On Telomere Length and Cancer Risk
Here is an interesting study on the association of average telomere length with cancer risk, a relationship that is apparently quite hard to pull from raw epidemiological data:
Telomere shortening is an inevitable, age-related process, but it can also be exacerbated by lifestyle factors such as obesity and smoking. Thus, some previous studies have found an association between short telomeres and high mortality, including cancer mortality, while others have not. A possible explanation for the conflicting evidence may be that the association found between short telomeres and increased cancer mortality was correlational but other factors (age and lifestyle), not adjusted for in previous studies, were the real causes. Genetic variation in several genes associated with telomere length (TERC, TERT, OBFC1) is independent of age and lifestyle. Thus, a genetic analysis called a Mendelian randomization could eliminate some of the confounding and allow the presumably causal association of telomere length and cancer mortality to be studied.Researchers used data from two prospective cohort studies, the Copenhagen City Heart Study and the Copenhagen General Population Study, including 64,637 individuals followed from 1991-2011. Participants completed a questionnaire and had a physical examination and blood drawn for biochemistry, genotyping, and telomere length assays. For each subject, the authors had information on physical characteristics such as body mass index, blood pressure, and cholesterol measurements, as well as smoking status, alcohol consumption, physical activity, and socioeconomic variables. In addition to the measure of telomere length for each subject, three single nucleotide polymorphisms of TERC, TERT, and OBFC1 were used to construct a score for the presence of telomere shortening alleles.
A total of 7607 individuals died during the study, 2420 of cancer. Overall, as expected, decreasing telomere length as measured in leukocytes was associated with age and other variables such as BMI and smoking and with death from all causes, including cancer. Surprisingly, and in contrast, a higher genetic score for telomere shortening was associated specifically with decreased cancer mortality, but not with any other causes of death, suggesting that the slightly shorter telomeres in the cancer patients with the higher genetic score for telomere shortening might be beneficial because the uncontrolled cancer cell replication that leads to tumor progression and death is reduced.
Link: http://www.sciencedaily.com/releases/2015/04/150410165312.htm
Yet young humans, with longer telomeres, have a low incidence of cancer.
That was commented a lot before: a young person has long telomeres, yet low rates of cancers, but when the person gets older and telomeres shortens cancer incidence increases. Seems like certain types of cancers hijack the process and use one of the weakest links (short telomeres). I think there is a lot to look at here, both ways ... and find out very interesting things that can smooth the learning of (reverse) aging process.
The correlation of cancer with age is driven by DNA damage, inflammation, high levels of cellular senescence, and failing immune surveillance. What this paper is showing, I think, is that the slowdown in stem cell activity with age is having the expected effect of reducing cancer incidence. That correlates with telomere length because less stem cell activity means fewer new long-telomere replacement cells, which means shorter telomeres on average in any given tissue.
So more to do with Stem cells slowing down and not working as efficiently due to their Niche phenotype aging? Less new cells to replace their daughter cells makes for shorter telomeres. That makes sense as Telomeres tend to get lengthened based on the shortest one. Also explains somewhat why we see rejuvenation from blood factors which encourage Stem cells to get back to work and thus are restocking the daughter cell population again. This would also mean telomerase would be encouraged in the shortest ones giving time for them to repair themselves too.
I will also add that rejuvenated stem cells using youthful factors appeared to show DNA repair too as new daughter cells were undamaged after aged stem cells were "awakened" again. Wagers papers indicate this to be the case it appears old stem cells can work just fine if stimulated.
I take a product called TA-65 which purports to slow the shortening of telomere length -- and also, in some cases, lengthens them. Assuming that it even has the potential to do either, is this risky in light of some of the conflicting evidence regarding telomere length and cancer?
@Ann Cappola: No-one knows. TA-65 is basically junk - repackaged plant extracts and a lot of marketing.
https://www.fightaging.org/archives/2007/04/the-antiaging-marketplace-at-its-terrible-best.php
But if there was a way to meaningfully lengthen telomeres in tissues in isolation of other processes that impact health, the picture is very unclear as to what would happen to your risk of cancer. Current understanding of cell biology, in absence of specific evidence, suggests an increased cancer risk. The study linked in this post suggests a small increased cancer risk. Mouse studies with increased telomerase activity to lengthen telomeres show a reduced cancer risk, but mice have quite different telomere dynamics from humans. So it's all up in the air.
Reason: Thank you very much for your prompt reply. Well, one thing that isn't 'up in the air' is that I will be saving considerable money by opting not to take TA-65 any longer. It is a relatively expensive product and the money can be better spent on high-quality fish oils, ubiquinone, etc. Thanks again.
There are atudies that suggest it increases cancer and studies that it does not. Work by Blasco et al is the most convincing argument IMO for trying to induce Telomerase as a therapy as well as the recent work by Dr Blau both using transient AAV gene therapy.
Telomere length controls gene expression via the TPE (telomere positioning effect - Shay et al) which in turn contributes to the local environment and aged phenotype. I maintain that Telomere length is not a mitotic clock so much as its main function is regulatinig gene expression. The shorter they get the more expressed genes are changed and the epigenetic state of the cell shifts and Methylation and Histone codes change further chaning gene expression to an aged phenotype. ROS is a key factor in telomere attrition so it makes sense to try to mitigate this damage before it leads to further changes in gene expresison.
What will it do in Humans? Well we know it induces increased cell activity, repairs DNA damage and even helps mitochondria in Vitro. We will not know what it does in-vivo unless someone tries it. I know of at least three biotechs moving towards testing in the Human model, then we will know if it rejuvenates like it does in animal models.
TA-65 like other "supplements" are a waste of time, the only way to rejuvenate is via direct interventions. Supplements generally get abosrbed by the Liver/Stomach and do nothing to the wider system so they should be filed under "Snake oil" IMO.
IMO, if you stop consuming cancer feeding items, the risk should drop substantially.