Do you really want to live forever and ever?

 (Published in ENRICH magazine, 2022)

THE GOD WE CALL SCIENCE continues to prise open previously locked doors that hold the secrets to our living far longer and healthier lives, and to eventually reversing the aging process -- miraculous as this might sound.

Over the past two decades, a plethora of research studies into the cellular and molecular bases of aging has revealed a variety of techniques, both simple and esoteric, that will allow us to add healthy years to our lives.

As a consequence, the quest to attain a longer "healthspan," otherwise called "healthy aging," has replaced the current goal of increasing one's lifespan but submitting to the many geriatric diseases that make longevity a pain to endure. Alzheimer's, arthritis, diabetes and loss of eyesight are among a range of degenerative and communicable diseases that curse the elderly amongst us.

Now, however, reaching the "oldest-old" age of 90 is no longer wishful thinking with new longevity extending technologies such as "epigenetic rejuvenation," and "hyperbaric oxygen therapy." But if living to be 180 years-old or much older isn't your cup of organic green tea, you might soon be able to choose to reverse your age and become a real-life Benjamin Button, but absent the sad ending.

"Soon" might come as early as 20 years from now. This vision of radical life extension and an on-demand "Fountain of Youth" should become options available to us.

It must be mentioned the longest lived person on record is the French supercentenarian, Jeanne Calment, who was on this Earth for 122 years and 164 days. She was born in 1875 and died in 1997. A devout Roman Catholic, Calment loved chocolates, oranges and bananas and exercised regularly. She also smoked at least one cigarette a day and almost daily drank a glass of port wine.

One longevity devotee predicted longevity technology was advancing so rapidly that "most people will have access, and quite affordable access, to life extension technology." This forecast made in 2021 by multimillionaire Dmitry Kaminskiy, who spends lavishly on longevity research, is quite too optimistic but does reveal the exciting state of current anti-aging technologies.

Filipinos should benefit from the life extension technologies being developed in the United States and other affluent countries such as Australia, Spain and Israel -- if and when these become affordable. Decades hence, these technologies might conceivably boost the life expectancy at birth in our country, which in 2021 stood at 71.4 years on average for men and women. Pinays live far longer than their men. They will survive, on average, to reach 75 years old compared to the Filipino male's 67 years old. This data does not, however, include the deleterious effect on longevity inflicted by COVID-19.

Think about it. Old but not infirm. Older but not "old" in the traditional sense of that word. Or as Hollywood icon Clint Eastwood (now 92 years old) aptly put it: "Aging can be fun if you lay back and enjoy it.”

Grandparents and the promise of immortality that is their grandchildren.

Less is good

The easiest way to live longer is to eat less. Yes, it's that simple. Eat less. Living longer by eating less is one of the claims made by people that champion methods such as intermittent fasting and the ketonic or keto diet.

Longevity researchers said eating less, also called calorie or caloric restriction (CR), might add at least five more healthy years to your life if doggedly pursued. CR has even been proclaimed by some commentators as the closest we can get to a real Fountain of Youth.

One can extend his lifespan by combining CR with exercise, access to competent medical care, a good diet (think Mediterranean diet), and avoiding vices such as smoking. Drugs and therapies currently under development might eventually add 10 to 15 more years to the average life while also boosting healthspan.

"There is plenty of evidence that calorie restriction can reduce your risks for many common diseases including cancer, diabetes and heart disease," said Dr. Edward Weiss PhD, a scientist from Saint Louis University in Missouri, back in 2008. "And you may live to be substantially older." His research has since been backed-up by other studies that came to the same conclusion.

New research over the past few years studying CR among humans indicates calorie-restricted diets can indeed slow down the aging process and increase longevity.

A study involving only 34 people and published in the peer-reviewed scientific journal, Cell Metabolism, in 2018 found that limiting calorie intake by 15% over two years can slow aging and protect against diseases such as Alzheimer’s, cancer and diabetes.

These people shed 5% or more of their body weight with much of this loss being fat. Also, they saw lower insulin levels and lower nighttime core body temperature. These outcomes are two key biomarkers of aging. 

Research involving mice show that cutting calories by 20% to 40% significantly extended the lives of these animals, which are regarded as good analogs to humans in clinical trials. A study released in 2006 found that mice eating 8% less and exercising a bit more over their lifespan reduced and even reversed aging-related cell and organ damage. Evidence that CR boosts lifespan in rodents is unquestionable, according to some longevity scientists.

"Our research provides evidence that calorie restriction does work in humans like it has been shown to work in animals," said Dr. Weiss. "The next step is to determine if this, in fact, slows age-related tissue deterioration. The only way to be certain, though, is to do a long-term study."

Scientists still don't know exactly why CR slows down the aging process. There is this theory CR lowers our metabolic rate and causes the body to generate fewer "free radicals," which are unstable atoms that cause aging and can damage cells. Free radicals are also implicated in a host of other diseases while damaging our arteries and, surprisingly, shrinking our brains.

CR decreases levels of "triiodothyronine" (T3), a thyroid hormone, and by so doing slows metabolism and tissue aging. It's not sufficiently clear if reducing T3 levels through CR does slow down the aging process, however. Scientists said a slowed metabolism is linked to longer lives in hundreds of animal species since it allows the more efficient use of energy.

How much calories should we restrict? In 2013, Dr. Anthony Leachon, who was then a consultant with the Department of Health, recommended a daily calorie intake for Filipino women of 1,500 calories and 2,000 calories for men. He said Filipinos should try to consume not more than 500 calories per meal.

This means consuming one cup of rice (200 calories), 100 calories of protein each of meat or fish, a serving of fruit equal to 50 calories and 50 calories of vegetables.

“If eating pork or beef, take only small portions,” noted Dr. Leachon, who has since risen to prominence as an expert on COVID-19.

While there are no DOH guidelines about CR, an American study published in 2018 defined CR as eliminating anywhere from 15% to 18% of total recommended daily calories. In this regard, we must be aware that Americans have a higher recommended daily calorie intake compared to Filipinos.

American women likely need from 1,600 and 2,400 calories daily while men require 2,000 to 3,000, according to the 2015-2020 Dietary Guidelines for Americans.

Using these guidelines and applying it to Filipinos means Pinays should do away with 225 calories per meal while men should consume 360 fewer calories. Forgoing that cup of rice (200 calories) is the easiest way to start on CR.

The amount of calories you lose will depend on your age, overall health, height, weight, lifestyle and activity level, among other factors. It will, therefore, be wise to consult with a doctor before going on a calorie-restricted diet, especially if you're a senior citizen.

The downside to CR is it takes just too long and might harm your health if you're not careful. Many health experts agree a person might add 4.5 years to his life by eating 15% less starting at the age of 25, said Dr. Eric Ravussin, a professor of human physiology and director of the Nutritional Obesity Research Center at Pennington Biomedical Research Center in Louisiana. That's a really tough challenge most people can’t tackle..

Caloric restriction

Evolutionary biologist Dr. Jay Phelan PhD from the University of California, Los Angeles estimated that "40 years of caloric restriction would give a three to seven percent increase in longevity, so an optimistic estimate would be an additional four years or so."

Dr. Phelan in 2005 also said mice will live longer if their diet is restricted by 10%. Restricting their diet by 20% will make mice live even longer. "But restrict their intake by 60% and they starve to death," he warned.

There is also the danger that regularly eating fewer calories than your body needs might show down your metabolism and lead to muscle loss. Severely restricting calories can lead to fatigue. Also, maintaining calorie restrictions too long might lead to nutrient deficiencies.

The promise of youth

Sometime this year, if things go as planned, SOCOM, or the U.S. Special Operations Forces Command, will conduct clinical trials of an oral anti-aging drug. These historic trials will involve a pill with the potential to “delay aging” and “prevent onset of injury.”

SOCOM described the pill as a “first-in-class nicotinamide adenine dinucleotide, oxidized state (NAD+) enhancer.” NAD+ is a coenzyme central to metabolism and is a key molecule in preserving health and metabolic function. The anti-aging pill SOCOM will test contains health-enhancing food additives that boost NAD+ levels.

NAD+ helps slow down aging by lengthening our telomeres, which are the protective caps at the end of our DNA. In doing so, it reverses age-related damage at the cellular level. NAD+ also removes toxic free radicals from our bodies.

But SOCOM, whose job is to kill people, isn't interested in making their Special Forces operators live to a ripe old age despite their lethal profession. What interests SOCOM “is enhancing the mission readiness of our forces by improving performance characteristics that typically decline with age.”

SOCOM expects the trials will ultimately lead to the development of a drug that might see "improved human performance -- like increased endurance and faster recovery from injury.” In other words, SOCOM wants a drug that will enable its warriors to endure pain longer while healing faster from battlefield wounds. Think super soldier.

Telomere

Epigenetic rejuvenation

For the rest of the world, the value of the SOCOM-sponsored clinical trials is the anti-aging part of this project. The importance of the SOCOM trials is not lost on longevity scientists such as Dr. David Sinclair, a professor of genetics at Harvard Medical School and author of the bestseller, "Lifespan: Why We Age -- and Why We Don't Have To," published in 2019. This groundbreaking book details his research findings (some of them controversial) on the biological processes that cause aging.

Dr. Sinclair, a leading authority on longevity, makes the argument that “Aging is a disease, and that disease is treatable.” He sees aging as the single greatest risk factor for heart disease, cancer, diabetes, dementia, and many other diseases of age.

His incredible goal is to extend lifespan to 150 years by the end of the century. But his most astonishing claim is that natural death will eventually become a rarity. Sinclair sees a future world where we’ll be able to get vaccines and boosters that reverse aging and cheat death.

Dr. Sinclair asserts the “epigenome is reason why we age” because cells lose their identity. This is why “we grow hair in our ears,” he said. Asked if we can slow down aging or reset the aging process, his answer was emphatic: “I believe this is possible.”

The Australian biologist also says that “to reverse aging -- eat less often” since eating less turns on longevity pathways. He admits to practicing intermittent fasting, which might also be called a form of calorie restriction.

He's strongly interested in NMN or nicotinamide mononucleotide. Some studies have shown NMN has astounding beneficial effects that counter normal aging. NMN boosts NAD+ levels and is a crucial cofactor involved in over 400 metabolic reactions in cells.

Dr. Sinclair said he takes one gram of NMN daily plus resveratrol, metformin and aspirin, apparently with no adverse effects. He noted that NMN, which he calls a defense against aging, stabilizes the epigenome and turns on a longevity pathway. He's also a vocal champion of epigenetic rejuvenation, a most controversial aspect of longevity science.

Dr. David Sinclair. He is 53 years-old.

A scientific paper on epigenetic rejuvenation published in 2012 defines this therapy as "reprogramming the age of a cell in isolation while maintaining its differentiated state, thus effectively rejuvenating the specialized functions peculiar to that cell type."

Since then, scientists have discovered it’s feasible to partially reverse aging.  The biotechnologies in question hinge on altering our "epigenome," or the molecular machinery that determines which of our genes are switched on or off. As we grow old, our epigenome becomes dysregulated or unbalanced. This epigenetic dysregulation has been identified as one of the causes of aging.

The answer to moderating epigenetic dysregulation is epigenetic reprogramming. This technology makes it possible to reprogram, or change, a dysregulated, old epigenome into a younger state.

Making cells younger means upregulating four specific "Yamanaka factors" in a cyclical way, but not continuously. Yamanaka factors are proteins that can reprogram differentiated cells (or non-stem cells) by changing the epigenome. In his laboratory, Sinclair discovered we can reset our biological age by using the Yamanaka factors.

This partial cellular reprogramming involves applying Yamanaka factors (Oct4, Sox2, Klf4 and cMyc ) to cells long enough to reverse cellular aging and repair tissues. This has to take place without cells returning to pluripotency, or the capability of a cell to differentiate into one of many cell types.

Clinical trials have shown upregulating the Yamanaka factors for a short time made animal cells younger while reducing or undoing many other aging symptoms. The groundbreaking discovery that mature cells can be converted into stem cells was made by Japanese geneticist Shinya Yamanaka, and led to his being conferred the Nobel Prize for Physiology or Medicine in 2012.

The startling progress being made in developing therapies such as cellular reprogramming that promise to not only extend our lives but to also reverse human aging might also bring with it the danger of developing cancer. Epigenetic rejuvenation has been successful in mice, but only in mice thus far. No trials have been conducted with humans.

In March 2022, scientists at the Salk Institute for Biological Studies in California and American biotech firm Genentech, Inc released a paper claiming they safely and effectively reversed the aging process in middle-aged and elderly mice by partially resetting their cells to more youthful states.

"We are elated that we can use this approach across the life span to slow down aging in normal animals. The technique is both safe and effective in mice," said Dr. Juan Carlos Izpisua Belmonte, co-corresponding author who is a professor in Salk's Gene Expression Laboratory, and one of the pioneers in aging research.

The study saw Belmonte, a Spaniard, and his colleagues test variations of the cellular rejuvenation approach in healthy mice as they aged. A goal of the study was to establish the safety of the approach over a longer time span.

His laboratory in 2016 reported for the first time they’d used the Yamanaka factors to counter the signs of aging and increase life span in mice with a premature aging disease.

Promoting the well-being of elderly Filipinos