Longevity: How May Science Make Us Centenarians?

By the virtue of scientists' hard work in the field of biology and human health, now we have a life expectancy twice as long as our ancestors. The ongoing studies and investments in the field of longevity bring us closer to living 100 and beyond.

Data from the Centers for Disease Control and Prevention (CDC) shows how life expectancy increased among ethnicities living in the US. According to this demographic research, life expectancy is now 30 years longer, ranging from 80 to 85 years, compared to that of the 1900s. This improvement in human longevity is largely attributed to the advancement of the healthcare system and emerging biotechnological strategies.

How does longevity depend on DNA and genes?

One of the latest groundbreaking discoveries in the field of longevity over the last two decades is Yamanaka Factors. These are 4 genes involved in the process called cellular reprogramming - turning old cells into stem cells or “age 0”. Using these 4 Yamanaka Factors, Harvard University Professor David Sinclair and his Lab achieved the Benjamin Button effect, rejuvenating old mice’s vision and restoring a youthful appearance.

Human longevity and healthspan are dependent on numerous factors such as diseases and age-related disorders, and epigenetics. The latter is what makes us unique, and shows how environmental factors change our healthy gene expression without changing DNA itself.

Imagine our DNA as the old CDs/DVDs and the diseases as the scratches. While we age, many harmful factors accumulate scratches on our DNA. Consequently, DNA damage results in mutations and accelerates aging, hence, inhibiting the important information for longevity gene expression.

The studies in epigenetics help to acquire valuable knowledge on how to slow down aging and enhance healthspan through non-medical interventions. One of these interventions is the activation of longevity genes.

According to the GenAge database, there are more than 300 longevity genes in humans, the most studied of which are the Sirtuins family of 7 proteins (SIRT1-7), FOXO3, PARP1, mTOR, IGF-1, SOD2, and others. Scientists are adamant that by “activating” healthy genes and “deactivating” the harmful ones, it may be possible to prolong the human lifespan.

However, due to DNA deterioration with age, the activity of these genes declines. But the study led by Chuks Kenneth Odoh et al, once again shows that the component known as nicotinamide adenine dinucleotide (NAD+), a critical molecule in all living forms, has a central role in regulating metabolism, energy generation, gene expression, and DNA repair. The upregulation of the longevity molecule NAD+ has the potential in prolonging the human lifespan.

How does NAD+ prolong healthspan?

NAD+ stands for nicotinamide adenine dinucleotide. It was first discovered in 1906 when pellagra was widespread. The main cause of this disease was the lack of proper levels of Vitamin B3s (also known as Niacin) and NAD+ in the human body. Later, this small molecule was associated with longevity and the prevention of DNA mutations. However, longevity gene activity consumes most of the NAD supplies. And by middle age the human body is left with depleted NAD+ levels, hence, less protected DNA and numerous aging disorders.

As an example, the PARP1 longevity gene is responsible for neuroprotection and has a central role in DNA repair. However, every time this gene gets activated in response to DNA damage, it consumes NAD. Another longevity gene receiving the most attention is Sirtuins, especially SIRT1 and SIRT6.SIRT1 is responsible for caloric restriction, prevention of inflammation, and even the onset of cancer. SIRT6 participates in metabolic regulatory and DNA repair processes while increasing mammalian lifespan by up to 30%.

A recent study demonstrated how the overexpression of the SIRT6 gene may increase the lifespan in mice and other mammals. So, the same effects may be applied to people as mice are one of the biologically closest animals to humans.

But, all of these processes require energy, in other words, proper levels of NAD+. Yet, its levels decline with age. Hence, with reduced levels, the protective processes may be delayed or even stopped for good.

Assume the human body as a car. Mitochondria, small organelles producing energy for numerous cell functions may be the engine. But this engine needs fuel to propel the “car”. And here comes NAD+ which will be the fuel. As the fuel starts running out, the “car” starts breaking down.

How to increase the NAD+ levels?

Longevity molecules, also known as “youth molecules” may be great candidates for enhancing NAD+ levels and reactivating healthy genes. They are called NAD+ precursors or booster molecules and the most researched of them are NR and NMN. These molecules are also the safest of all the other NAD precursors.

NR is an abbreviation for nicotinamide riboside and it is a molecule that turns into NAD+ via numerous chemical processes. The study accomplished by the Nestlé Institute of Health Sciences demonstrates how NR inhibits age-related diseases by boosting NAD content. This molecule has been available in the form of a supplement since 2003. Although NR is a promising precursor, it takes two steps to convert into NAD+. This in its turn consumes more energy and time. An alternative and a closer-to-NAD molecule is NMN (nicotinamide mononucleotide) which takes one step to boost NAD+.

NMN molecules are also available as powder, gel, tablets, and encapsulated supplements. A study carried out by Efferpharm, Shanghai evaluated the health impacts of NMN supplements in humans. 66 healthy individuals aged 40 - 65 took part in this trial and made up 2 groups - NMN and placebo groups. The trial was designed with two stages.

After 30 days, the study scientists noted an 11.3% increase in NAD+ levels. Noteworthy are the results at the end of the trial when the NMN group demonstrated a 38% NAD+ rise, while the placebo group came out with no changes.

According to the trial, the above-mentioned Sirtuin genes get activated thanks to NAD+ enhancement through NMN supplementation. The clinical trial once again stressed the importance of activating these genes for DNA repair and a longer healthspan.

Although NMN supplements are effective enough alone, their health implications may be doubled if used with other longevity vitamins such as TMG, Vitamin B12, Resveratrol, and Folate. You can obtain each supplement separately or with a 5-in-1 NMN capsule formula.

One such formula supplement manufacturer conducted a liposomal NMN case study. As a result of a 1-month NMN consumption, the study participants documented a 5,56% increase in NAD+ levels. The case study tracked the dynamics of other longevity genes that also showed a positive increase after NMN supplementation.