There are studies underway that focus on anti-ageing drugs -such as metformin and nicotinamide adenine (NAD+)- as well as the molecules that elongate telomeres -such as TA-65-.
That is to say, drugs are already arriving on the market: anti-ageing drugs are no longer science fiction. The latest scientific advances have opened a way for us to fight against the effects of time on our bodies. In this post we will discuss the concept of anti-ageing medicine or Age Management Medicine and what we know about the ageing process and how we can better manage how we age.
Dr. Iván Moreno – Neolife Medical Team
“Gerontology”, “Age Management Medicine” and “Rejuvenation Medicine”, the new medical subspecialties that are on the frontline in the fight to slow ageing.
The concept of anti-ageing medicine in the 90s was based fundamentally on the advances being made in terms of the aesthetic treatment. The promise to rejuvenate the patient, to provide external beautification, which is something some people would consider worthy in itself, but the external aesthetic improvement did not avoid the harsh reality: we age at a speed akin to 60 minutes per hour. We may have had a more beautiful smile, a smoother and brighter looking skin and shinier hair, but we were weakened all the same by the same lack of energy and loss of muscle mass, the same joint pains and memory problems. The multiple diseases that deteriorate our quality of life continued to appear throughout the 90s.
The initial conception of anti-ageing medicine tarnished the concept itself, so that for years preventive medicine developed yet anti-ageing medicine was treated with much skepticism. So much so that those that have continued to work in this field have changed their focus to subspecialties such as:
- “Gerontology”, which is the science of studying ageing from the perspective of geriatrics (healthcare for the elderly). At a more fundamental research level (cells and laboratory animals) they are called Bio-gerontologists. Some well known gerontologists such as Aubrey de Gray, Leonard Hayflick or in our country Dr. María Blasco (in one of her numerous fields of research).
- “Age Management Medicine”, which applies to today’s discovery can be applied to real clinical practice and is intended to highlight the concept of “piloting or directing ageing to ensure that we can all life out our later years to our full potential”. Although in Spain Neolife remains the pioneer in this research, there are several American institutes and medical associations such as the AMMG 1 or the A4M 2 that for years have been providing and perfecting this type of assistance.
- “Rejuvenation Medicine”, refers to an experimental concept that directly seeks to turn the clock back on our skin and the tissues behind that -although it is often in newspaper headlines and will be a revolution in a few years time- at the moment it does not seem to have a practical or powerful application. There are companies like Calico 3, the chair of Exponential Medicine at Singularity University 4 (participated in by Google, Deloitte and NASA) and the SENS foundation 5, amongst many others.
Beyond the name changes, the genuinely revolutionary thing that has taken place in recent years is the shift in focus: understanding that ageing is a disease in itself, and that many of what we now know as “diseases” (atherosclerosis, dementia, osteoarthritis, sarcopenia etc.) are only the consequences of ageing. In the past when medicine has been adopted to this approach and focused on other problems – solutions have been discovered.
The first step was to better understand the mechanisms that make our body age, and that, paradoxically as it may seem, has not been studied at all until these last 30-50 years. The reason is that it is widely understood as a normal part of ageing. The expected changes we are all aware of … but resignedly so.
The fundamental mechanisms through which ageing takes place are very well illustrated in a great article 6 by a team of Spanish researchers that marked a milestone in bio-gerontology. Specifically, there are 9 mechanisms:
- Genetic instability: DNA deterioration impacts on cellular and mitochondrial functioning. There is evidence that up-regulation of repair mechanisms prolongs survival chances.
- Telomeric shortening: ageing causes the ends of chromosomes to shorten, producing an increasingly “aged” behavior on a cellular level; fewer cell divisions take place and tissue regeneration occurs less often and consequently disease is more prevalent.
- Epigenetic alterations: the “assembly instructions” that are present in our genome do not determine our entire health. There are many mechanisms that allow us to interpret our score for better or worse and these can be used to determine whether such mechanisms will facilitate or hinder the onset of diseases to which we are predisposed.
- Loss of proteostasis: the proteins of our body are in a constant cycle of creation, deterioration and disposal. The loss of such balance can produce an accumulation of protein waste in numerous organs and damage internal functions. In the brain this can lead to diseases such as Alzheimer’s and Parkinson’s.
- Deregulation of sensitivity to nutrients: over the years our body has progressively worse reactions to nutrients, becoming resistant to insulin and other hormonal factors. Caloric restriction or the simulation of the same through the use of drugs has been shown to increase longevity; also hormonal replacement has been shown to fight the effects of ageing on select tissues.
- Mitochondrial dysfunction: mitochondria are the “furnaces” of cells where the nutrients are oxidized (burnt). Dysfunction in this regard causes oxidative stress to become de-regulated and can accelerate the ageing process.
- Cellular senescence: in healthy tissue, when a cell is damaged the programmed cell death (apoptosis) is activated so that the cell is replaced by a new one. However, when this mechanism is altered, the tissues can accumulate a large number of ageing cells which are inefficient and in the long term can cause the tissue / organ itself to stop working properly.
- Exhaustion of stem cells: the repairing of damaged cells and the maintenance of our body in perfect condition is dependent upon stem cells. These include mechanisms that ensure a greater chance of survival and prolonged reproductive capacity. The exhaustion of such cells means that we are unable to regenerate properly after a certain age.
- Alteration to intercellular communication: the alteration which takes place within the hormonal systems, inflammation and the loss of blood stimulating factors mean that the effects of ageing go beyond a specific cell and can be transmitted to another.
Once such mechanisms are understood, we will be able to identify numerous therapeutic targets for which drugs and other such interventions can then be used (many of which are undergoing trials and research now). This will ultimately allow us to slow down, stop or even reverse the ageing process. In the last 20 years great advances have been made in our knowledge and a multitude of medical interventions have already been outlined that have allowed us to increase the longevity or healthy life expectancy of laboratory animals and, even tentatively, in humans.
The last stage is for society to carry out a number of studies to demonstrate the efficacy of such interventions on humans, that is to say, to demonstrate real, resounding results without serious side effects that would otherwise limit their use. There are already ongoing studies in this regard -such as the TAME 8 (Targeting Aging with Metformin)-, as well as the preliminary results of studies recently completed -including nicotinamide adenine (NAD+) 9 and the use of molecules that lengthen telomeres (such as TA-6510,11)-. This is no longer science fiction: these drugs are coming.
Perhaps this whole process may seem like a very long road which will ultimately lead us to a situation where – with luck – our grandchildren can benefit from our advances, but the truth is that there is an exponential growth in scientific institutions and companies that are dedicating themselves to tackle what will be the greatest health challenge of our time: how to achieve greater health and autonomy in the last third of our lives and how to live even longer.
There is a revolution coming that is not purely scientific (which has long since been and gone), but clinical, which will change the relationship between doctors and patients forever. It will change the prism of how we operate from a focus on health to one involving the optimization of health and away from the disease towards the remedy.
Whilst we wait on the great advances in anti-ageing to materialize, we must take action now to enhance hormone replacement therapy, advanced supplementation, exercise programs, weight loss and caloric restriction…
And what can we do in the meantime? Admittedly, we could wait impatiently with our arms crossed, but we WON’T.
There are many measures that have already demonstrated a beneficial effect on all mechanisms of ageing we have outlined. At Neolife we believe in using a comprehensive approach that, following an individualized assessment, allows us to adapt all of our resources to helping our patients. Caloric restriction, weight loss, exercise programs, improvements to oxidative metabolism, hormonal replacement therapy to maintain optimal levels, advanced supplementation…all have, of course, an important role to play in slowing down our long-term deterioration and achieving optimal health.
In summary: there is a fascinating path ahead of us in terms of anti-ageing, with avant-garde treatments that can be applied now and a future full of new treatments to look forward to once they have been thoroughly tested.
At Neolife we strive to be on the cutting edge of medical science in the fight to delay or stop the ageing process. We follow a bold but critical approach when evaluating developments and we always apply pragmatic clinical perspective.
New discoveries are intellectually fascinating but sometimes they can also appear ethereal and distant and leave us just as alone and unable to stop our deterioration as we were before the discovery. Our vocation is to turn scientific advances into a modern assessment of health that can be utilized to provide specific and individualized treatment programs to each individual. We want to ensure that this revolution has a rigorous, practical and, above all, human character.
If bio-gerontologists are the scientists behind this revolution, we shall endeavor to be the clinicians who interpret the medicine with rigor and ensure that we apply the principles to the individual concerned. We shall continue to humanize this discipline and sublimate it into what is already a new medical art: the personalized preventive medicine, the optimization of medicine, the Age Management Medicine.
(6) López-Otín, C., Blasco, M. A., Partridge, L., Cell, M. S., 2013. (2013). The hallmarks of aging. Elsevier, 153(6), 1194–1217. https://doi.org/10.1016/j.cell.2013.05.039.
(7) Image in open access, courtesy of Cell journal. Downloaded from https://www.cell.com/cms/attachment/2038216256/2052455734/gr1_lrg.jpg.
(9) Dellinger, R. W., Santos, S. R., Morris, M., and, M. E. N. A. (2017). Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD+ levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study. Npj Aging and Mechanisms of Disease, 3(1), 1–9. https://doi.org/10.1038/s41514-017-0016-9
(10) De Jesus, B. B., Schneeberger, K., Vera, E., Tejera, A., Harley, C. B., & Blasco, M. A. (2011). The telomerase activator TA-65 elongates short telomeres and increases health span of adult/old mice without increasing cancer incidence. Aging Cell, 10(4), 604–621. https://doi.org/10.1111/j.1474-9726.2011.00700.x
(11) Salvador, L., Singaravelu, G., Harley, C. B., Flom, P., Suram, A., & Raffaele, J. M. (2016). A Natural Product Telomerase Activator Lengthens Telomeres in Humans: A Randomized, Double Blind, and Placebo Controlled Study. Rejuvenation Re-search, 19(6), 478–484. https://doi.org/10.1089/rej.2015.1793
(12) Image in open access, courtesy of Longevity International. Downloaded from Longevity International – https://daks2k3a4ib2z.cloudfront.net/581ba14cc9b0d76c5dcededf/5a01c612ba3798000177aa14_Science%20of%20Longevity%20MindMap.pdf
(13) Free access in PubMed Central – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340807/figure/f1/
(14) Garatachea, N., Pareja-Galeano, H., Sanchis-Gomar, F., Santos-Lozano, A., Fiuza-Luces, C., Morán, M., et al. (2015). Exercise Attenuates the Major Hallmarks of Aging. Rejuvenation Research, 18(1), 57–89. https://doi.org/10.1089/rej.2014.1623
(15) Jacob ME, Yee LM, Diehr PH, et al. Can a Healthy Lifestyle Compress the Disabled Period in Older Adults? Journal of the American Geriatrics Society. 2016;64(10):1952-1961. doi:10.1111/jgs.14314