In humans, circulating telomerase activity rather than telomeres length is inversely associated with the major cardiovascular disease risk factors. See below.
In the nucleus, telomerase promotes telomere "stability."
In the cytoplasm, telomerase has preservation of mitochondria and antioxidant maintenance as its priority and hTert is actually blocked from translocating to the nucleus.
Beta hydroxybutyrate from lifestyle choices causes telomerase et al of the starvation gene set to be expressed. Telomerase, BDNF, p53-pgc etc.
E.g.. Weekly 24 hour fasting improved age related heart failure EF from 30% to 60% over 8 weeks in mice. BDNF of 30% increased to 100% of normal. BDNF is a proxy biomarker for the starvation gene set expression and by extension telomerase. Therefore fasting weekly increased beta hydroxybutyrate gene transcription of restorative genes including telomerase, a major biomarker of cardiovascular mortality.
Number needed to treat in the mouse study to restore EF and presumptively to reduce "hospitalization and mortality?"
One.
Conclusion of article wrongly emphasizes eating however when we eat and by extension when we do not eat alone produces beta hydroxybutyrate, a ketone from low insulin intervals and increased fat metabolizing intervals. Insulin stores glucose and inhibits lipolysis.
80% of metabolic health is when we eat or how well we metabolize fats and produce beta hydroxybutyrate. Insulin sensitive, exercise, fasting and ppar alpha agonists (such as ursolic acid) consuming persons are metabolically healthy and age slower than their opposites.
It appears logical to the extreme to promote 12 hours daily fasting, 24 hour weekly fasting, exercise and possibly ursolic acid 200mgs for secondary prevention of cardiovascular disease.
Nutrition and lifestyle in healthy aging: the telomerase challenge
In contrast to stem cells which constitutively express low levels of telomerase, normal somatic human cells repress its expression immediately after birth [-]. Thus, for a long time, telomere length has been considered as an indicator of cellular senescence, and a potential biomarker of human aging, but studies supporting this role are still contradictory and inconclusive [,,]. More recent genetic studies in animal models have demonstrated that short telomeres rather than average telomere length are associated with age-related diseases and, their rescue by telomerase is sufficient to restore cell and organismal viability [30,31]. In humans, circulating telomerase activity rather than telomeres length is inversely associated with the major cardiovascular disease risk factors [32]. Thus, another concept is coming up, the “telomere stability”, a quite different concept from telomere length. For example, patients with Alzheimer's disease do not invariably have shorter telomeres, but their telomeres have significant signs of dysfunction [33-38]. Improving the activity of telomerase enzyme -that can add length back to shorter telomeres, and, in the meantime, protect longer telomeres to ensure stability- seems a way to actually turn back the biological clock. Telomerase has also extra-telomeric functions influencing various essential cellular processes, such as gene expression, signaling pathways, mitochondrial function as well as cell survival and stress resistance [40,41]. Therefore, the presence of active telomerase in stem cells, and potentially in all cells, may be helpful for longevity and good health.
Lifestyle factors known to modulate aging and age-related diseases might also affect telomerase activity. Obesity [42], insulin resistance [43,44], and cardio-vascular disease processes [45,46], which are related to oxidative stress and inflammation, have all been linked to shorter telomeres. Smoking, exposure to pollution, lower physical activity, psychological stress, and unhealthy diet significantly increase the oxidative burden and the rate of telomere shortening [47-53]. So, what a better way to counteract the “biological clock” by reactivating telomerase trough diet and lifestyle interventions? There is a recent paper showing that with intensive lifestyle modification, with a low fat diet, regular physical activity, and mental stress reduction (by yoga and meditation), telomerase activity increases significantly in peripheral blood mononuclear cell (PBMC) [54]. Again, people living in the Mediterranean countries have longer and healthier life as compared with people living in other industrialized countries, and we previously demonstrated that they have also claim longer telomeres and higher telomerase activity in PBMC [55]. It is still unclear if there is a single nutrient or a factor responsible of Mediterranean diet anti-aging properties or the whole, single ingredient foods and lifestyle are the key to “healthspan”.
Today, researchers are struggling to find a compound or an “elixir” for long life, while common people are taking dietary supplements with the intent to preserve mental, physical, and emotional health into old age. Most dietary supplement programs include combinations of vitamins, antioxidants, and other constituents, some of which have been shown to have significant health benefits in controlled clinical studies. Specific nutrients provide all the necessary building blocks to support telomere health and extend lifespan. This is the case of folate [56,57], vitamins (B, D, E, C) [58] zinc [59] and polyphenol compounds such as resveratrol [60], grape seed extract and curcumin [61]. Several foods -such as tuna, salmon, herring, mackerel, halibut, anchovies, cat-fish, grouper, flounder, flax seeds, sesame seeds, kiwi, black raspberries, green tea, broccoli, sprouts, red grapes, tomatoes, olive fruit- are a good source of antioxidants. These, combined with a Mediterranean type of diet containing fruits, vegetables and whole grains would help protect our chromosome ends [62-70].
In conclusion, what we eat, how we eat and how much we eat, together with lifestyle significantly, can affect our telomerase/telomere system with a great impact on healthspan. “Similes cum similibus curantur” and in nature is still hidden the secret of healthy and long life whereas telomerase could represent the distinctive target.
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