By Jesica Levingston Mac leod, PhD
A new Harvard study found that we are living longer and better, too. In fact, the life expectancy for a 65 year old in USA grew a lot in the last 20 years: the life expectancy for females is now 81.2 years and for males it’s 76.4 years. The 3 pillars of this improvement are the less smoking, healthier diet and the medical advances. Going straight into the deep science latest developments, two start ups (BioViva and Elysium Health) were in the news recently for their cutting-edge “anti-aging” approaches. The first group to research telomeres gene therapy is Maria Blasco’s group. A study by Bernardes de Jesus et al. demonstrated how telomerese gene therapy in adult and old mice could delay aging and increase longevity, without the collateral effect of increasing the propensity of developing cancer.
In the study, the scientists showed how the treatment of 1- and 2-year old mice with an adeno associated virus expressing mouse telomerase reverse transcriptase (TERT) had beneficial effects on health and fitness, with an increase in median lifespan of 24% and 13%, respectively. Some other benefits included better insulin sensitivity, reduced osteoporosis, improved neuromuscular coordination and improvements in several molecular biomarkers of aging. In cancer cells, the expression of the telomerase is enhanced, giving this protein a bad reputation as having a “tumorigenic activity”. Elizabeth Parrish, the CEO of BioViva, went all the way to Colombia, to receive two gene therapies that her company had developed: one to lengthen the telomeres and the other to increase muscle mass. The results of the treatment were very positive: the telomeres in leukocytes grew from 6.71 kb to 7.33 kb in seven months. As a side note, petite leukocyte telomere length may be associated with several psychiatric disorders (including major depressive disorder) and with poor response to psychiatric medications in bipolar disorder and schizophrenia.
In a nutshell, human telomeres are composed of double-stranded repeat arrays of “TTAGGG” terminating in a single-stranded G-rich overhang. The fidelity of that sequence is maintained by the enzyme telomerase, which uses an intrinsic RNA molecule containing the CAAUCCCAAUC template region and the reverse transcriptase component (TERT), to synthesize telomeric DNA de novo onto the chromosome terminus. The telomeres were named after the greek words télos (end, extremity) and méros (part). Take home message: Telomerase adds DNA to the ends of telomeres and by lengthening telomeres, it extends cellular life-span and/or induces immortalization. The telomerase is not active in normal somatic cells while active only in germ-line, stem and other highly proliferative cells.
Last year, Dr. Fagan and collaborators, published in PLoS One that the transcendental meditation and lifestyle variations stimulate two genes that produce telomerase (hTERT and hTR). Even cheerier news were reported in Nature for thanksgiving: the edible dormouse (super cute, small, long tail mouse – Glis glis) telomere length significantly increases from an age of 6 to an age of 9 years. As they state in the paper “the findings clearly reject the notion that there is a universal and inevitable progressive shortening of telomeres that limits the number of remaining cell cycles and predicts longevity”. These species of mouse skip reproduction in years with low food availability, this “sit tight” strategy in the timing of reproduction might pushed “older” dormouse to reproduce, and this could facilitate telomere attrition, this strategy may have led to the evolution of increased somatic maintenance and telomere elongation with increasing age.
The other company, Elysium, co-founded by MIT professor Lenny Guarente, is focus in the mitochondria and the NAD (nicotinamide adenine dinucleotide). Mitochondria are our energy generators and they get crumbly as we age. Dr. Guarente demonstrated in mice how it may be possible to reverse mitochondrial decay with dietary supplements that increase cellular levels of NAD, like nicotinamide riboside (NR, a precursor to NAD that is found in trace amounts in milk), resveratol (a red wine ingredient) or pterostilbene (present in berries and grapes). Elysium has just realized the results of the clinical trial that was placebo-controlled, randomized, and double-blinded, where they evaluated the safety and efficacy of BASIS (the diateary supplement with nicotinamide riboside (NR) and pterostilbene) in 120 healthy participants ages 60-80 over an eight-week period. Participants received either the recommended dose (250 mg NR and 50 mg pterostilbene) or double the dose. In both cases, the intake of Basis resulted in the increase of NAD+ levels in the blood safely and sustainably, 40% and 90% respectively.
A former Guarante’s postdoc – Dr. Sinclair – has just published in Science the discovery of a NAD binding area in a protein that regulate NAD’s interactions with other proteins related to aging. The Sinclair’s lab reported that the binding of NAD+ to DBC1 (Deleted in Breast Cancer 1 protein) prevents it for inhibiting another protein – PARP1, an important DNA repairing protein. Furthermore, they have shown that as the mice aged, the concentration of NAD+ decreased, and more DBC1 was available to bind to PARP1, culminating in the accumulation of DNA damage. On a brighter note, this process was reversed by restoring higher levels of NAD+. The good news are that NAD+modulation might protect against cancer, radiation and aging.
Although all these advances are great, they won’t make you live longer in the next 10 years, so what can you do to live longer/healthier? Science comes again to answer this question! Harvard studies have shown that living “meaningful lives” helping others, having aims/motivations (and been conscious about the fact that we are taking our own decisions), been grateful, enjoying the present and significant relationships with other humans are key aspects to have a happy live. Obviously, exercising and having natural environments around us, as well as healthy eating are crucial points in a healthy life.
It might be an oversimplification, but 70% of your risk of disease is related to diet: soda and processed food are related with shortening the telomeres. Good news: you can slow down aging with a healthier life style: “Switch to a whole-food, plant-based diet, which has been repeatedly shown not just to help prevent the disease, but arrest and even reverse it” claims Dr. Greger’s, author of the Daily Dozen—a checklist of the foods we should try to consume every day. The super food list includes: Cruciferous vegetables (such as broccoli, Brussels sprouts, cabbage, cauliflower, kale, spring greens, radishes, turnip tops, watercress), Greens (including spring greens, kale, young salad greens, sorrel, spinach, swiss chard), other vegetables (Asparagus, beetroot, peppers, carrots, corn, courgettes, garlic, mushrooms, okra, onions, pumpkin, sugar snap peas, squash, sweet potatoes, tomatoes), beans (Black beans, cannellini beans, black-eyed peas, butter beans, soyabeans, baked beans, chickpeas, edamame, peas, kidney beans, lentils, miso, pinto beans, split peas, tofu, hummus), Berries: (including grapes, raisins, blackberries, cherries, raspberries and strawberries), other fruit (such as apples, apricots, avocados, bananas, cantaloupe melon, clementines, dates, figs, grapefruit, honeydew melon, kiwi, lemons, limes, lychees, mangos, nectarines, oranges, papaya, passion fruit, peaches, pears, pineapple, plums, pomegranates, prunes, tangerines, watermelon), Flax seeds, nuts, spices (like turmeric), whole grains (Buckwheat, rice, quinoa, cereal, pasta, bread) and the almighty: water.
As you can expect, a lot of research is needed to get a magic pill that might boost your life expectancy but you can start investing in your future having a positive attitude, healthy diet, exercising and all the other things that you already know you should be doing to feel better, without forgetting that life is too short, so eat dessert first.
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