Jun
17
2023

Telomeres can Protect you from Premature Aging

Longer telomeres can protect you from premature aging, and shorter telomeres lead to premature death and various diseases. But recently new research showed that sometimes longer telomeres can be responsible for cancer and lower life expectancy. I will discuss this further below.

Some facts about telomeres

Telomeres are the caps on the chromosomes that do not contain genes, but are important for cell division. When cells divide, the DNA with all the genetic information about us replicates. With cell division each copy of our DNA ends up in a new cell, but the telomere gets shorter with every cell division. The enzyme telomerase is able to lengthen our telomeres. A healthy Mediterranean diet, regular exercise, not smoking cigarettes, sleeping 7 or 8 hours every night are all factors that stimulate elongation of our telomeres. When telomeres are short, they can no longer divide, but the cells turn into senescent cells. They no longer divide, but they stay metabolically active and are significant in the diseases of the aging. They cause osteoarthritis, hardening of the arteries and cancer.

Mice with hyper-long telomeres live much longer than control animals and they have lower LDL cholesterol levels.

Animal studies confirm that short telomeres mean shorter lifespan

There were animal studies that showed that telomeres shorten more slowly in long-lived birds and mammals.

A study looked at the telomere shortening rates of different animal species. They found that those species that had the fastest telomere shortening rate were also the ones with the shortest life span.

Shorter telomeres can also cause several chronic health conditions.

Telomerase helps to keep telomeres from shortening

An important ingredient in every body cell is the enzyme telomerase. It attaches to telomeres and adds DNA to telomeres thus elongating them. Many healthy lifestyles increase telomerase and help shortened telomeres to get longer again.

What preserves the length of your telomeres?

I have previously reviewed factors that elongate telomeres. Here is a summary of this information.

Telomere length enhancers

  1. Lifestyle changes can have positive effects on telomere length. Examples are smoking cessation, weight loss and stress reduction.
  2. Dietary changes: we know that fish oil (omega-3 fatty acids) supplements elongate telomeres as does a low-fat diet.
  3. Supplements like vitamin D3, antioxidants (vitamin C and E) and astragalus (TA-65) elongate telomeres as well.  The astragalus supplement, TA-65 showed a significant elongation of telomeres after 12 months while controls lost telomere length.
  4. Exercise: in a 24-week experiment of care workers regular aerobic exercise increased the telomeres by 67.3 base pairs.
  5. Bioidentical hormone replacement in aging people: when hormones are missing after andropause and menopause, the natural hormones need replacing, or the telomeres are shortening.
  6. High cortisol levels cause telomere shortening.
  7. Human growth hormone elongates telomeres via telomerase activation.
  8. The fasting mimicking diet (FMD) was shown to extend life and telomeres as well.

Conflicting research about longer telomeres

A publication in the New England Journal of Medicine dated May 4, 2023 showed that patients with a POT1 mutation had long telomeres.  This mutation caused cancers, brain tumors, B- and T-cell lymphomas and bone marrow cancers. The long telomeres facilitated cancer growth. Normally this type of mutation is rare and in patients without this mutation long telomeres would lead to longevity.

Dr. Joshua Berkowitz, the Medical Director of IV Boost UK, said that further research needs to focus on the following: “Identifying genetic and epigenetic factors that contribute to aging and longevity, understanding the role of the microbiome in aging and longevity, and investigating the role of senescent cells in aging and age-related diseases.”

Telomeres can Protect you from Premature Aging

Telomeres can Protect you from Premature Aging

Conclusion

Our telomeres are needed for cell division. When telomeres get shorter with age there is a consensus that this leads to a potentially dangerous situation. The cells turn into senescent cells. They no longer divide, but they stay metabolically active and are causing the diseases of the aging. These are osteoarthritis, hardening of the arteries, cancer and many more. On the other end of the spectrum with regular exercise, a Mediterranean diet and a normal weight, telomeres can get elongated, which for most people means a longer life expectancy. However, recent research showed that patients with a POT1 mutation are vulnerable to facilitating cancer growth and premature death. Fortunately, the POT1 mutation is rare. Future research will clarify what the safest way is to achieve longevity.

Nov
07
2020

Removal of Senescent Cells Can Extend Life

Several animal and human studies by the Mayo Clinic showed that removal of senescent cells can extend life. Researchers Xu et al. showed in 2018 that senescent cells weaken the body. Senescent cells are damaged cells that are still living. They can cause the release of inflammatory cytokines. The researchers showed in mouse experiments that intermittent senolytics increased life expectancy by 36%. Senolytics are drugs that dissolve senescent cells; the senolytic cocktail consisted of dasatinib plus quercetin.

In these mouse experiments their risk of dying was reduced by 65% compared to control mice that did not take senolytics.

Senescent cells causing premature aging

In the past 5 years research on aging and on chronic diseases made a lot of progress. Researchers realized that the accumulation of senescent cells is what causes both. All this happens because the process of apoptosis, the removal of dead cells, is impaired in the aging person. It appears that in older age there is a problem with dying cells and their removal. Instead they linger on and start producing cytokines, which cause inflammation. This can damage other cells and lead to organ failures. All this explains why older people often get chronic diseases and do not reach their normal lifespan. The accumulation of senescent cells also blocks regenerative factors that improve one’s health.

Senolytics

Dasatinib is a kinase inhibitor that was developed to treat acute myelogenous leukemia in adults and children. Researchers did animal experiments with a combination of dasatinib and quercetin for several years. They also have started smaller pilot clinical trials in humans. It appears that the human findings are very similar to the animal findings. But more research is needed to answer questions about side-effects and effects of removal of senescent cells.

Details about animal experiments with senolytics

The Mayo Clinic research showed that old mice treated with senolytics (dasatinib and quercetin) live 36% longer than controls that did not receive senolytics. Another part of this series of experiments showed that senescent cells are indeed what kills prematurely. They took senescent cells from old mice and transplanted them into young mice. Soon the young animals showed deterioration health wise and they died prematurely. Another control group were older mice that received senescent cells from old mice. They too died prematurely. Treatment with senolytics (dasatinib and quercetin) improved physical functioning and also survival.

Details about human trials regarding senolytics

For three days 11 participants received senolytics (dasatinib and quercetin). The effect of the drugs was evident for 11 days. The subjects took 100 mg of dasatinib daily and 500 mg of quercetin twice per day for 3 consecutive days. This dose was repeated twice more on a weekly basis for a total of 3 weeks. These patients had idiopathic pulmonary fibrosis. This is an incurable disease where senescent cells accumulate. These patients showed significantly improved gait speed, walking endurance, chair rise test performance and scores of other physical performances. All this occurred on day 5 after the initial dose of senolytics.

Alternative senolytics, so removal of senescent cells can extend life

Dasatinib as a senolytic has significant side effects.

For this reason, researchers looked for alternatives. Theaflavins, isolated from black tea fits this bill. It is non-toxic, but it is also effective as a senolytic. Researchers from Life Extension have developed a senolytic product containing theaflavins and quercetin. Instead of regular quercetin they included quercetin phytosome, which has 50-times more potent bioavailability. One capsule contains 74 mg of quercetin phytosome (the equivalent of 1250 mg of regular quercetin) and 275 mg of theaflavins.

Discussion

Future research needs to show whether or not the Life Extension senolytic indeed does what it promises. It claims that only one capsule per week stimulates apoptosis, reduces cytokines and increases longevity. I would like to see a clinical study that examines all these parameters. One measure of longevity is to determine the length of leukocyte telomeres. All the other laboratory tests are readily available. Research in this field will certainly continue and scientists will likely develop other senolytics.

Removal of Senescent Cells Can Extend Life

Removal of Senescent Cells Can Extend Life

Conclusion

The accumulation of senescent cells causes both aging and chronic diseases. Research showed that in older age the process of apoptosis, the removal of dying cells, is incomplete. As a result dying cells accumulate. They produce inflammatory cytokines, can damage other healthy cells and lead to chronic organ failure. In addition, cancer cells can develop and the patients can die prematurely. Senolytics are substances that clear out senescent cells. In mouse experiments they have already led to improved survival and health. Clinicians performed a clinical trial on patients with idiopathic pulmonary fibrosis, which is an incurable disease where senescent cells accumulate. They showed significantly improved gait speed, walking endurance, chair rise test performance and scores of other physical performances. One pill once per week with dasatinib and quercetin can achieve this. More research in this area can clarify why senolytics work and what the side effects are.