Live till 100?
Scientists Propose Living to 150 Years Old is Not Far Fetched Anymore
Living to 150 – just the idea of it struck me as not only impossible but undesirable. Why on earth would I want to live past 100, if the next 50 years were filled with disability and dementia? But the idea has tremendous appeal to David Sinclair, PhD, longevity researcher at Harvard and author of Lifespan: Why We Age and Why We Don’t Have To. When I discovered that many of my doctor and nurse friends were reading Sinclair’s bold vision of the future, I decided I had to see how this latest longevity book compared to the current rash of anti-aging ideas pitched today.
It was the endorsements that first grabbed my attention. Three pages of names – from Dean Ornish to Mark Hyman to Dale Bredesen--extolling Sinclair’s treatise as the last health book you’ll ever have to read, with comments like “stepping on the moon,” “a tour de force,” “the most important message of our time.” Wow. I was under the impression that a gentler, kinder zeitgeist had entered the cultural conversation with expert critiques of over-medicalization and appeals for comfort care over end-of-life heroics. What’s this renewed interest in living so long?
Aging has never been popular in the U.S. We seem culture-bound to buy any product or trend that promises to halt our telomeres from fraying or keep our gut microbiome from raising hell. We ponder anti-aging advice from celebrities like Suzanne Somers as she pushes bioidentical hormones.
From obsessive paleo diets to centenarians living in Blue Zones, I’ve been reporting the latest breakthroughs on the aging front for several decades. Remember Aubrey de Grey? The longevity researcher with the Rip van Winkle beard? He announced 20 years ago that his rejuvenation alternative would make him as old as Methuselah. Then when scientists discovered how pesky free radicals damaged DNA, inventor Ray Kurzweil started swallowing about 120 antioxidant supplements a day, giving rise to legions of tech-savvy biohackers.
Now, according to Sinclair, those theories of why we age prematurely are outdated. Antioxidants do indeed scavenge those pesky free radicals that damage chromosomes, but now it appears that free radicals also do some good. Basic science has moved forward.
A New Theory of Aging
His new “theory of everything” is an information theory that supports the entire theme of Lifespan—that aging is a disease. The book, written with Matt LaPlante, gives credit to over 60 international scientists who are each contributing a part of that information puzzle. Sinclair calls this collection of findings and extrapolated hypotheses the 9 Hallmarks of Aging. (see sidebar)
What Actually Makes Us Age?
Here are the 9 factors that when combined, make us “age”
1. Telomere attrition
2. Mitochondrial dysfunction
3. Stem cell exhaustion
4. Altered intracellular communication and production of inflammatory molecules
5. Loss of proteotosis (protein maintenance)
6. Senescent cell accumulation (cells that don’t fully die off, wander around where they shouldn’t, causing problems)
7. Deregulated nutrient sensing (decreased ability to monitor nutrients like sugar, lipids, amino acids)
8. Alterations to the epigenome (chemical compounds and proteins that can attach to DNA and direct such actions as turning genes on or off, controlling the production of proteins in particular cells)
9. Genetic instability (genetic mutations that interfere with repairing DNA, i.e., BRCA1 and BRCA2)
Now with groundbreaking but complex research findings at the nano level, it’s harder for the average health-conscious consumer to follow. With instantaneous genome mapping, and amazing CRISPR technology allowing scientists to replace one gene at a time, scientists can venture deeper into cellular mysteries. Researchers can monitor several new pathways of aging, like the mTOR pathway, which regulates how cells can be dormant (quiescence), or die off (senescence) or reactivate as stem cells. Scientists just discovered a sort of “aging dance” of DNA loops, known as TADs (Topologically Associated Domains). They have figured out how to remove troubling, cancer-inducing methyl groups off of chromosomes, (hence the expression at Functional Medicine meetings, “If you’re a poor methylator, you might be a cancer-maker”). Very recently they are able to manipulate certain enzymes to reprogram the way our cells respond with characteristic youthful markers instead of typical aging.
Have I lost you yet?
This is what it’s like plowing through Sinclair’s book – truckloads of scientific jargon and biochemistry. Finally, there was one chapter that had me hooked. One of Sinclair’s post-docs had a major breakthrough in longevity research when he crushed a mouse’s optic nerve, then injected three of the four enzymes (known as Yamanaka factors) into a virus, then injected the virus into the mouse, and witnessed over time, the nerve growing back, restoring sight. Downright miraculous, declared Sinclair’s team. (We owe a lot to lab mice.)
Optic nerves don’t just regenerate, but his lab managed to demonstrate that they can. Glaucoma and vision loss are serious conditions of aging eyeballs. Wading through the compilation of biochemistry is this book made me realize why it garnered the over-the-top endorsements.
Still, we want the bottom line and ask: Ok, but what can I do now?
Sinclair is careful to not make recommendations in his book but he talks about putting his elderly father on the same personal regimen with good results, namely: a plant-based diet, no desserts, exercise, one gram of NMN (nicotinamide mononucleotide), one gram of metformin and assorted other supplements. While anecdotal tales don’t make for good science, Sinclair hopes to conduct a first human clinical trial within a few years, not on extending lifespan, but on glaucoma.
Activating Your Longevity Pathways
Science has taken great strides into understanding new pathways of aging. Perhaps the most pertinent finding is that mice and humans (maybe other mammals) have built-in longevity pathways that we can be activated with either a molecule called NMN or NR, nicotinamide riboside.
Metformin, a prescription-only pharmaceutical drug prescribed for diabetes, also seems to favorably impact the built-in longevity pathways. Doctors have known for some time that patients on metformin don’t seem to get Alzheimer’s or certain cancer or heart disease at the same rate as others their age.
What makes good science?
The longevity mystery has just become more complex and the jury is still out as to whether this new cluster of information is actually extending life. In fact, Charles Brenner, PhD, the scientist who discovered NR, told me, “Sinclair is a great storyteller, but his hypothesis is not testable. He doesn’t have a falsifiable hypothesis.”
Science makes progress by working with falsifiable hypotheses—these are statements that have the capacity to be proven wrong, an essential feature of the scientific method. For example, the statement: take these supplements and your life will be longer. So does that mean that the opposite is true? Not taking these supplements will shorten your life? Uh, no, you can’t prove that so you can’t call it good science.
But that hasn’t stopped Sinclair or dozens of others excited about research on sirtuin, the family of proteins that regulate cellular health. There are seven types of sirtuins and at least four are known metabolic regulators that control gene expression. Sirtuins are to this decade what antioxidants were to the ‘90s—the latest darling in the quest for causal factors of aging.
Brenner discloses that he has a vested interest in the patented substance, nicotinamide riboside, commonly called NR. Both NR and the molecule that Sinclair takes, NMN, are precursors to a fundamentally important molecule, nicotinamide adenine dinucleotide
(in its oxidized form abbreviated NAD+), which is in every cell of your body, but starts to decline at about age 40 or 50, depending on how deleterious your lifestyle is (i.e., sun damage, chemo/radiotherapy, poor diet, sedentary).
Brenner has other problems with Sinclair’s ideas. Promoting wide scale use of metformin does not strike him as sound. “If people are looking to age better, we know that high levels of physical activity, mental and social engagement are positively associated with wellness. We have recently learned that metformin blunts improvements in physical fitness due to exercise. My reading of the literature says that healthy people should not take metformin.”
Brenner also warns that “we don’t know what’s in some of the NMN capsules going around. We know for a fact there’s a company with an NAD-boosting product that adds caffeine, nicotinamide, and Vit C, and perhaps unknown contaminates. The caffeine alone might account for why people report feeling energized.” Others contain ingredients that may boost cholesterol levels. “The only supplements people should take are ones with proven safety trials from clean, inspected labs.”
5 Things That May Increase Your Longevity
1. Fast Intermittently. – Try to be a little hungry each day. Stop any late-night snacking. Then go from your dinnertime to eating a late lunch— skipping breakfast. Aim for 12 hours of fasting to start. Stretch to 16, or try two days a week with 500 calories or less.
2. Eat a primarily plant-based diet. Cutting back on meat means that you are lowering the amount of amino acids, which your body recognizes as hunger, creating slight starvation. This is all about not over-activating the mTOR pathway. If it’s overactive, you’re at greater risk for heart disease, Alzheimer’s, and certain cancers.
3. Give up your thermonuclear comforts. Try to be shivering cold at least once a day. Scientists don’t fully understand why being cold is linked with turning on longevity pathways. I found this one to be wildly unpopular among my women friends, who may all have compromised thyroids.
4. Exercise, of course. Adjust it to high intensity interval training (HIIT). After a brief warmup, force your heart rate to climb as you fully exert for 30 seconds, then recover back to near-resting levels for 90 seconds. Repeat 6 to 8 cycles. This will take less than 15 minutes, 2–3 times a week.
5. Boost your NAD levels with a proven nicotinamide riboside, such as Niagen, or NMN.
So that’s the good news. We alter the epigenome and thus, genetic expression, according to Sinclair, when we shiver, are hungry, and move a lot. Contemporary life is not so great for us, since it dampens this long-life genetic activity.
Really? I can hear my epidemiology colleagues saying, “ridiculous.” The strides in public health, sanitation, clean water, agricultural and protein production, infection control, vaccination, first responder networks, have all extended the average lifespan, primarily by reducing infant mortality.
This leads me to conclude that for us health-conscious folks who have a pretty good life and want to be around to enjoy it fully without disability, dementia or despair, these lifestyle adjustments might be worth the discomfort. Aging with grace, dignity and a youthful spirit – that seems to be a personal choice, no matter what you swallow.
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