3 ms·

Long telomeres do not lead to long life. Telomere length has an optional length that's not too short nor too long. Maybe activating TERT in elderly people won't

Long telomeres do not lead to long life. Telomere length has an optional length that's not too short nor too long. Maybe activating TERT in elderly people won't hurt because they won't have time to develop cancer? But it seems like a bad idea based on our tendency to project absolutes: telomeres shorten with age, so obviously we should lengthen them to be young! Right? Recent research has challenged the notion that longer telomeres are universally beneficial, revealing a complex relationship between telomere length and cancer risk. Having excessively long telomeres is indeed related to an increased cancer risk, primarily because it prevents the natural selection against potentially cancerous cells[1][3]. Key findings from recent studies include: 1. People with mutations leading to abnormally long telomeres have a higher risk of developing various cancers, including melanoma, thyroid neoplasms, and blood-related cancers[1]. 2. Long telomeres allow cells to accumulate more mutations over time, as they can divide more times before reaching critical telomere shortening[1][3]. 3. The telomere tumor suppressor pathway, which normally helps prevent cancer by limiting cell division, is less effective when telomeres are too long[4]. 4. Families with mutations in the TINF2 gene, which regulates telomere length, show a higher incidence of various cancers, including breast, colorectal, and thyroid cancers[4]. 5. Genome-wide association studies have identified both rare and common genetic variants that lengthen telomeres and are strongly associated with increased cancer risk[3]. These findings suggest that while short telomeres can lead to premature aging and organ failure, excessively long telomeres may provide a permissive environment for cancer development by allowing cells to proliferate beyond normal limits[1][3][4]. [1] Long telomeres may heighten cancer risks https://www.nih.gov/news-events/nih-research-matters/long-telomeres-may-heighten-cancer-risks https://www.nih.gov/news-events/nih-research-matters/long-te... [2] Link Between Long Telomeres and Long Life Is a Tall Tale, Study ... https://www.nytimes.com/2023/05/04/health/long-telomeres-age-longevity.html https://www.nytimes.com/2023/05/04/health/long-telomeres-age... [3] Long telomeres and cancer risk: the price of cellular immortality - PMC https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715353/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6715353/ [4] Telomere shortening protects against cancer https://www.rockefeller.edu/news/29625-telomere-shortening-protects-cancer/ https://www.rockefeller.edu/news/29625-telomere-shortening-p... [5] Mice with hyper-long telomeres show less metabolic aging ... - Nature https://www.nature.com/articles/s41467-019-12664-x https://www.nature.com/articles/s41467-019-12664-x

AstralStorm 2y ago
There's a difference between activating TERT once in a while and having it extra active all the time. I assume that before applying the drug you'd check the mean telomere length, which is easy enough to do. You probably wouldn't give it to people with actual active cancers either, and check for anything unusual afterwards, to handle with properly targeted poison. (AKA chemotherapy, and resulting cancers would be super early stage so easy to quash)
- inciampati 2y ago
  The trick is, you want the telomeres to shorten all the way in cells that rapidly divide because this ends cell lines. And if you don't end proliferating cell lines, you get cancer. All of us and all of our tissues have cells that are basically pre-cancerous, they have driver mutations associated with cancer, and the only thing preventing them from running amok is the fact that there are limitations in the number of divisions that are possible. This is all based on information that's become visible via single-spell spatial transcriptomics. See Peter Campbell's work.

AstralStorm 2y ago

There's a difference between activating TERT once in a while and having it extra active all the time. I assume that before applying the drug you'd check the mean telomere length, which is easy enough to do. You probably wouldn't give it to people with actual active cancers either, and check for anything unusual afterwards, to handle with properly targeted poison. (AKA chemotherapy, and resulting cancers would be super early stage so easy to quash)

inciampati 2y ago
The trick is, you want the telomeres to shorten all the way in cells that rapidly divide because this ends cell lines. And if you don't end proliferating cell lines, you get cancer. All of us and all of our tissues have cells that are basically pre-cancerous, they have driver mutations associated with cancer, and the only thing preventing them from running amok is the fact that there are limitations in the number of divisions that are possible. This is all based on information that's become visible via single-spell spatial transcriptomics. See Peter Campbell's work.