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Musings (Periods of Reflection or Thought.) About Living An Extra-Long Life

Some 14 years ago I ventured to Harvard Medical School to interview Harvard Professor David Sinclair, who became the pied piper of anti-aging pills with his published discoveries involving the red wine molecule resveratrol. I ended up writing a book THE ANTI-AGING PILL (now a rare book at Amazon) and was confronted by an unexpected fact: most people don’t want to achieve super-longevity. They would rather retain a youthful appearance over living long enough to drool at the mouth, need to wear diapers to handle their incontinence and be drugged into mindlessness. This is what modern medicine has made of old, old age. As someone once said to me: “What people want is thick hair, smooth skin and Viagra baby!” I ended up re-titling my book to THE RED WINE PILL, which was more appealing.

How long do you want to live?

In answering the question, “How long do I want to live,” it took me a while to realize the answer to that question is rooted in the quality rather than the quantity of life (healthspan over lifespan). The obvious answer to that question is: “As long as I am healthy.”

Chronic disease has been engineered

The problem is that food producers and the medical establishment have engineered foods and medicines to get people to overeat and to chronically need medicines to allay the symptoms of diets laden with fructose corn syrup or a hormone altering molecule called bisphenol A. America has a high-calorie malnutrition problem. Fixing that would be bad for the food and medicine business.

The public can’t imagine they have been gamed for more disease. Just when a naïve and unsuspecting population figures this out is unknown. The Food Pyramid developed by public health authorities has been abandoned as a misdirection that led consumers away from essential fats and towards carbohydrates and sweeteners that produced humans who can’t stop eating (leptin resistance – leptin being the hormone that tells the brain we have had enough to eat.) Public health authorities are remiss in fully alerting the public to the misdirection.

Until stevia replaces fructose corn syrup and artificial sweeteners and people back away from carbohydrates (bread, pasta, cereal, white rice), and until the public’s misdirected phobia over fats and cholesterol is abandoned, the diabesity epidemic will continue. (Americans were eating butter, lard and other fats in the 1960s and early 1970s and were mostly lean bodied.)

And as you will learn below, this metabolic epidemic may remain in effect for decades even after dietary changes are made.

So your grandfather lived to 100. Will you?

Now all longevity seekers are reading a news headline that is a bit disturbing. If you’ve been bragging that you expect to live long because your grandfather lived 100 years you may have to rethink that idea. It turns out a newly published study reveals genetics has little impact on longevity. (Actually, epigenetics controls aging, explained below.)

A study involving data obtained from 400 million people suggests longevity is mostly determined by lifestyle and environment (epigenetic changes). Heritability only explains ~7% of longevity.

The study, published in the journal GENETICS, strongly suggests pedigree has little to do with longevity while selection of a spouse may be an overwhelming factor. You might live as long as your grandfather, but you would only achieve that if you ate the same food and drank the same water and got the same amount of sunshine as he did.

Do you really want to know what maladies lay ahead?

Modern technology is certainly going to confront all of us with information we may not want to hear. There is now a test that can detect Alzheimer’s disease six years before symptoms appear. Another test can predict macular degeneration that robs people of their central vision at least 4 years before there are any detectable changes in the eyes. But gosh, what to do about these predictive tests if there is no remedy at hand? These kinds of predictive tests may only lead to dismay and despair. Why go on living, some senior adults may ask?

Your mate is your longevity factor

Did you ever notice how two genetically unrelated people get married and soon develop the same body shape? Genes have a dynamic aspect called epigenetics. The food we eat (or don’t eat), the water we drink, the radiation (solar) we are exposed to, alters the proteins that gene manufacture. If men are the traditional breadwinners and their female spouses the bread makers, and diet is a key factor in longevity, then it reasons that selection of a mate may be all encompassing.

Genetically delayed disease

However, I recently wrote a report showing that early in life events, even in the womb, may produce delayed consequences (by many decades) or even generational consequences (grandchildren will be affected by something they were not exposed to but their grandparents were.

People exposed to fructose corn syrup, or a hormonal altering chemical called bisphenol A, or exposed to antibiotics in early infancy, have been reprogrammed epigenetically and are prone to develop high blood pressure, obesity and diabetes later in life.

In animal studies mega-dose resveratrol and quercetin, components of some anti-aging pills, help re-program the genes involved in these maladies but theses doses are impractical in humans and early human studies have been disappointing in this regard. More studies need to be done.

More choices of anti-aging pills

Since 2004 when resveratrol pills became widely available (now 531 brands being marketed) a number of other longevity pills have come to the public’s attention.

One is metformin, a ten-cent anti-diabetic pill that some experts in the field of aging want to employ in a $50 million study that would likely increase the human lifespan by about 8%.

Another is an MTOR (target of rapamycin) autoimmune drug that requires a doctor’s prescription and has resonated with longevity seekers just yet.

NAD BOOSTERS

The most recent anti-aging pill to debut is a coenzyme of niacin. Niacin is a precursor for NAD (nicotinamide adenine dinucleotide), required for cell energy. NAD is required for activation of that same primary gene targeted by resveratrol, the Sirtuin1 survival gene (more about resveratrol and NAD in a moment).

NAD levels decline with advancing age.

Findings from pilot studies measuring NAD+ plasma levels
Healthy Americans
Age	NAD+ Plasma Levels
20-40 years	50-60 mcg/mL
41-60 years	36-39 mcg/mL
> 60 years	4-8 mcg/mL
Unhealthy Americans
Age	NAD+ Plasma Levels
72-80 years	under 1 mcg/mL

The non-flushing version of niacin, niacinamide (nicotinamide) that is provided in most multivitamins has failed to prevent or delay the onset of diabetes and so researchers began to explore other ways to boost NAD levels. Designer niacin derivatives were developed – natural precursors for NAD such as nicotinamide riboside and nicotinamide mononucleotide. A question is, if these advanced forms of niacin are better absorbed and more biologically available, why are they supplied in such large (100-250+ milligram doses)?

Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) have been shown to raise NAD levels in humans. But a key issue is whether they get to the hypothalamus in the brain as this is where governance of food intake takes place via NAD. While nicotinamide riboside does raise NAD levels in humans a newly published report shows nicotinamide riboside, one of the new designer niacin molecules being commercialized, simply doesn’t get past the blood brain barrier. But to add to the perplexity of this topic, animal studies do show NR is effectively transported to the hypothalamus in the brain. The method of delivery of NR may have facilitated passage through the liver however. This topic becomes very complex and difficult to sort out. NR does/doesn’t pass the blood/brain barrier?

A 300 mg dose of nicotinamide riboside is reported to increase optimal NAD+ blood levels by 2.7 fold. The large dose may be due to the inability of NR to gain passage through the liver and difficulty passing through the blood brain barrier.

Very large doses of nicotinamide riboside are being employed when NR is postulated to be a more bioavailable molecule, which suggests less nor more would be needed.

Tryptophan and NAD

Tryptophan, that amino acid dietary supplement that was suddenly yanked from the market in 1989 when a pharmaceutical company “mistakenly” produced a toxic form that had to be recalled, also converts to NAD. No wonder it was taken from the marketplace. As time went by its anti-aging properties would have become apparent. Tryptophan would have been the first anti-aging pill before all the others. Tryptophan had been sold for 15 years before recall by the FDA.

Tryptophan supplements have returned to the marketplace, are safe to take, but it does take a couple of grams of tryptophan to convert to meaningful amounts of NAD in the body. About 60 mg of tryptophan is said to produce ~1 mg NAD. Thirty (30) to thirty-five (35) milligrams of NAD internally converted from 2000 mg tryptophan would be about right for adults.

In contrast to large doses of nicotinamide riboside, gram doses of tryptophan or a few hundred milligrams of niacin-based derivatives, a very low dose of resveratrol was found to dramatically increase NAD levels in lab animals.

Until the questions over passage through the blood brain barrier and dosage are sorted out, a simpler and more economical approach would be to take tryptophan supplements. Tryptophan has added benefits as it converts to serotonin, a brain chemical that facilitates sleep and boosts mood.

NAD is so essential for cell energy there are two dietary sources that generate it. Nature utilizes niacin and tryptophan, two ubiquitous molecules in foodstuffs, to convert to NAD. Wine is a third dietary source of NAD boosters via resveratrol, though a bottle of wine provides only 1-2 milligrams of resveratrol. Because cells ravenously need to make energy, turnover of NAD is rapid, but instead of being disposed of it is 85% salvaged and recycled 2.4 times a day. Which is why humans need niacin replenishment every day. Because of a decline in NAD levels with advancing age, the diet may not provide enough niacin to boost NAD. Dietary supplements may be in order.

If employing tryptophan supplements, vitamin B6 should accompany tryptophan to facilitate its conversion to NAD. A couple of grams (2000 mg) of tryptophan + vitamin B6 would be appropriate for adults. Be aware, tryptophan slowly converts to NAD whereas resveratrol and niacin produce a more immediate effect.

Recall, when resveratrol was first posed as an anti-aging pill in 2004 it was heralded as a Sirtuin1 survival gene activator; niacin is a Sirtuin1 gene silencer. So I wouldn’t take both resveratrol and tryptophan at the same time. Also, tryptophan is not a substitute for niacin in the diet or in a supplement regimen.