Telomeres by Lakshika Weerathunge

Telomeres

  • Telomeres do cell replication and protection of chromosomes
  • Telomeres are pink protective pieces of DNA materials at the ends of chromosomes
  • Like the plastic tips on shoelaces, telomeres prevent chromosome ends from fraying and sticking to each other, which would damage genetic information to cause cancer, other diseases, or premature ageing.
  • It has been proposed that telomere shortening may be a molecular clock mechanism that counts the number of times a cell has divided and when telomeres are too short, cellular senescence (growth arrest) occurs.
  • It is believed that shortened telomeres in mitotic (driving) cells may be responsible for some of the changes we associate with normal and premature ageing.

Diseases affected by Telomere shortening

  • Cardiovascular cancer
  • Copd
  • Degenerative disc disease
  • Alzheimer’s
  • Osteoarthritis Rheumatoid
  • Immunity skin aging
  • Macular degeneration
  • Liver Cirrhosis
  • Muscular Dystrophy
  • Cell and Tissue Transplants
  • AIDS
  • Progeria
  • Pulmonary Fibrosis
  • Tuberous Sclerosis

Factors that accelerate telomere shortening

  • Homocysteine
  • Inflammation
  • Oxidative stress
  • Depression
  • Emotional Stress
  • Physical trauma

Telomerase is the enzyme responsible for Re-Building telomeres.

Telomerase activity is observed in fetal tissues, adult germ cells, and tumour cells. Telomerase is turned off in all other cells.

Can reverse the signs of ageing by artificially lengthening the telomere?

Telomerase reactivation reverses tissue degeneration in aged telomerase deficient mice https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3057569/ 

Accumulating evidence implicating telomere damage as a driver of age-associated organ decline and disease risk and the dramatic reversal of systemic degenerative phenotypes in adult mice observed here support the development of regenerative strategies designed to restore telomere integrity.

Researchers found that a healthy lifestyle may result in long telomeres.

Antiaging Intervention Comes of Age

A more direct and so far the only serious attempt to combat aging through telomerase activation and telomere elongation is the use of TA-65, a dietary supplement isolated from the Chinese traditional medicine herb Astragalus membranaceus . This approach opens up the possibility of health and life extension, or even rejuvenation, as has been demonstrated in transgenic animals . Although some expression of telomerase in normal somatic cells in culture was detected, the use of TA-65 did not show significant effects on human subjects during a 1-year trial.However, while there was no or just a slight effect on average telomere length, more important reduction in the proportion of the shortest telomere fraction (>4 kb or bottom 20%) was demonstrated in most subjects. Since these trials were performed over a relatively short period of time, it will take years before some positive effects of TA-65 on health and longevity become more obvious.

https://academic.oup.com/biomedgerontology/article/73/1/39/3828300

Dietary Patterns with Effect on Telomere Length and Aging

An association between telomere length and nutritional status can be seen since birth because exclusive breastfeeding in the first 4–6 weeks of life is associated with longer telomeres in Latino preschool children at 4 and 5 years of age. Later in life various diets show beneficial effects on human health. Among those, reduced calorie intake has raised much attention both among scientists and the general public because it is the only nonpharmacological intervention known to date that slows down the aging process and increases both average and maximal life span in rodents, fish, fruit flies, worms, and yeast .

Calorie Restriction

  • A longitudinal calorie restriction (CR) studies in rhesus monkeys (Macaca mulatta) implied that CR can prolong life span in longer-lived species.
  • These investigations raised the hope that CR might be effective in humans. However, contradictory results were later published which indicated that, while some health benefits were observed, CR had no effect on longevity in these monkeys. 
  • Both studies demonstrated that CR in tested animals delayed the onset of several aging associated pathologies such as diabetes, cancer, cardiovascular diseases, and brain atrophy. 
  • Another study showed that CR does not significantly affect telomere length in the skin and muscle of rhesus monkeys . 
  • Possible differences in the life span of CR animals can be explained by differences in dietary composition, vitamin and mineral supplementation, husbandry, and genetic background. 
  • It was shown that all calories are not the same, and significantly it is the quality of the source of calories that matters 
  • Meanwhile, the effect of CR on humans has been poorly studied. The great number of centenarians and the high average life span of Okinawa women who consumed 15%–20% less calories than mainland Japanese throughout their lifetime may be living proof that moderate CR in combination with a well-balanced diet can have significant effect on human life span.
  • CR in the Biosphere 2 experiment due to unexpected food insufficiency showed that healthy nonobese humans on a low-calorie, nutrient-dense diet show physiologic, hematologic, hormonal, and biochemical alternations consistent with caloric restricted rodents and primates . 
  • Following the first 6 months of the first randomized human trial, it was shown that CR had positive physiological and psychological effects including improvement of several markers of aging. 
  • This was confirmed by a later study where the effects of CR on disease risk and human survival suggested potential benefits for aging-related outcomes . 
  • Although the effect of CR intervention on life span in humans remains to be determined unequivocally, evidence thus far suggests that it can be a successful step to prolonged health span and healthy aging.
  • Without strong proof that long-term CR indeed prolongs human life and the fact that it is very hard for most individuals to practice calorie restriction in an overfeeding environment, later studies have focused on compounds, like resveratrol that mimic calorie restriction metabolism. 
  • The effects of various forms of dietary restrictions, including normocaloric diets with planned deficiencies (in particular macronutrients: proteins or carbohydrates), and time-restricted feeding have also been used as alternative models for impacting telomere length and health span. 
  • Most of these interventions have positive effects on overall health and longevity in model organisms .
  • It has been shown that short-term dietary restriction has multiple benefits in mammals including modulation of inflammatory responses , reduction in cell senescence, and decreases in oxidative stress markers in the small intestinal epithelium and liver in mice. 
  • Recent work suggests that a fasting-mimicking diet (FMD) consisting of cycles of short-term FMD followed by a standard ad libitum diet can produce health benefits in people and extend the life span of mice.
  • The aforementioned evidence suggests that beneficial effects on health span and life span can be achieved by less invasive dietary interventions, rather than CR, which do not require long lasting or overall reduction in calorie intake.
  • While a positive effect of CR on telomere length and telomerase activity in rodents has been well documented , there have been very few reports regarding the association of energy intake with telomere length in humans. A cross-sectional Multiethnic Study of Atherosclerosis that encompasses men and women showed a nonsignificant negative correlation of energy intake with telomere length . 
  • The absence of a correlation between energy intake and telomere length was also found in the Nurses’ Health Study and in elderly Chinese men. In contrast, research conducted on young adults in Jerusalem showed a significant negative correlation of dietary energy and macronutrient intake with both baseline and follow-up telomere length in men only. 
  • It is important to emphasize that the test subjects in this study were younger (age 30–43) than in other reports. Recently an article was published describing the connection of plasma irisin levels and telomere length. Irisin is a hormone released from skeletal muscles after exercise which may induce CR-like effects by increasing energy cost from adipose tissue. Using telomere length as a marker of aging, this study showed a significant positive correlation between plasma irisin levels and telomere length.

Mediterranean Diet

  • In the last 15 years, a lot of attention has focused on the Mediterranean diet, proven to be one of the healthiest diets in the world . It respects all the principles of the healthy antiaging diet mentioned earlier as it is based on the intake of seasonal fruits, vegetables, nuts and seeds, whole grains, olive oil, fish and low fat meat, and dairy products as well as moderate intake of alcohol. 
  • As a result, the Mediterranean diet has been linked to low morbidity, lower occurrence of some chronic, especially cardiovascular diseases and consequently greater longevity. The Mediterranean diet lowers the level of oxidative stress markers and inflammation due to a high abundance of antioxidant compounds such as omega-3 and resveratrol .
  • Importantly, it has a direct positive effect on telomere length
  • Additional confirmation of a positive influence of the Mediterranean diet on telomere length came from a Nurses’ Health Study which is one of the largest research studies into the risk factors for major chronic diseases in women. Adherence to a Mediterranean diet managed to preserve a telomere length that corresponded to 4.5 years of aging which is comparable to the effects of smoking (4.6 years) and physical activity (4.4 years) on the telomere shortening rate.
  • The Mediterranean diet also stimulates telomerase activity in peripheral blood mononuclear cells. If combined with moderate exercise, this diet demonstrates elevated long-term improvement in endothelial microvascular and cardiorespiratory functions, important for both better health and increased life expectancy .

Vegetarian Diets

  • Vegetarians, including vegetarian subgroups, which differ in their degree of avoidance of meat consumption and based on a degree of restriction of other animal products (milk, eggs, etc.), have also been studied for effects on health span and telomere length. 
  • Even though it is perceived as very healthy by the general public, observed consequences of a vegetarian diet are higher intake of antioxidants and lower fat intake but at the same time deficiencies in vitamins B, D, iron, and calcium were also shown. 
  • Over time, conflicting results were reported regarding general health, antioxidant status, and DNA damage observed in vegetarians and so far, no clear conclusions about beneficial effects can be drawn from these studies without a thorough multibiomarker meta-analysis. 
  • As far as telomeres are concerned, there is very little data. One case–control study conducted on an Indian subjects with coronary artery disease showed trend toward longer telomeres in vegetarians compared with subjects on a mixed diet without a statistical significance. Additional research is needed specifically designed to test this correlation.https://academic.oup.com/biomedgerontology/article/73/1/39/3828300

Special Foods 

Nuts and olive oil

  • Along with the consumption of nuts, the study by Meshkani et al.  also showed that olive intake, including olive oil, was positively associated with a longer TL. This finding is consistent with studies that evaluated the association between TL and an adherence to the Mediterranean diet as a proxy measure of olive oil . Furthermore, cumulative evidence supports that dietary olive oil has beneficial compounds against ageing-related diseases and contributes to the maintenance of genomic stability https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570627/
  • Nuts and seeds intake was positively and linearly associated with telomere length. For each 1-percent of total energy derived from nuts and seeds, telomere length was 5 base pairs longer (F=8.6, P=0.0065). Given the age-related rate of telomere shortening was 15.4 base pairs per year (F=581.1, P<0.0001), adults of the same age had more than 1.5 years of reduced cell aging if they consumed 5% of their total energy from nuts and seeds.

https://www.sciencedirect.com/science/article/pii/S1279770723000490

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232155/

Flax

An easy addition to any salad or smoothie, flax is a great source of omega-3s, which are important for both preventing inflammation and building cell membranes throughout the body. Research shows that omega-3s can prevent telomeres from shortening too quickly. One study published in 2010 in The Journal of the American Medical Association looked at the blood levels of over 600 people with stable heart disease. The study showed that the higher the levels of omega-3 in their blood, the less their telomeres declined over five years. Other great ways to get your omega-3s are soy foods, green leafy vegetables, and high quality algae-based or fish oil supplements.

Spinach

This crunchy green leaf is as delicious raw as it is tucked into this delicious Ornish Kitchen Spinach and Mushroom Lasagna, which packs in several other top telomere-saving foods noted here. Besides being rich in fiber and antioxidants that protect telomeres, it tops the list of folate-providers. Folate is a B vitamin that’s required for DNA synthesis, repair, and metabolism within the cell. Folate is also imperative to maintain low levels of homocysteine. High levels of homocysteine can cause inflammation and damage our artery linings, which promotes heart disease. Many studies, including one published in 2016 in Clinical Nutrition Research, have linked folate, B12 and high homocysteine with shorter telomere length. Other good sources of folate are broccoli, asparagus, Brussels sprouts, lentils and beans (soy, pinto, black, navy and kidney), as well as fortified cereal and whole grain products.

Mushrooms

These earthy, light and versatile fungi serve quality Vitamin D, which is associated with telomere length. A study published in 2017 in The Journal of Nutrition showed that those with low Vitamin D (under 50 ) had shorter telomere than those with adequate Vitamin D ( over 50). Other great ways to get your Vitamin D via food are fortified soy and nondairy milks and nonfat dairy and cereals, although supplements may be needed to maintain adequate levels if deficient. See Ornish Living article The Importance of Sunshine to learn more ways to increase your vital Vitamin D.

Berries

Nature’s sweetest, most nutrient-rich finger foods are the perfect way to take in antioxidants that fight cell-damaging free radicals. Research shows that those with higher levels of antioxidants such as Vitamin C, E and selenium tend to have longer telomeres. Fruits and vegetables are the best sources of antioxidants, which is why a plant-based diet is highly recommended. So don’t stop at berries when seeking anti-oxidizing effects: carrots, sweet potatoes and yams, winter squash and green leafy vegetables are packed with them. Tomatoes, citrus, cantaloupe and potatoes with skins provide plenty of Vitamin C. Soy, nuts, and seeds offer Vitamin E and whole grains provide selenium.

Oats

The soluble and insoluble fiber in this traditional breakfast grain promotes blood sugar management and prevents insulin resistance that can damage and shorten telomeres. And paired with the telomere-protective berries, oatmeal offers an added boost of health-promoting fiber. Other ways to get your fiber: whole grains of various types, vegetables, fruit, beans and lentils.

Amla (Phyllanthus Emblica):

Commonly known as the Indian Gooseberry, Amla is known to be a very potent anti-aging fruit. It is a very powerful antioxidant and one of the richest sources of vitamin C, tannins, and gallic acid.

Amla is used in several skincare and hair products owing to its high antioxidant content in the form of vitamin C. As per Ayurveda, it has several beneficial properties:

a. Prolongs cell life

b. Improves cell migration and bindi

c. Improves complexion

Modern research shows that the enzyme telomerase is responsible for maintaining the length of genetic structures called telomeres in body cells. The longer the length of the telomere, the longer our cells can keep dividing to produce newer, healthy cells and the longer we can live.

Recent research studying the effect of Amalaki Rasayana prepared using Amla improves telomerase activity, thus helping maintain telomere length and preventing aging.

Probably, the antioxidants in Amla fight off free radicals that are responsible for aging.

2. Ashwagandha (Withania somnifera):

Ashwagandha, famously known as Indian ginseng, has proven adaptogenic properties. It has been shown to be effective in the management of stress and anxiety, particularly when resulting from dietary and lifestyle issues.

Several studies have been conducted to identify the potential benefits of Ashwagandha. These have shown Ashwagandha to stimulate stem cell proliferation, and boost immunity. It also has antitumor and anti-inflammatory activities.

Thus, Ashwagandha helps in rapid cell regeneration and rejuvenation, which helps delay the process of aging.

3. Shilajit (Asphaltum):

Shilajit, with its botanical name Asphaltum, is one of the most famous Ayurvedic medicine. This blackish-brown substance found between layers of rocks in mountain ranges, particularly the Himalayas, has been known as a rejuvenator for ages.

It is formed by the gradual decomposition of certain plants under the influence of microorganisms. Shilajit is considered one of the wonder drugs and has been used in traditional Indian medicine for several years for general physical well-being, kidney rejuvenation, blood sugar stabilization, urinary tract rejuvenation, anti-aging, enhancing brain functioning potency, hypertension, immune system strengthening, and arthritis.

Shilajit is one of the most researched Ayurvedic remedies and has been shown to have anti-inflammatory activity and help lower anxiety. It also has free radical scavenging activity and a resultant antioxidant effect. Because of these properties, it is a very potent anti-aging agent.

4. Garlic:

Another household name in the culinary world, the humble garlic is known to be power packed with antioxidants and has been extensively researched for the same in the past two decades by Western researchers.

It has been shown to not just prevent or slow down aging but also shown to prevent cancer, improve memory and reduce dementia in the aging brain, prevent cardiovascular disease, enhance blood circulation and rejuvenate the skin, as per evidence.

Allicin is the active ingredient in garlic which bestows on it all these wonderful properties.

5. Turmeric:

The blue-eyed baby of every controversial healthcare research, turmeric contains curcumin which has been examined extensively for its anti-inflammatory and anti-aging properties.

However, there is robust evidence showing its anti-senescence properties on the brain. Evidence supports reduction in aging in the medulla, cerebral cortex, cerebellum, and hippocampus areas of the brain.

One research published in Molecular Nutrition & Food Research found that curcumin induced a stress response in human skin cells called fibroblasts. This leads to redox signaling and the production of a protective effect to further oxidation processes, bestowing an antioxidant shield on the skin.

Researchers continue to look for stronger evidence in Ayurveda and in nature in general for the anti-aging properties of natural plants, minerals, etc. It is prudent to remember that while a long and healthy life is important to achieve your goals, it is more important to make the most of the years you do have and use each day to the fullest.