Reading: Would You Like to Live to 150 Years Old?

Why Does Anyone Want to Live Beyond 100?

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 antiaging 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 overmedicalization 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 US. We seem culture-bound to buy any product or trend that promises to stop our telomeres from fraying or keep our gut microbiome from raising hell. We ponder antiaging advice from celebrities like Suzanne Somers, who 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Now, according to Sinclair, those theories of why we age prematurely are outdated.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

Sinclair’s new “theory of everything” is an information theory that supports the entire theme of Lifespan — that aging is a disease. Written with Matt LaPlante, the book gives credit to more than 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.

Here are the nine biochemical and physiological dysfunctions 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 proteostasis (protein maintenance)
6. Senescent cell accumulation (cells that don’t fully die off, wander around where they shouldn’t, and cause 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 health news detailed 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. Still, we want the bottom line and ask: What do I swallow?

But follow me for a moment.

Aging Breakthroughs at the Microscopic Level

Scientists just discovered a sort of “aging dance” of DNA loops, known as TADs (topologically associated domains). Scientists can now 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. They have figured out how to remove troubling, cancer-inducing methyl groups from chromosomes (hence the expression at Functional Medicine meetings, “If you’re a poor methylator, you might be a cancer-maker”). Very recently they became able to manipulate certain enzymes to reprogram the way our cells respond, with characteristic youthful markers instead of typical aging.

An example of these enzymes: 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, and then injected the virus into the mouse. Over time, the nerve grew back, restoring sight. Downright miraculous, declared Sinclair’s team. (We owe a lot to lab mice.)

Have I lost you yet?

Suffice it to say that the optic-nerve regeneration story in Sinclair’s book was the chapter that got me hooked. 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 in this book made me realize why it garnered the over-the-top endorsements.

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 (and maybe other mammals) have built-in longevity pathways that can be activated with either a molecule called NMN (nicotinamide mononucleotide), 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 cancers or heart disease at the same rate as others their age.

Sinclair’s personal regimen consists of a plant-based diet, no desserts, exercise, one gram of NMN, one gram of metformin, and assorted other supplements. He is careful to not make recommendations in his book, but he talks about putting his elderly father on this same protocol with good results. While anecdotal tales don’t make for good science, Sinclair hopes to conduct the first human clinical trial within a few years, not on extending lifespan, but on glaucoma.

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, consider the statement “take these supplements and your life will be longer.” Does that mean the opposite is true? Not taking these supplements will shorten your life?

The New Anti-Agers at the Cellular Level

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 sirtuins, 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.”

Should You Take one of the New Supplements? (NMN or NR: Which Supplement Makes Sense?)

The real powerhouse in the fight against the 9 Hallmarks of Aging — the one you and I can take part in right away — may be ingesting a dietary supplement that helps support NAD+ levels in your cells. NMN is expensive (about $80 a bottle online) and not always easy to find. NR has been patented and shows up in several products. I was sent a bottle of TRU Niagen®, 300 mg capsules, and I must say, I feel great on this stuff. (And I don’t usually notice the impact of dietary supplements.) It’s also been licensed to other supplement companies, like Life Extension, which offers a bottle of 100 mg capsules online.

The other things you can do are already well within your grasp. And I’m sorry to report that they all involve departing (briefly) from your cushy modern human life and acting more like an early Homo sapiens cave dweller. You’ve got to get uncomfortable. Step out of the civilized zone where we have evolved into extensions of our AI environments, with Echo-controlled thermostats and keystroke-delivered meals.

5 Things You Can Do Today to Increase Your Longevity

Here’s your homework to turn on your longevity genes:

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 overactivating 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 but it is. I found this one to be wildly unpopular among my women friends, who may all have compromised thyroids.
4. Exercise, of course. Adjust to high intensity interval training (HIIT). After a brief warm-up, 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®.

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, 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.