“Immortalists”, “life extensionists”, “health spanners”; these are names given to a group of optimists that want to put an end to the current paradigm of getting old. Living forever may not be the goal for most advocates; however, there are many who believe that we can live decades or even centuries longer without the typical chronic diseases that now plague our older population. And while some are lying on magnetic mats or devouring over 100 pills a day to make it happen, medical researchers, physicians and even biotech companies are stepping in to grab their fair share of the billions of dollars that are being spent on technologies and products to ward off aging.
Aesthetic Medicine and the Art of Rejuvenation
Today’s sophisticated patients enjoy the remarkable benefits of aesthetic medicine and have now turned their attention to improving their health to feel as good as they look. In fact, according to a study published in the Journal of the American Medical Association, 53% of the patients sought cosmetic surgical procedures in order to protect their health.1 It seems that along with the physical aspects of aging, such as wrinkled skin or atrophied muscles, the diseases of aging are also on the minds of mature people. Today’s patients desire to look great as they live longer, but they also desire to live healthier, too, which has led to some interesting developments.
Geroscience is a new field of medicine that goes beyond the traditional approach of treating individual diseases. Instead of simply managing disease and living longer, scientists and medical professionals are actively researching how to extend the number of healthy years, or what some would call the health span. And things get even more interesting from here.
Recently, a joint proposal was submitted to the World Health Organization (WHO) to classify aging as a disease.2 Because aging fits the disease criteria of the WHO, the authors suggested that aging can be recognized as a pathological process, which can be treated. The result was the addition of an extension code for age-related disease, XT9T, by the WHO. Today, researchers are beginning to focus on treating the aging body as a whole unit as opposed to treating individual diseases.
The Fountain of Youth
Aesthetic medicine and specialized cosmetic treatments ease the extrinsic signs of aging with techniques such as promoting collagen production in mature patients or repositioning skin to a more youthful location. The effects are remarkable with patients not only looking younger, but feeling more confident as they gain a higher sense of self-esteem. Some physicians and researchers believe the fountain of youth can be found in modern medical advancements to improve one’s intrinsic, or internal, age as well.
On one extreme are people some refer to as “immortalists” that believe death is an option, if only they can find the key. This group believes the body is a machine and just like other machines, parts wear out and need replacing. While most researchers do not believe in living forever, some affluent investors like Jeff Bezos are gambling billions of dollars to find the secret to immortality. Investing in biotech companies is proving to have a payoff, if not with immortality, then at least with life-extension.
Cryonics has yet to prove that humans can be resurrected from death, but cryo-surgery is being deployed to destroy tumors and cancer cells. Cryotherapy is indeed in common use to treat sports injuries and at least one study is showing promising results with whole-body cryotherapy as an early intervention for mild cognitive impairment.3
Other treatments like ozone saunas, vitamin IV drips and hormone cocktails are used by life-extension and health enthusiasts, but still have not proven to be a path to immortality and it is uncertain that any of these can ward off the diseases of aging. Advancements in medical research are encouraging, however. For example, it is possible that epigenetic reprogramming may help reverse gray hair, fade wrinkles and even promote an improved immune response for quicker healing in the near future.
Epigenetics and Cell Reprogramming
Joseph Raffaele, MD, founder of Raffaele Medical and PhysioAge Health Analytics, and a diplomat of the American Board of Age Management Medicine (New York, N.Y.) helps his patients maintain their health span for as long as possible. He explained that age management medicine is rapidly advancing on many levels, “It is a field whose basic premise is to keep the patient as healthy for as long as possible, to maintain what is called the health span. The idea of age management or longevity medicine is first and foremost to change that and maintain a high quality of life for those years.”
According to Dr. Raffaele, researchers who work in geroscience have identified nine hallmarks of aging, including mitochondrial dysfunction, epigenetic alterations and telomere attrition. “DNA methylation is an epigenetic mechanism that controls gene expression,” he explained, “and this mechanism is the most accurate and widely used biomarker of aging.”
Researcher and geneticist Steve Horvath created a concept known as the epigenetic clock, or the Horvath Clock. “We can use this to learn whether a person’s gene expression is that of a younger person or an older person,” Dr. Raffaele added. “The TAME trials will attempt for the first time to prove a drug may actually treat aging and not only a disease.”
Metformin and the TAME Trials
TAME stands for Targeting Aging with Metformin and is one of the few studies recommended by the NIH-funded Geroscience Network, thanks to its high safety and low cost. Dr. Raffaele explained that Metformin is the first line antidiabetic drug that improves insulin sensitivity and may increase lifespan in older adults. “Retrospective and observational studies have indicated that older patients who take Metformin for diabetes seemed to have a lower risk of major chronic diseases and actually live longer compared to people who are similar to them but don’t have diabetes and are not taking Metformin. It appears that Metformin attacks one of the fundamental aging processes which is a deregulated nutrient sensing,” he reported. “The hope is that giving this medication will stall the first appearance of a chronic disease,
reduce the number of chronic diseases, and potentially lengthen life rather than going after a single disease.”
Telomeres as an Indicator of Longevity
Telomeres, the protein structure at the end of chromosomes, protect against chromosome degradation and maintain integrity of the genome. The length of telomeres is linked to life span, as they seem to shorten with age, as well as other factors such as stress, diet or obesity. “You can think about telomeres as a molecular clock within your cells that ticks away until they get too short and then they cannot divide anymore and become senescent,” Dr. Raffaele explained. “It is thought that if you could do something to stop the shortening of telomeres from occurring, or lengthening them again, you could slow down or reverse the aging process and both of those things have been done in various types of studies.
“Ronald Tinho did a study in 2011 where he mapped out telomerase and the mice got older faster,” Dr. Raffaele continued. “But then he was able to turn telomerase back on in older mice and all the gray hair, loss of smell and shrinking organs were reversed. It seems that turning on telomerase and lengthening telomeres has reversed aging in mice models, but not in humans yet. However, many studies have shown that slowing down the shortening of telomeres is associated with many health benefits such as delaying chronic diseases.”
Another study Dr. Raffaele shared involved a compound extracted from Astragalus membranaceus known as TA-65, which seemed to improve markers of cardiovascular disease risk.4 But even more exciting were studies where it seemed to lengthen telomeres. “About 60% to 70% of the adult population have cytomegalo virus, or are CMV-positive,” he explained. “It was once thought to be benign, but it does age your immune system more rapidly. A randomized controlled trial with CMV-positive subjects showed that TA-65 increased telomere length over nine months significantly and statistically in comparison to a loss of telomere length of those who were taking a placebo.”5
With today’s current research, Dr. Raffaele feels optimistic. “What I find exciting are the gene therapy trials with telomeres and using gene therapy to turn on the right genes, stimulate telomerase production, lengthen telomeres by 30% to 50% and have major effects on the aging process. Instead of just treating the diseases, the underlying cause is being addressed, which is the aging process. I think the future is bright.”
A Vaccine for Aging
Tohru Minamino, MD, the director of Cardiovascular Medicine at Juntendo University Hospital (Tokyo, Japan), is the principal investigator for the Core Research for Evolutional Science and Technology (AMED-CREST). While studying telomeres and the effects on vascular aging at Harvard Medical School, Dr. Minamino clarified that senescent cells accumulate in the organs such as the heart as a result of aging, and the accumulation of senescent cells leads to the progression of chronic diseases like diabetes and heart failure.
Today, Dr. Minamino leads the effort in furthering a vaccine for human use that targets and eliminates senescent cells, which some refer to as the “zombie cells” that contribute to aging. So far, the vaccine has been successful on arterial stiffening in mice models and they are hopeful it will work in other areas, as well.
“We tested the effects of senolytic vaccination on diabetes and found that it improved glucose metabolism. We also found that vaccination improved frailty and extended lifespan of premature aging mice,” Dr. Minamino clarified. But future developments could prove even more beneficial. “We believe the senolytic vaccine could be effective for other age-related diseases including dementia, sarcopenia, lung disease, kidney disease and osteoarthritis, in which accumulation of senescent cells has been reported.”
Mice models are just the beginning as Dr. Minamino and fellow researchers believe the research will open doors to allow physicians to customize treatments. “In the future, we may be able to determine types of senescent cells by imaging techniques such as PET-CT, and therefore choose the senolytic treatment or vaccine most suitable for each type of senescent cells, disease and individual.”
Mitochondrial Dysfunction
Mark Tager, MD, co-founder and CEO of ChangeWell Academy (Rancho Santa Fe, Calif.) has authored the book, Feed Your Skin Right: Your Personalized Path to Radiant Beauty, in which he focuses on mitochondrial dysfunction, one of the hallmarks of aging. According to Dr. Tager, this condition is associated with age-related diseases such as type 1 diabetes, cardiovascular disease and Alzheimer’s disease. As we age, mitochondria become less plentiful and less efficient. Dr. Tager emphasized aging mitochondria produce more Reactive Oxygen Species (ROS), and the process of mitochondrial dysfunction is one of the root causes of both extrinsic as well as intrinsic aging.
“Damaged mitochondria are involved in the loss of skin elasticity, excessive pigmentation and the development of fine lines and wrinkles,” Dr. Tager expressed. “These organelles become damaged as a result of oxidative stress related to normal aging, but also as a consequence of chronic inflammation and DNA damage related to smoking, UV radiation and pollution exposure. A theory – the Defective Powerhouse Model of Premature Skin Aging – suggests that inadequate energy production by the mitochondria of dermal skin cells (fibroblasts) leads to structural and functional alterations in the skin.”
To date, lifestyle factors such as diet and intelligent nutritional supplementation are known to support the health of mitochondria. According to Dr. Tager, some of the most well-researched mitochondrial enhancing supplements include alpha lipoic acid, arginine, carnitine, citrulline, NAD+, coenzyme Q10, B vitamins, vitamin C and magnesium.
At the same time, exercise, electrical stimulation and certain hormones encourage mitochondrial biogenesis and may enhance mitochondrial mass. This has led some researchers to believe that mitochondrial biogenesis may be a potential target for treatment of the associated chronic diseases.6
Dr. Tager shared that physicians and practitioners should have intelligent discussions with their patients to help them separate fact from hype while offering therapies that can add quality years to their lives. “The goal of an integrative approach to medicine and aesthetics is to slow down this process and to help patients remain vital as long as possible. The most efficacious treatments are rooted in helping our patients make healthy lifestyle choices: diet, exercise and stress management.
“In allopathic medicine today we have ‘a pill for every ill.’ We don’t want to carry this mindset into ‘a supplement for every symptom,’” Dr. Tager continued. “I believe that practitioners should stay abreast of the longevity research but evaluate some of the newer treatments with a moderate dose of scientific skepticism.”
References:
1. Maisel, A., Waldman, A., Furlan, K., Weil, A., Sacotte, K., Lazaroff, J. M., Lin, K., Aranzazu, D., Avram, M. M., Bell, A., Cartee, T. V., Cazzaniga, A., Chapas, A., Crispin, M. K., Croix, J. A., DiGiorgio, C. M., Dover, J. S., Goldberg, D. J., Goldman, M. P., Green, J. B., ... Alam, M. (2018). Self-reported Patient Motivations for Seeking Cosmetic Procedures. JAMA dermatology, 154(10), 1167–1174. https://doi.org/10.1001/ jamadermatol.2018.2357
2. Khaltourina D, Matveyev Y, Alekseev A, Cortese F, Ioviţă
A. Aging Fits the Disease Criteria of the International Classification of Diseases. Mech Ageing Dev. 2020 Jul;189:111230. doi: 10.1016/j.mad.2020.111230. Epub 2020 Apr 3. PMID: 32251691.
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4. Fernandez ML, Thomas MS, Lemos BS, DiMarco DM, Missimer A, Melough M, Chun OK, Murillo AG, Alyousef HM, Medina-Vera I. TA-65, A Telomerase Activator improves Cardiovascular Markers in Patients with Metabolic Syndrome. Curr Pharm Des. 2018;24(17):1905-1911. doi: 10.2174/138161282 4666180316114832.
5. 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 research, 19(6), 478–484. https://doi.org/10.1089/rej.2015.1793
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