Issue : August / September 2018

Elite Health by Dr Pisuth Lertvilai




Research into anti-ageing medicines and supplements has taken great strides and may be close to showing evidence of being able to add years to the human lifespan


      It has long been a profound human need to search for immortality. Although it seems no closer to realization, we never surrender. This has happened from ancient times to the present. Mythology in former times mentioned a Fountain of Youth, a spring that restores the vitality of anyone who drinks or bathes in its waters. Tales of such a fountain have been recounted across the world for thousands of years, mentioned by many famous writers and the indigenous peoples of the Caribbean during the Age of Exploration, who spoke of the restorative powers of the water in the mythical land of Bimini.


      In this article, I will discuss the possibility of extending human life through ingredients that the scientific world is now exploring.


Mechanism of Ageing

     Ageing is not an inevitable part of life because, theoretically, all cells contain a DNA blueprint that could keep a body functioning forever. Some marine creatures such as American lobsters (Homarus americanus) are biological immortals, these living beings do not age. For humans, we naturally age and when we age, a wide variety of age-related problems, such as loss of muscle tone, dizziness, falls, dementia, loss of eyesight – all of those things begin to attack our bodies and organs. Humans succumb to these, ail and die.


     Over our lifetime, billions of cell divisions must occur to keep our bodies functioning correctly and the more times cells divide the more errors will happen in the process. As cell problems grow, the body can no longer repair the damage. In the case of cancer, cells no longer have the ability to get rid of mutations, and tumours grow. In Alzheimer’s, the brain can not clear the plaques that form on brain cells, and dementia develops.


     Are we getting closer to the protocol of having eternal life or at least living beyond a century? Despite the failure to find a fountain of youth, the scientific world has reported some interesting findings that may lead to proper longevity. To mention one method, we have confirmed in repeated controlled trials that calorie restriction (CR) – taking in less food than what we theoretically need – can assist in improving the efficiency of organs and extend life. The results of CR in life extension have been conducted and confirmed starting from small creatures like worms, and moving up to rats. A positive outcome of CR was likewise confirmed when scientists finished CR trials over 20 years on a group of monkeys, close genetic relatives to humans. CR has also been sporadically tested on humans in trials and the outcome has never altered. Therefore, CR, at present, is the best documented method of slowing and reversing biomarkers of human ageing. I will talk more on CR in a separate article dedicated to the subject.


      We then explore whether the world has found any anti-ageing medicines or supplements. Are they the real thing? Up to now, there are two possible medicines and supplements that may fulfil the never-ending human hope for longevity: metformin and nicotinamide adenine dinucleotide (NAD).




Metformin and diabetes

      Metformin was first described in scientific literature in 1922, by Emil Werner and James Bell, as a product in the synthesis of N,N-dimethylguanidine. In 1929, Slotta and Tschesche discovered its sugar-lowering action in rabbits, finding it the most potent biguanide analogue they had studied. Metformin originates in French lilac or goat's rue (Galega officinalis), a plant used in folk medicine for several centuries.


      Metformin, at present, is the first line of medication for the treatment of type-2 diabetes (diabetes mellitus, or DM), particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. It is not associated with weight gain and is easily taken orally. Metformin works by decreasing glucose production in the liver and increasing the insulin sensitivity of body tissue. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. Metformin is believed to be the most widely used oral medication for diabetes and the cost is not high due to the fact it was discovered long ago and high-quality generics are widely available. The cost of the medicine per month is in a range less than 300 baht.


Metformin and anti-ageing

      Many scientists think the best candidate for an anti-ageing drug is metformin, which increases the number of oxygen molecules released into a cell and appears to boost robustness and longevity. Metformin enhances the activity of an enzyme found within our cells called adenosine monophosphate-activated protein kinase (AMPK). AMPK activation helps mimic the beneficial effects of calorie restriction, which is the method to extend lives described earlier. One of the benefits of practising consistent calorie restriction is a substantial increase in AMPK activity as cells go into semi-starvation mode and increase their survival efficiency.


     When Belgian doctoral researcher Wouter De Haes (KU Leuven) and his team tested metformin on the tiny roundworm, Caenorhabditis elegans, the worms not only aged more slowly but also stayed healthy longer. They did not slow down or develop wrinkles. Scientists moved the trial to mice and found that mice treated with metformin increased their lifespan by nearly 40 per cent and their bones were also stronger. Last year Cardiff University, led by Professor Craig Currie from the university's School of Medicine and his colleagues, found that when patients with diabetes were given metformin, they lived longer than those without, and even should have died eight years earlier on average.


     A new clinical trial called “targeting ageing with metformin”, or TAME, will begin in the US this year. Scientists from a range of institutions are currently raising funds and recruiting 3,000 patients aged 70 to 80 who have or are at risk of cancer, heart disease and dementia. They are hoping to show that the drug slows the ageing process and stops disease. The interim results of this clinical trial are promising.


     Dr Jay Olshansky from the University of Illinois Chicago said, “If we can slow ageing in humans, even by just a little bit, it would be monumental. People could be older, and feel young.” He added, “Enough advancements in ageing science have been made to lead us to believe it’s plausible, it’s possible, it’s been done for other species and there is every reason to believe it could be done in us and this would be the most important medical intervention in the modern era, an ability to slow ageing.”


     Although the perception is that we are all looking for a fountain of youth, his comment relates to increased health span, not eternal life




Nicotinamide adenine dinucleotide

     NAD is a molecule found in all living cells and is critical for regulating cellular ageing and maintaining proper function of the whole body. Levels of NAD in people and animals diminish significantly over time, and researchers have found that upping NAD in older mice causes them to look and act younger, as well as live longer than expected. In March 2017, a study published in the journal Science, by Dr David Sinclair, co-director of the Paul F. Glenn Center for the Biology of Ageing at Harvard Medical School, and his colleagues have put drops of a compound known to raise levels of NAD into the water for a group of mice. Within a couple of hours, NAD levels in the mice had risen significantly, and in about a week, signs of ageing in the tissue and muscles of older mice reversed to the point that researchers could no longer tell the difference between the tissues of a two-year-old mouse and those of a four-month-old one.


     Now scientists are trying to achieve similar results in humans. A randomized control trial (considered the principle or gold standard of scientific research) from a different group of researchers published in November 2017 in the journal Nature found that people who took a daily supplement containing NAD precursors had a substantial, sustained increase in NAD levels over a two-month period.


     Dr Sinclair himself takes an NAD supplement daily. Anecdotally, he says he doesn’t experience hangovers or jet lag like he used to, he talks faster and feels sharper and younger. His father takes it too. His comment was that although his father is now 78 and used to act like Eeyore, now he goes on six-day hikes and travels around the world.


     Dr Sinclair added he is not claiming to have proven that NAD works, but that if it’s going to work, he hopes to be the one to prove it. This research of Prof Sinclair and others may finally reveal whether NAD is the health-extending compound they are looking for.


     To conclude, it is too early to say we have found the ingredients for a fountain of youth, since this would need sound and solid scientific evidence. However, through all the meticulous research conducted with proper methodology, I would say we are now closer to having a reasonable product to fulfil our hope of being able to live and age more gracefully.



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