Cellular mechanism to improve health span

6 min readApr 26, 2024

Abstract

As we age, we always look for signs of getting older, be it wrinkles on face, white hair or cracks on joints. The reality of life is we all grow old. What if we could fight this race against aging?

The starting point is to embrace the fact that chronological age is different from biological age.

What exactly is aging?

Aging can be defined as the time-related deterioration of the physiological functions necessary for survival and fertility(1). Although aging is different from lifestyle & chronic diseases, it is considered another disease which is going to plague us sooner or later.

While aging is a gradual decline in various physiological processes, there are a number of ways which can help us age healthily, which is defined by the ability of our cells to be healthy, to replicate & produce more cells. As we age, it becomes difficult for our cells to do these jobs. This condition is referred to as cellular senescence(2).

When we have cellular senescence, our cells become older & cannot keep up with normal wear & tear as well as fail to generate new cells. With cellular senescence, as a lot of worn out cells accrue, we begin to see signs of aging as described above in this blog.

Given the current healthcare pandemic, we are developing cellular aging well ahead of time. There are numerous trigger points which boils down to our nutrition & oral hygiene choices which could lead to reduced blood flow. chronic inflammation, oxidative stress & immune dysfunction.

However, we have seen a number of companies offering supplements with claims that they could reverse aging & promote longevity without understanding the mechanics of early aging for each individual.

To really drive our biology towards promoting healthy aging & longevity it is important to understand the biological processes at cellular level rather than falling for these fad supplements

The magic molecule- Nitric Oxide

Before we deep dive into mechanisms of cellular aging, it is important to understand what nitric oxide is. Nitric oxide is a signaling gas molecule that plays a key role in various biological processes including oxygen & nutrient delivery, is a vasodilator which means it causes blood vessels to relax, thereby regulating blood pressure, facilitating cellular communication, regulating insulin signaling, mitochondrial respiration & blood flow & more.

This magic molecule is produced via two pathways- ENOS & Nitrate- Nitrite 3 electron reduction pathway. We have discussed this in detail in our earlier blog. You could read about nitric oxide here

Briefly, ENOS- Endothelial Nitric Oxide synthase is coupled with Endothelial cells. This enzyme, in the presence of oxygen, converts L-arginine( a semi essential amino acid which our body produces) into Nitric Oxide & L-citrulline. However if eNOS is uncoupled due to inflammation, oxidative stress or oxidation of tetrahydrobiopterin(BH4), nitric oxide production is disrupted & it leads to a number of chronic health conditions.

The second pathway- nitrate- nitrite reduction via oral microbiome is more important since as we age our body’s ability to produce nitric oxide via endothelial cells is reduced by 10% every year. Microbes in the mouth could synthesize nitrate in green vegetables into nitrite which mixes with stomach acid to produce nitric oxide.

It has now been found that this magic molecule plays a key role in healthy aging & longevity.

Basics about human cells & its connection with healthy aging ( longevity)

Our body has around 38 trillion cells. Each cell has a cell membrane which has a certain amount of healthy fats, cholesterol, fatty acids, lipoprotein & more which maintains its structure & fluidity. Besides, living cells have mitochondria( energy power house or cells) & enzymes which consist of various proteins that facilitate biochemical reactions.

It is the mitochondria that provides energy to the cells & is considered to be an energy powerhouse. The structure & fluidity of cell membrane facilitates intracellular signaling & helps cells sense something outside of cells which helps them to perform various biological processes be in activating GLUT 4, producing Nitric oxide or improving mitochondrial biogenesis

This essentially means that healthy fats are key for regulation of cellular processes. It is no brainer that right nutrition choices are key to a healthy cell function. Consumption of bad fats such as seed oils or high sugary diets could alter the structure of cell membrane, thereby impacting intracellular signaling & rendering cells dysfunctional. This could make you age faster.

There are multiple factors at play that can drive healthy aging & improve longevity which includes

Telomere Length: Telomeres are protein structures found at both ends of the spectrum. Shortening of telomeres is an indicator of cellular senescence & cell depletion. As a normal function enzyme- telomerase keeps telomeres from wearing down. However as the cells divide, there is not enough telomerase, telomere length shortens resulting in cellular senescence & aging.High homocysteine levels accelerates the rate of endothelial cell senescence, establishing an association between atherosclerosis & endothelial cell senescence. Nitric oxide helps in delaying the cellular senescence & upregulates telomerase activity, thereby inhibiting telomere shortening. Nitric oxide also reduces oxidative stress, thereby further delaying cellular senescence. Research has also found a reversal relationship with periodontitis & telomere length shortening, further establishing the role of nitric oxide in healthy aging & longevity.
Mitochondrial biogenesis: Mitochondria is a powerhouse of cells, an energy furnace, an ATP cycle that rises to the occasion to deliver energy to cells to perform various tasks whenever there is a need- be it stress, inflammation or lack of nutrients. Through cellular communication, mitochondria can sense when we do not have enough energy, something called AMPK- ratio of AMP to ATP(adenosine triphosphate). When we use ATP, it goes down to ADP(adenosine diphosphate) & when cellular signaling is going on(everything is right), it again goes back to ATP. However when there is inflammation or oxidative stress going on, ADP further goes down to AMP(adenosine monophosphate).The other part of the mitochondrial story is the most important- mitochondrial biogenesis. This is a hallmark of healthy aging & longevity. Mitochondria need to be constantly recreating & reproducing itself. Master regulator of mitochondria is PGC-1 alpha which signals to mitochondria to actually deliver the energy at the time of need. It also signals to build more mitochondria. Having the right functionality of mitochondria is key to longevity. Raising the expression of PGC-1 alpha can do wonders for mitochondria biogenesis. There are multiple nutrition choices that could raise PGC-1 alpha levels which are deeply connected with functions of the oral & gut microbiome. Some of the food/food substrates which boosts mitochondria biogenesis include polyphenols, herbs, nightshade family foods, nicotine( I am not referring to smoking but foods having nicotine naturally- tomato, potato, egg plants), Ursolic Acid(peppermint, lavender, thyme, oregano, apple, cranberries), NMN(Broccoli, Cabbage, Mushroom, Avocado) & more. Which specific food/food substrates an individual’s biology needs depends upon functions of their oral & gut microbiome. However there is a catch. If our mitochondria is performing well, excess PGC-1 alpha activation could lead to production of reactive oxidative species (ROS) which could lead to oxidative stress, thereby damaging membranes of mitochondria & triggering mitochondrial dysfunction. Nitric oxide vis eNOS stimulates intracellular signaling & releases secondary messenger- Cyclic GMP which controls & boosts mitochondrial biogenesis.Therefore it is important to stimulate pathways that leads to not only optimal mitochondrial biogenesis but also right level of nitric oxide production
Inflammation: High level of chronic inflammation via gut microbiome or oral microbiome is said to upregulate production of cytokines , causing harm to various body organs & reducing our ability to heal & address infections, thereby impacting our biological age

Healthy Aging & Longevity is a function of multiple factors & standard OTC supplements such as NMN cannot be a standard solution. In order to attain improved health span & longevity, we need to look at multiple factors including functions of oral & gut microbiome, our endothelial cell’s ability to produce nitric oxide, optimize level of mitochondria biogenesis & level of oxidative stress

We at Genefitletics look at functions of gut & oral microbiome & provide precision nutrition interventions to boost nitric oxide production & tame down inflammation & oxidative stress for better longevity.

Citations

Cellular mechanism to improve health span

Written by Sushant Kumar