Telomere Length: How your genes affect telomeres and aging

telomeres and aging

What are telomeres and why are they important?

Telomeres are the region of repeated nucleotides (the A, G, and T’s) that are found on the ends of all of your chromosomes.  They cap off the end of the chromosomes, protecting the nuclear DNA during replication before cell division. [ref]

Each time a cell divides, it makes a copy of the nuclear DNA and a little bit of the telomere is lost. When DNA replicates, it can’t replicate the very end part of the chromosome, where the telomere is located.

Eventually, the telomere is shortened so much that it signals to the cell to stop dividing. Not enough telomere is left to protect the end of the chromosome from being lost when replicating. This then prompts the cell to either be destroyed through apoptosis or the cell becomes senescent.

telomeres and your genes

How often do cells divide?

Cells are replicating and dividing all the time in the body. You are constantly losing skin cells and making new ones. The cells in the intestines are constantly dividing and turn over every three to five days. Other cells, like neurons in the brain, generally do not replicate very often (or at all).[ref] [ref]

Adult stem cells, also called somatic stem cells, are cells that can become different types of cells.

Take, for example, the cells in the intestines that are dividing all the time…  Eventually, the cells reach the point that they can no longer divide because the telomeres are too short. This initiates apoptosis (cell death). New cells then are created by the stems cells that line the crypts in the intestines. [ref]

Can telomeres be lengthened?

The enzyme telomerase reverse transcriptase is responsible for replenishing telomeres.  This happens regularly in stem cells (to some extent) and in cancer cells (a lot!). Telomerase is also active in lymphocytes (immune system cells) and keratinocytes (skin cells). [ref]

Telomerase adds back nucleotide repeats to the end of the chromosomes, thus replenishing and lengthening telomeres.[ref]

In regular cells in the body, telomerase is turned off. This causes the replicating cells to have a biological time clock in them — replicate enough times and then cell death occurs. Most cells divide about 50 times, which is known as the Hayflick limit.[ref]

As we age, though, the telomerase activity in stem cells decreases. Eventually, then the stem cells may become senescent.[ref]

Can telomerase be activated in regular cells to increase the length of the telomeres? Studies show that there are things we can do to increase the length of our telomeres – more on that in the Lifehacks section.

What is cellular senescence?

Cellular senescence is a state where the cell is no longer dividing but doesn’t go through apoptosis. Instead, the cell stays and actively produces cytokines. Senescence is a good thing when it comes to tumor cells because it stops the growth and triggers signals to be removed by the immune system.

Cellular senescence, though, is also thought to be one reason for the problems seen in aging.  Senescent cells give off inflammatory cytokines, increasing inflammation in that tissue or organ. These signals that the senescent cells give off can also transform neighboring cells. [ref]

Which diseases are short telomeres associated with?

Cardiovascular disease is associated with shorter telomere length, and genetic variants that cause shorter telomeres increase the risk of cardiovascular disease. [ref] This has been shown repeatedly with many studies showing an increase in heart attack and stroke risk. [ref]

More specifically, short telomeres are associated with increased atherosclerosis in the carotid artery. Definitely not a good thing. [ref]

Type 2 diabetes is also associated with shorter telomere length. For each standard deviation of decrease in telomere length, the risk of diabetes increases by 37%. [ref]

Bipolar disorder is associated with significantly shorter telomere length. [ref]

PTSD from sexual assault or childhood trauma (but not combat) is associated with shorter telomere length [ref]

Various different cancers are associated with shortened telomeres, possibly because shortened telomeres could cause more DNA instability. [ref]

To sum this up, studies show shortened telomeres associated with:

  • heart attack
  • stroke
  • atherosclerosis
  • type 2 diabetes
  • depression
  • bipolar disorder
  • cancer

The chicken and the egg question comes to mind here:
Are the above diseases causing the telomeres to shorten or are the shorter telomeres causing the disease?  The answer, I think, is that both are true. Genetic studies show that variants that cause shortened telomeres also increase the risk of the above disease. [ref] But oxidative stress due to obesity or diabetes could also cause telomeres to be shorter. [ref]

Can telomerase be increased in cells to prevent aging and neurodegeneration?

There are mouse studies showing that increasing telomerase reduces the effects of aging. Human cell studies show that modifying the mRNA for telomerase can increase telomere length. [ref][ref]

One really cool study showed that turning off the telomerase gene (TERT) caused rapid aging in mice, and then turning back on the gene reversed the aging. [ref] Another mouse study, done in mice that were bred to be cancer-resistant, found that increasing telomerase extended lifespan by 43%.[ref]

Upregulating telomerase in skin cells of mice resulted in faster wound healing, but the mice were also much more susceptible to skin cancer.[ref] Timing may matter on this, though, since old mice that had telomerase reactivate using gene therapy increased longevity (24%) and didn’t have an increase in cancer. [ref]

So, what is all this about cancer?

There are still a lot of questions to be answered in this field.

On the one hand, shorter telomeres may decrease immune function, increasing the risk of several types of cancer.[ref]

On the other hand, telomerase is greatly elevated in cancer, leading to the immortality of some cancer cells. Plus, genetically longer telomere length is associated with an increased risk of lung cancer in non-smokers (Asian, women) and with an increased risk of kidney cancer.[ref][ref]

Telomerase is reactivated (turned on) in 90% of cancer cells, leading to the hallmark of limitless growth in the cells.[ref] Mutations in the TERT (telomerase enzyme) gene are commonly found in cancer cells.  These are not inherited mutations, but mutations that happened in the cells that became cancerous. [ref]

In general, things that increase cell growth can also increase cancer cell growth. So always keep in mind that telomerase is also involved in cancer growth. When reading about ways to increase telomerase, there could be a balance between decreasing the effects of aging and promoting cancer. [ref] There is still a lot of research to be done on this topic, so a little caution is justified when trying to increase telomerase.

What else does telomerase do?

Telomerase has also been shown to be active outside of its job of increasing telomere length. Within the mitochondria, telomerase has been shown to regulate reactive oxygen species. In heart disease, telomerase activity in the mitochondria is protective against atherosclerosis. [ref]

Telomerase has also been shown to regulate gene expression, and this is an ongoing field of research. [ref]

How can you get your telomeres measured?

Telomeres, in most studies, are measured in leukocytes, which are a type of white blood cell in the immune system.

There are several telomere testing companies now in the US and Europe.  I haven’t used any of them, so I can’t comment on how valid the results are (or aren’t).

Do read the privacy policy and ask questions before submitting your sample to a company! In trying to review privacy policies, some companies just use boilerplate policies talking about cookies and never mentioning what they are doing with your data. Also – realize that some companies are signing you up for a supplement subscription along with your telomere test. Other companies may use your ‘survey’ results for research purposes. Look for accreditation and licensing for the lab, also.

Testing the length of telomeres for determining biological age is still fairly new, though. Here is an interesting article that brings up several critical points about the flaws in current direct-to-consumer telomere testing companies: Telomere Testing: Science or Snake Oil

 


Genetic Variants that impact telomere length:

Telomere length is estimated to be 34-82% heritable. This means that genetics plays a pretty big role in telomere length, but that diet and lifestyle factors are also very important. [ref]

Note that the increase in cancer risk from shorter telomeres seems to depend on the type of cancer.

TERT gene: codes for the rate-limiting subunit of the telomerase enzyme that binds with the RNA

Check your genetic data for rs10069690 (23andMe v4, v5; AncestryDNA):

  • T/T: decreased telomerase activity [ref] increased risk of uterine fibroids [ref] increased risk of breast cancer [ref] increased risk of heart disease [ref] 51% increase in risk for ovarian cancer only if using estrogen therapy [ref] increased risk of kidney cancer[ref]
  • C/T: decreased telomerase, increased risk of fibroids, breast cancer, ovarian cancer, kidney cancer, heart disease.
  • C/C: normal

Check your genetic data for rs2736100 (23andMe v4, v5; AncestryDNA):

  • C/C: increased risk of glioma, lung cancer [ref][ref]
  • A/C: most common genotype
  • A/A: decreased telomere length [ref], increased risk of testicular cancer [refincreased risk of depression [ref]

Check your genetic data for rs2853669 (23andMe v4, v5; AncestryDNA):

  • A/A: normal genotype, increased survival in cancers with TERT mutations[ref]
  • A/G: decreased survival rates in cancers that have TERT mutations
  • G/G:  decreased survival rates in cancers with TERT mutations (except glioblastomas)[ref][ref] [ref]

Check your genetic data for rs2736122  (23andMe v5 only):

  • G/G: normal
  • A/G: increased risk of heart disease and stroke in African-Americans [ref] increased risk of endometrial cancer[ref]
  • A/A: increased risk of heart disease and stroke in African-Americans [ref] increased risk of endometrial cancer[ref]

Check your genetic data for rs2242652 (23andMe v5; AncestryDNA):

  • G/G: normal
  • A/G: increased risk of breast cancer,
  • A/A: decreased telomerase expression, increased risk of ER-negative breast cancer [ref] increased risk of prostate cancer [ref]

Check your genetic data for rs2736108 (23andMe v5; Ancestry)

  • T/T: longer telomeres, decreased risk of breast cancer [ref]
  • C/T: reduced risk of breast cancer
  • C/C: normal

TERC gene: codes for the RNA component of the telomere

Check your genetic data for rs10936599 (23andMe v4, v5; AncestryDNA):

  • C/C: normal (longer telomere length [ref])
  • C/T: decrease telomere length, increased risk of depression, lung cancer
  • T/T: decreased telomere length (3.9 years)[ref][ref], increased risk of recurrent depression[ref], inc. risk of lung cancer[ref]

NAF1 gene: codes for an RNA binding protein

Check your genetic data for rs7675998 (23andMe v5 only):

  • G/G: normal
  • A/G: possibly shorter telomeres
  • A/A:  shorter telomeres[ref][ref][ref]

OBFC1 gene: codes for a component of the telomere binding complex

Check your genetic data for rs9420907 (23andMe v4, v5; AncestryDNA):

    • A/A: most common genotype
  • A/C: longer telomeres
  • C/C: longer telomeres [ref][ref]

 


Lifehacks for telomerase:

Telomerase inhibitors:

Natural inhibitors of telomerase are things we often use for health and cancer prevention. Here is a partial list[ref]:

  • I3C, a component of broccoli, inhibits telomerase and down-regulates TERT.
  • Allicin, a component of garlic, reduces TERT levels.
  • EGCG, a component of green tea, binds to TERT and inhibits it.
  • Gingerol, a component of ginger, reduces TERT activity.
  • Sulforaphane, from broccoli and cauliflower, inhibits telomerase.

Ways to increase telomerase:

Prioritize your sleep. A study found that higher quality sleep and longer sleep time is associated with longer telomere length. [ref]  Another study quantified it: each additional hour of sleep over 5 hours was associated with 27 base pair lengthening of telomeres. [ref]

Another study showed that people who stay up later and have delayed circadian rhythm also have significantly shorter telomeres.[ref] Block out blue light at night (blue-blocking glasses or just turn off electronics and overhead light).

Avoid BPA: A 2017 study shows that low levels of BPA (from plastics) inhibits telomerase activity. [ref]

TA-65, derived from Astragalus membranaceus, is a well-studied telomerase activator.[ref] The manufacturer’s study on it shows that it decreases fasting glucose, insulin, blood pressure, and homocysteine. It increased bone mineral density. [ref] It sounds great, but personally, I haven’t tried it since it retails at $600/bottle!

Astragalus is a medicinal herb that has been used for thousands of years in Traditional Chinese Medicine. It has been shown to have an overall anti-aging effect and to upregulate telomerase. [ref][ref]  You can get astragalus at your local health food store or from Amazon (and it is way less than $600/bottle).

Fiber: A study showed that increasing fiber intake is associated with longer telomeres. The study estimates that 10g increase in fiber per 1000 calories equates to a reduction in biological age of 5.4 years. [ref]

Cooked (not raw) Brassica leaves – like mustard greens – was shown in a human trial to increase telomerase activity in healthy volunteers. [ref]

Stop smoking!  A meta-analysis of 30 studies show that telomere length is shorter in people who currently smoke – and in people who had ever smoked. [ref]

Stay active.  Moderate activity level is associated with longer telomere activity in middle-aged and older people. [ref][ref] Acute exposure to long-distance (endurance) running decreases telomere length.[ref] Other studies show that marathon runners have similar telomere lengths to a healthy, sedentary control group.[ref]  The key here may be age – and staying active as you age may keep your telomeres longer. [ref] Moderate exercise may have a slight advantage over more extreme exercise, at least in the short term. Being sedentary is linked to shorter telomeres. [ref]

Omega-3’s: A study that looked at supplementing with omega-3’s (fish oil) found that instead of omega-3’s on their own increasing telomere length, it was the change in the ratio of omega-6: omega-3 that helped to increase telomere length. [ref] In other words –  decreasing the amount of omega-6 (fried foods, soybean oil, sunflower seed oil, etc) and increasing the amount of seafood with omega-3s may help.

Decrease soda: Drinking soda has been found to be associated with shorter telomeres, but drinking fruit juice was marginally associated with longer telomeres. Drinking soda daily was estimated to reduce telomere length equivalent to 1.9 years of aging. [ref]

Resveratrol has been shown to increase telomerase in heart cells and in mice. [ref]

A research peptide, epitalon, has been shown in animal studies to increase telomerase. [ref][ref] This isn’t something that is FDA approved, and most of the research is on animals (and in Russian), so I would say that caution is warranted with this one.

 

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5 Comments on “Telomere Length: How your genes affect telomeres and aging

  1. This is very interesting. Thank you for your research.

  2. Thank you for the research, it was quite enlightening.

    Still, I am a bit confused by the life hacks. You say that eating broccoli, ginger, etc. is good for health and cancer prevention, as it “inhibits telomerase”.

    However, sleeping well and other life hacks increase telomerase. My wife and I, both plant-based whole foods eaters, do all of the above.

    I find this confusing. Are you saying that the goal is to strike a good balance between inhibiting telomerase and increasing it?

  3. There is an Azorean soup recipe that I grew up drinking/eating that my mom made in winter in California that used mustard greens, garlic, Turnip and red wine vinegar that always made me feel better. Kind of like chicken soup makes you feel when you are sick. Also I did research on Astragalus mollisimus a locoweed in New Mexico and the main chemical that caused the cattle to become crazy was called Swansonine an Alkaloid. Wondering if any other Alkaloids could increase or decrease Telomerase activity. I also like garlic, ginger and broccoli together with sliced red onion.

    • The Azorean soup sounds great! I’m going to have to try that. Mustard greens are so easy to grow here.
      And thanks for mentioning the Astragalus locoweed. I just looked it up – and realized that it was blooming when we were out in New Mexico and western Colorado earlier this summer. I’ll have to dig into the research and see if other alkaloids affect telomerase.
      Thanks for leaving a comment.
      Debbie

  4. Nice article! I also read some research about melatonin, pueraria, ginkgo, taurine, beta carotene (carotenoids in general), lithium, zinc, curcumin, nitric oxide, milk thistle and many other bioactives/nutrients increasing telomerase activity.

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