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If you look at all of the chronic “killer” diseases—heart disease, cancer, diabetes, chronic lung disease—they don’t start actually early in life. They start increasing dramatically in the middle age.

Prevalence of Chronic Diseases vs. Aging

Anti-aging researchers have noticed this. The folks involved with the TAME (Targeting Aging with Metformin) study and the gerontologists from different parts of the world all saw the same thing. It’s not just one disease that’s killing us. It’s all of them. Something is going on, and it’s coming to all our body cells. Aging is happening at a cellular level, and our body is getting some breakdown. 

David Sinclair

Meet Dr. David Sinclair, a famous anti-aging researcher.

David Sinclair

Sinclair is a tenured faculty at Harvard. He was born in Australia, educated at the University of New South Wales, came to the US to get a Ph.D. at Harvard, did some postdoc work on the aging of yeast. He uncovered the power of a chemical called resveratrol. Sinclair also worked on proteins called sirtuins as well as NAD+ (nicotinamide adenine dinucleotide). He and his team also discovered NMN (nicotinamide mononucleotide). Check this video which highlights several of Sinclair’s works, discoveries, and other involvements. 

Resveratrol, sirtuins, NAD+, NMN—remember these terms as we go along. We’ll describe each of them and their connections with aging. 

Resveratrol

Have you heard people talking about red wine being good for your heart? While the link between red wine and fewer heart attacks hasn’t been completely understood, researchers are pointing to resveratrol, a chemical found in the skin of red grapes. 

Resveratrol is a polyphenol, a type of plant compound. While abundant in the skin of red grapes, resveratrol can also be found in peanuts and some berries. It somewhat acts like an antioxidant, perhaps preventing damage that may lead to cancer, heart disease, Alzheimer’s, diabetes, and other chronic diseases. 

How resveratrol produces such effects isn’t fully realized yet, though studies pointed out the link between resveratrol and the activation of genes that make SIRT1. (We’ll talk about SIRT1 in the next section)

If resveratrol is good for the heart, why are we not hearing much about it? That’s because to get enough benefits from resveratrol, you’d need to drink a hundred glasses of red wine per day. Most research has been done on animals and in vitro using high quantities of resveratrol. Also, human studies were limited and focused on supplements where concentrations are way higher than natural resveratrol in red wine. 

Sirtuins

Sirtuins are a family of proteins found in almost all organisms. These enzymes either stimulate or repress the expression of other enzymes that have to do with metabolism and aging. In mammals, there are 7 known sirtuins in mammals: SIRT1 to SIRT7. (Sir2, the yeast sirtuin that Dr. Sinclair worked on while doing his postdoc work in MIT, is analogous to the mammalian SIRT1.)

Human Sirtuins

Why talk about sirtuins (particularly about SIRT1)? As I mentioned in the last section, resveratrol’s health effects have been linked with the SIRT1 gene. Activating the SIRT1 gene has been shown to boost mitochondrial activity and kicks off various processes that counter the effects of obesity, age-related decline, and age-related diseases. 

It’s also worth mentioning that sirtuins stimulate autophagy. Autophagy is when the cell takes up worn-out cellular components (like old, used proteins) then burn them. Autophagy inhibits inflammation; inflammation (along with our cellular metabolism) is a key component of aging. 

Sirtuins’ activity is also an epigenetic process—it doesn’t change the genes, but it changes the spools on which the genes wound on. This is how it deregulates some inflammatory processes. 

NAD+ and NADH

NAD (nicotinamide adenine dinucleotide) is a coenzyme found in all living cells and exists in 2 forms: the oxidized NAD+ and the reduced NADH. 

If you remember the metabolic process of the Krebs cycle from your biology classes, there’s a high chance you’ve heard of NAD+ and NADH. We won’t go into much detail, but during metabolism: 

  • NAD+ picks up an electron to become NADH. 
  • NADH donates an electron to become NAD+. 

This continuous give-and-take of electrons generates energy used to power various biological processes. 

Unfortunately, NAD+ levels decline with age. Sirtuins (which are enzymes) depend on NAD+ (which are coenzymes) to function. If there are only a few NAD+, sirtuins’ activity would then be limited. Sirtuins appear to protect cells from age-related decline, so limiting their activity would push forward the adverse effects of the aging process.

Connecting the dots

Are there other ways to activate human sirtuins? Fortunately, yes. 

One, fasting or calorie restriction. When we fast, we can increase sirtuins’ activity as well as autophagy. 

Two, resveratrol. Resveratrol has the potency to activate SIRT1, mimicking the good effects of fasting, and preventing the effects of obesity and age-related decline. However, I already mentioned that resveratrol has to be taken in huge amounts to be helpful. 

Three, NMN (nicotinamide mononucleotide). Related to resveratrol, NMN is supposedly a much better form of resveratrol. It’s an NAD+ precursor and booster. As people age, they could maintain healthy levels of NAD+ by taking NMN supplements. 

As you can see, Sinclair’s work on aging, yeasts, sirtuins, resveratrol, and NMN are all interconnected, looking to stop—even reverse—aging. You can watch this video to learn more about what we discussed in this article. 

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