telomere shortening) they just might be relevant in ME/CFS.
 

Hip

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@Sidny, I don't think ME/CFS patients suffer from accelerated aging. In fact I've heard it said that ME/CFS patients often look younger than their age (perhaps because being often housebound, they are not exposed to the stresses and wear and tear of working life, partying and drinking alcohol).
 

Sidny

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@Hip that’s intresting. I was under the impression that ME/CFS patients have an elevated risk of developing age related diseases such as cancer and heart disease but I suppose the limited life participation like you mentioned could slow some aspects of aging.
 

Sidny

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For example, losing subcutaneous fat in my hands and feet, face (overnight essentially) and developing thinner less collagen dense skin is a pretty overt sign of aging I would imagine. These were symptoms that developed in me (at not even 30yrs old) shortly after falling ill despite being mostly housebound. Not to mention significant loss of cognitive function (also associated with aging)
 

Hip

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@Sidny, yes the brain fog appears like age-related cognitive decline. Though we know from ME/CFS patients who have gone into remission that this brain fog clears up, so is not permanent physical damage. I bet the skin wrinkling would also clear up if you could magically remove the virus that I suspect induces connective tissue-degrading enzymes which strip elastin from the skin.