Why You Don't Want Long Telomeres

[haidut]

The dietary supplement industry is currently going nuts over supplements that increase telomere length or at least slow down their shortening as a way to prevent aging. As Ray has written many times, this is a highly dangerous and wrong approach as long telomeres increase risk of cancer. Telomere elongation is activated by stress, estroge, cortisol, prolactin, etc. Considering this, the study below is not a surprise but it is good to have some independent verification that messing with telomere length is misguided and dangerous. Also, I don't but the lack of connection between longer telomeres and cancers other than of the lung. I think it is a matter of time before that connection is discovered.

http://hmg.oxfordjournals.org/content/e ... dv252.full
http://sciencelife.uchospitals.edu/2015 ... ncer-risk/

"...In a paper published in Human Molecular Genetics on July 29, Pierce and his colleagues describe the results from their study – an unexpected link between long telomeres and an increased risk of lung adenocarcinoma. Surprisingly, no significant associations between telomere length and other cancer types or subtypes were observed."

 

[Mauritio]

Couldn't it be that the telomeres elongate as a defensive mechanism to the increase in stress hormones, because the body senses an a thread that will certainly shorten life span (stress hormones) and tries to counteract that by increasing telomere length to elongate life time.

Its the same as high cholesterol and heart disease .
And just because there's firemen near every fire ,doesn't mean they caused the fire.

The authors put it that way :
"However, caution regarding this causal interpretation is warranted in light of the potential issue of pleiotropy, and a more general interpretation is that SNPs influencing telomere biology are also implicated in lung adenocarcinoma risk"

 

[Mauritio]

Actually I think the most plausible explanation would be the following

"A protective effect of short TL on lung cancer risk has a biologically plausible explanation, as short telomeres could protect against cancer by triggering cell senescence or programmed cell death in the presence of functional cell cycle checkpoints and intact apoptotic pathways (44)"

It is known that cellular senesence is a double edged sword . But I highly doubt that having many senescent cells is healthy as it has it's own inflammatory secretome and inflammation is associated with heart disease ,alzheimers and stroke ,...
So by having longer telomeres you have less senescent cells and thus possibly higher cancer risk but lower risk in diseases that are associated with inflammation:

• cancer. (LOL)
• heart disease.
• rheumatoid arthritis.
• type 2 diabetes.
• obesity.
• asthma.
• neurodegenerative diseases, such as Alzheimer's disease.

Also smoking cigarettes is associated with short telomeres and lung carcinoma

So I guess it might be smart to keep telomeres long ,senescent cells short to live a long life . What might make it even longer is to take a bit of aspirin and vitamin k to prevent possible higher cancer risk.

 

[Mauritio]

Also there's this interesting study. It's only done in mice but o think its results are Interesting and the authors of the article/ the study have some peaty things to say that they observed :

Scientists Dramatically Extend The Lifespans of Mice in a Genius New Telomere Study
This finding supports the idea that, when it comes to determining longevity, genes are not the only thing to consider," says molecular biologist Maria Blasco, from the Spanish National Cancer Research Centre (CNIO). "There is margin for extending life without altering the genes.
The experiment worked: the long telomere mice lived an average of 24 percent longer, were slimmer, and less likely to develop cancer. Various indicators of metabolic ageing turned out to be lower too, the researchers report.


The experiment worked: the long telomere mice lived an average of 24 percent longer, were slimmer, and less likely to develop cancer. Various indicators of metabolic ageing turned out to be lower too, the researchers report.

These mice had less 'bad' cholesterol in their bodies, and their DNA wasn't damaged as much as the animals got older. What's more, their mitochondria functioned better as well.

 

[MetabolicTrash]

Doesn't this counter the idea that stress is entirely bad somewhat?

If stress can lengthen telomeres -- and longer telomeres may be adjusted to try and augment lifespan as a natural consequence -- then longer telomeres may be adapted to counteract the hormones, which could mean that stress itself might somewhat increase lifespan through natural and adaptive measures of trying to deal with it. In this case one could argue that -- if longer telomeres are adjusted in the midst of stress to adapt -- then long telomeres may not be wholly bad if by adapting in the first place they are making certain conditions more favorable in some way, even though not the most ideal one.

I know some here really don't like the non-Peaty views on age reduction theories or applications in medical science, but I always prefer to give the benefit of the doubt with most research/anti-aging science and foundations, especially if more independent.

 

[Mauritio]

Doesn't this counter the idea that stress is entirely bad somewhat?

If stress can lengthen telomeres -- and longer telomeres may be adjusted to try and augment lifespan as a natural consequence -- then longer telomeres may be adapted to counteract the hormones, which could mean that stress itself might somewhat increase lifespan through natural and adaptive measures of trying to deal with it. In this case one could argue that -- if longer telomeres are adjusted in the midst of stress to adapt -- then long telomeres may not be wholly bad if by adapting in the first place they are making certain conditions more favorable in some way, even though not the most ideal one.

I know some here really don't like the non-Peaty views on age reduction theories or applications in medical science, but I always prefer to give the benefit of the doubt with most research/anti-aging science and foundations, especially if more independent.

I guess that amount is probably minimal . I suspect that up until a certain point you're right, if the elongation of telomeres is indeed an adaption to stress, but I suspect that the elongation reaches a plateau at some point even if the stress increases meaning there is a sweet spot for minimal stress and maximal telomere elongation . I also suspect that most people have way more stress than would be optimal for this.
This whole scenario would be similar to the "toughening up" response of the organism that follows a minimal endotoxin exposure
,that peat described as beneficial.

 

[Mauritio]

Also if you want short telomeres than somebody has to explain to me why PUFA shortens telomeres: So we should all consume our daily PUFA to stay young ? ...dont think so. I still think its great to avoid PUFA ,but also that long telomeres are better than short ones.

"...PUFA and fish oil effectively inactivated testicular telomerase"
Polyunsaturated fatty acids ameliorate aging via redox-telomere-antioncogene axis

 

[Mito]

Mice with hyper-long telomeres show less metabolic aging and longer lifespans

• Published: 17 October 2019

Nature Communications volume 10, Article number: 4723 (2019) | Download Citation
Abstract
Short telomeres trigger age-related pathologies and shorter lifespans in mice and humans. In the past, we generated mouse embryonic (ES) cells with longer telomeres than normal (hyper-long telomeres) in the absence of genetic manipulations, which contributed to all mouse tissues. To address whether hyper-long telomeres have deleterious effects, we generated mice in which 100% of their cells are derived from hyper-long telomere ES cells. We observe that these mice have longer telomeres and less DNA damage with aging. Hyper-long telomere mice are lean and show low cholesterol and LDL levels, as well as improved glucose and insulin tolerance. Hyper-long telomere mice also have less incidence of cancer and an increased longevity. These findings demonstrate that longer telomeres than normal in a given species are not deleterious but instead, show beneficial effects.
https://www.nature.com/articles/s41467-019-12664-x
Mice with hyper-long telomeres show less metabolic aging and longer lifespans

 

[Mauritio]

Very interesting, that's the same study that the article quoted above mentioned...
Lean and low cholesterol = high metabolism
Also very interesting that they had lower incidence of cancer ,given the fact that some say that longer telomeres / less senescent cells means higher cancer risk overall!
I am going to give the full text a read.

An older study came to the same conclusion: namely no increased cancer and a quarter more life time .
https://www.embopress.org/doi/full/10.1002/emmm.201200245
"A major goal in aging research is to improve health during aging. In the case of mice, genetic manipulations that shorten or lengthen telomeres result, respectively, in decreased or increased longevity. Based on this, we have tested the effects of a telomerase gene therapy in adult (1 year of age) and old (2 years of age) mice. Treatment of 1‐ and 2‐year old mice with an adeno associated virus (AAV) of wide tropism expressing mouse TERT had remarkable beneficial effects on health and fitness, including insulin sensitivity, osteoporosis, neuromuscular coordination and several molecular biomarkers of aging. Importantly, telomerase‐treated mice did not develop more cancer than their control littermates, suggesting that the known tumorigenic activity of telomerase is severely decreased when expressed in adult or old organisms using AAV vectors. Finally, telomerase‐treated mice, both at 1‐year and at 2‐year of age, had an increase in median lifespan of 24 and 13%, respectively. These beneficial effects were not observed with a catalytically inactive TERT, demonstrating that they require telomerase activity. Together, these results constitute a proof‐of‐principle of a role of TERT in delaying physiological aging and extending longevity in normal mice through a telomerase‐based treatment, and demonstrate the feasibility of anti‐aging gene therapy.