Dear Future Centenarian,
Until recently, it had not been possible to outline a scientifically supportable approach to reverse biological aging in a meaningful manner. However, over the past 6 years, a number of regenerative technologies have been demonstrated in animal models, and some have been studied in proof-of-concept human trials.
Findings from this research indicate that elderly people may be able to regain a degree of youth and vigor, and alleviate chronic health issues, by counteracting degenerative factors that have recently been well characterized by researchers.
Aging is at least partially reversible right now using existing therapies. The suggested protocol at www.age-reversal.net involves four steps, and we added two more in the past two years:
Lifestyle habits – Step 1:
I have written a lot on this topic over the years… and have made it even easier for you by writing seven e-books, one on each of the lifestyle steps. The best news is, as a subscriber, you can get them for free.
The first two are on Amazon at:
You will find the two e-books attached to this letter. I would be SO grateful if you would leave a good review on each on the Amazon pages.
The remaining five books will be available soon.
mTOR inhibition – Step 2: mTOR inhibition
mTOR stands for mechanistic target of rapamycin. It is a protein found inside most cells and is responsible for regulating cellular growth by sensing and integrating diverse nutritional and environmental cues.
Excessive activation of cell mTOR is implicated in the chronic diseases plaguing our aging population such as cancer, type 2 diabetes, and obesity.
Lowering mTOR activity extends life span in laboratory models by delaying the development of chronic diseases including cancer.
Our very existence—our individual creation and growth into adulthood—was dependent on highly activated mTOR in our cells that fueled their rapid proliferation. With aging or excess calorie intake, most people’s mTOR remains at dangerously high levels of activity long after we’ve ceased growing.
Turning down mTOR delivers big benefits, including turning on autophagy to help rid cells of accumulated debris. Studies in elderly people indicate improvements in immune functions in response to mTOR inhibition.
Aside from very extreme calorie restriction, which is impractical for most people, the most efficient way of suppressing excess mTOR is using a drug called rapamycin in the dose of about 5 mg once a week.
NAD+ restoration – Step 3: NAD+ Restoration
Nicotinamide adenine dinucleotide (NAD+) is a coenzyme essential for cell function and systemic life sustenance.
NAD+ declines with age to the point that by the time humans reach 80 years, they may only have around 4% of the NAD+ levels they did at age 21. It may be a mere coincidence, but, interestingly, the average human lifespan in modern societies today happens to be around 80 years.
As it relates to today’s age-reversal interventions, including cell rejuvenation therapies, most of these therapies are likely to work best in people with optimal levels of NAD+.
I only know of one test that measures your critical NAD+ levels. You can find it at
You may have heard about a study from Harvard Medical School earlier this year that identified a method to reverse vascular aging. This reversal was accomplished by boosting endothelial levels of NAD+ and the cellular protein sirtuin1 (SIRT1).
Resveratrol exerts its beneficial effects mainly by boosting SIRT1. Older people, however, are so deficient in NAD+ that they are unable to fully benefit from resveratrol. That’s because SIRT1 functionality is highly dependent on NAD+.
Methods that remove senescent cells or remove toxic debris from aged cells (autophagy) will be of little benefit if there is insufficient NAD+ to enable continual youthful metabolic activity.
Hence, individuals seeking to delay or reverse certain aspects of aging should take steps to boost cellular NAD+ levels.
Youth factors derived from young plasma or infused stem cells are more likely to induce rejuvenation in response to higher NAD+ levels. We acknowledge the need for more experimental evidence to verify better responses to young plasma/stem cells by boosting NAD+ levels.
A dietary supplement called nicotinamide riboside increases NAD+ blood levels.
However, if you’re over the age of 45, you may want to directly boost your NAD+ levels via intravenous infusion of 500 mg of NAD+ administered every other day for a total of three infusions. Each infusion takes 4-5 hours.
The cost of the infusions can be high, so I use NAD+ patches to bring the cost of NAD+ restoration down considerably. You’ll need a prescription to order. I use Archway Apothecary. Fax 985-801-0801. Phone 985-801-0800.
Senolytics – Step 4: Eliminate senescent cells from your body
As cells reach the end of their life cycle or become severely damaged, most self-destruct via a normal process known as apoptosis.
Some cells fail to undergo this beneficial self-elimination process and instead linger in a dysfunctional “zombie-like” state where they impede organ function, emit damaging inflammatory signals, and thus shorten healthy lifespan.
These “senescent cells” often spread throughout tissues like a contagion and inflict massive damage, which can result in organ failure and degenerative disorders related to persistent low-grade inflammation.
Senescent cells survive by evading apoptotic mechanisms the body normally uses to eliminate them.
Recently published studies reveal that just a few senescent cells transplanted into young mice result in persistent physical decline characteristic of pathological aging.
When senescent cell–laden mice that are the human equivalent of 75-90 years old were given compounds (senolytics) that selectively eliminated senescent cells, there was an alleviation of physical decline. The old mice treated with senolytic compounds lived a remarkable 36% longer.
As it relates to the goal of systemic age reversal by means of a sequential order of regenerative therapies, a logical first intervention is to purge your body of these “toxic” senescent cells.
Senolytic therapy has not only demonstrated profound rejuvenating properties by itself, but may open up opportunities for other rejuvenation strategies to be more effective.
For instance, if you are considering infusions of mesenchymal stem cells, young plasma, or umbilical cord-derived cells/plasma, you want your body to be in a metabolic state that welcomes these pro-youth interventions.
Senescent cells generate a firestorm of destructive inflammatory factors that may result in otherwise powerful therapies being wasted on the task of cleaning up the mess of damaging signaling factors, such factors that could easily have been removed ahead of time using senolytic compounds.
Senolytic therapy by itself is demonstrating impressive regenerative effects. So much so that most self-experimental study subjects are seeking to repeat this intervention after 6 months.
The senolytic cocktail that some of our supporters have been experimenting with is a combination of dasatinib, a well-studied cancer drug, and high-dose quercetin.
This treatment should be done under the supervision of a healthcare provider, although we have not yet heard of any serious side-effects or adverse events from this protocol. Dasatinib and quercetin have demonstrated potent senolytic and subsequent age-reversal properties when used together in appropriate doses.
Stem cell renewal – Step 5:
Stem Cell research has come a long way over the past several years. The trick is finding a credible stem cell clinic that uses the most effective stem cell lines, and also one that is honest. These are not likely to be found in the US, although there are exceptions.
If you find a clinic that you like, be sure to give you examples of treatments they have given that pertain to what you hope to accomplish with yours. Then ask for (DEMAND in a nice way) referrals to at least three relevant patients.
Don’t take no for an answer. If they’re trying to hide something, they may cite “patient confidentially” as an excuse. But if you got excellent results, wouldn’t you share your experience with others once you gave your permission with the clinic for connecting you with their potential patients?
Gene therapy – Step 6:
A cure for aging by 2030? George Church, PhD, the pioneering Harvard geneticist who continues innovating CRISPR gene editing treatments, thinks this is entirely possible.
Meanwhile, combinational gene therapy treatments to start reversing key aspects of the aging process are available today under the informed consent medical tourism model for those who can afford them.
I will have more for you in next week’s letter.
An Overview of Companies Targeting Mitochondrial Dysfunction in Aging
Today’s materials are a helpful overview of the brace of biotech companies working to slow or reverse aspects of mitochondrial aging.
Mitochondria play a central role in core cellular processes and are important in degenerative aging. Every cell contains a herd of hundreds of mitochondria, the descendants of an ancient symbiosis between the first cells and bacteria that could help them survive.
The Future of Human Longevity will be Very Different from the Past
Human life expectancy has increased through two distinct process; firstly a reduction in child mortality, and second a reduction in the burden of damage accumulated over an adult life span.
Control of infectious disease has played a large role in both components of gains in life expectancy. The trend has been slow. In recent decades, something like 0.2 years of life expectancy at birth and 0.1 years of remaining life expectancy at age 60 have been added with each passing calendar year.
At present, the medical research community is shifting from a paradigm in which the mechanisms that cause aging were ignored, to a paradigm in which the mechanisms that cause aging are deliberately targeted.
Targeting of Telomere Lengthening Processes will be the Basis of the Next Generation of Cancer Therapies
Telomeres are repeated DNA sequences that form the end caps of chromosomes. A little of their length is lost with each cell division, and cells self-destruct or become senescent and cease replication when telomeres become too short.
This is a part of the Hayflick limit on cell replication: near all cells in the body can only divide a limited number of times. Stem cells are the first exception, using telomerase to extend telomeres.
The Present Understanding of the Relationship Between Growth Hormone and Longevity
Growth hormone treatments (and other hormone therapies) have a legitimate use in patients suffering excessively low hormone levels due to one or another cause.
They have also long been overhyped and aggressively marketed by the anti-aging medicine community, not a field noted for its adherence to standards of truth and scientific accuracy.
At the same time, the scientific evidence has consistently shown that aging is accelerated by higher levels of growth hormone.
Prevalence of Cellular Senescence May Explain the Inverse Correlation Between Cancer and Neurodegeneration
One of the more curious aspects of aging is that risk of Alzheimer’s disease and risk of cancer is inversely correlated. Why is this the case? Researchers here suggest that cellular senescence may be an important component of this relationship.
If cells in a given individual are more than averagely prone to becoming senescent in response to stress and damage, then this may lower the risk of cancer, as precancerous cells will be blocked from replication and removed by the immune system more efficiently. On the other hand, increased cellular senescence in the aging brain will more rapidly drive chronic inflammation and neurological dysfunction, leading to an increased risk of dementia.
Flies that Choose a Poor Diet Have a Shorter Lifespan than those Forced into a Poor Diet
This interesting study shows that when given the choice to consume sugar or protein, flies consume a lot of sugar and exhibit reduced life span as a result. Feeding the same proportional mix of sugar and protein to flies without giving them the choice of what to consume does not reduce life span to the same degree, however.
Prevalence of Ischemic Scars in the Retina Correlates with Heart Disease Risk
Researchers here note that the visible signs of vascular degeneration in the retina correlate with the risk of cardiovascular disease.
Immunoglobulin-M Antibodies Reduce Risk of Thrombosis by Binding to Extracellular Vesicles that Induce Coagulation
Researchers have in the past found that low levels of immunoglobulin-M antibodies correlate with an increased risk of thrombosis, the blockage of a blood vessel by, for example, fragments of a ruptured atherosclerotic plaque.
The Popular Science Media Fails to Distinguish Between Potentially High Yield and Probably Low Yield Treatments for Aging
It is of great importance to distinguish, where we can, between promising and poor approaches to the treatment of aging. If only poor approaches are developed, then we’ll age, suffer, and die on much the same schedule as our grandparents.
In the article here, metformin and senolytics are crammed together side by side, as though the same thing. They are very much not the same thing.
Raised Levels of Amyloid-? in the Retina Impair Lysosomal Function
Lysosomes recycle unwanted and damaged molecules in the cell, and are thus vital to cell health. Unfortunately, lysosomal function is progressively impaired with age.
Estimating that Technological Progress Accounts for Half of the Gains in Life Span Since the 1960s
Researchers here build an economic model of technological progress and its impact on human life span. The model suggests that advances in technology account for half of the gains in life span from the 1960s on.
Thoughts on Medical Progress and Living Longer
This article expresses sentiments regarding medical technology and human longevity that we’d all like to see more of in the mainstream media.
At some point, it will come to be seen by the average person as basically sensible to work towards minimizing the tide of suffering and death caused aging and age-related disease. It has been, in hindsight, a strange thing to live in a world in which most people were reflexively opposed to that goal.
Improving Autophagy to Restore Hematopoietic Function in Aged Individuals
Upregulation of LAMP2A is capable of improving the operation of chaperone-mediated autophagy in later life. A while back researchers demonstrated meaningfully improved liver function in mice via this mechanism.
Here, they start from the same point of LAMP2A and autophagy in order to try to address the age-related faltering of the hematopoietic system responsible for producing red blood cells and immune cells.
SPACs for Longevity Companies: Helpful or Not?
The present popularity of SPACs, special purpose acquisition companies, might be cynically thought of as being a sign that quantitative easing is catching up with us – there is too much money sloshing around in the system, all of it chasing too few opportunities for significant returns.
A SPAC is a publicly traded shell company that accepts investment prior to any specific idea as to what exactly the funds will be used for, sets a few famous people as figureheads to drum up interest, and then buys established companies or sizable stakes in established companies.
It is something of the reverse of the more traditional route to taking companies public. There will be SPACs for the longevity industry, because the longevity industry is a hot topic right now.
Mitochondrial Transplantation as a Treatment for Heart Disease
Mitochondria are the power plants of the cell, generating the chemical energy store molecule ATP. The function of mitochondria declines throughout the body with age, and this is particularly impactful in energy-hungry tissues such as the heart.
This decline appears to involve changes in mitochondrial shape and dynamics, as well as failing mitophagy, the quality control mechanism responsible for removing worn and damaged mitochondria.