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Does absolute telomere length have any effect on aging?

Image credit: https://medicalxpress.com/news/2017-03-link-telomere-length-cancer.html

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Shubhankar Kulkarni
Shubhankar Kulkarni Aug 04, 2020
We know that the rate of shortening of telomeres or rather the impaired functioning of the shortened telomeres has an effect on aging and also is a predictor of aging.
However, whether the absolute telomere length has any effect on aging is debated.

Can we weigh the arguements on both the sides and come up with an acceptable model? If not, can we come up with empirical ways to solve the debate?

[1]Karlseder J. Senescence Induced by Altered Telomere State, Not Telomere Loss. Science (80- ) [Internet]. 2002 Mar 29;295(5564):2446–9. Available from: https://www.sciencemag.org/lookup/doi/10.1126/science.1069523

[2]Ain Q, Schmeer C, Penndorf D, Fischer M, Bondeva T, Förster M, et al. Cell cycle-dependent and -independent telomere shortening accompanies murine brain aging. Aging (Albany NY) [Internet]. 2018 Nov 20;10(11):3397–420. Available from: http://www.aging-us.com/article/101655/text

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Hyperactive telomerases could be one solution

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Andrew Muchlinski
Andrew Muchlinski Aug 10, 2020
I think there are a few big factors here. The first is the natural shortening of telomeres as a result of cell division over the lifespan of the organism. The second is the impairment or reduced activity of telomerases due to stress and underlying disease. Both of these can result in the eventual loss of the telomere, exposing valuable protein-coding sections of the DNA, risking DNA damage and disease onset. The data are mixed on the viability of over-expressing telomerases since in some cases we see shortened life-spans as a function of increased cancer rates. However, we do have examples from mice where life span was increased. Interestingly, a longevity study focused on longer living adults also indicated that certain groups that lived longer had hyperactive telomerase genes. Therefore, I think it is still viable to continue exploring the correlation between telomerase activity and longevity. It could be possible to determine the basis of the telomerase hyperactivity and use an accelerated breeding technique e.g. CRISPR/Cas9 to engineer this activity for increased lifespan.
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Shubhankar Kulkarni
Shubhankar Kulkarni9 months ago
Hi Andrew, thank you for suggestion. I am trying to better understand it. The diseases that arise due to shortened telomeres are known. However, whether the absolute telomere length (at birth) that may vary across the individuals in a population has any effect on aging is what I want to focus on. If one individual of a species has inherently longer telomeres, does that individual show less severe manifestations of age? Does that individual live longer as compared to others? Or the original length of telomeres does not matter and the loss (during the lifespan) of telomeres dictates the severity of the aging phenotype? Are you suggesting "hyperactive telomerases" as a solution to test these questions empirically? What hyperactive telomerases will do is alter the loss of telomeres that happens during the lifespan of the individual. This might not answer the question of absolute telomere length. What we might need is an observation experiment (for starters). We need to measure the lengths of telomeres of individuals within a population and correlate it with the lifespan of those individuals. Have such studies been reported?

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