January 28th 2019

 

Longevity - How do we maximize it??? 

The fountain of youth? The perfect diet? What is it? 

Since the days of Greek and Roman philosophers or the naturalists Darwin and Lamarck, humans have thought about the changes that occur within mammalian species as they attempt to adapt to the ever changing environment and live as long as possible as well as furthering the species through successful procreation. 

Longevity is on the minds of many of us, me especially. Fears of a ruined society or early demise are always swirling in the news with global temperature alterations and sea levels rise, polluted waterways or our air, dysfunctional governments not serving the people, etc... Little of this is controllable by us at the base level.

I really try to avoid the news. I prefer to stay positive and make personal choices daily that benefit others and my family.  

What is truly controllable is our personal behavior and activity. For the purposes of this article, we will focus on the longevity genes known as sirtuins. 

All mammals have cassettes of genes with the sole purpose of dealing with extremes of all environmental inputs. Some genes encode for stress proteins like the class of temperature shock proteins, heat and cold shock proteins. Others encode for adrenal gland cortisol receptors to handle differential psychological and physical stress. Further yet, are groups that encode for receptors that sense any physical perturbations.

Sirtuins are a master set of 7 genes that regulate the activity of a series of other genes, enzymes and proteins meant to keep us alive and virile. Dr. David Sinclair and Dr. Peter Attia have a phenomenal high end discussion on the Podcast "DRIVE" that can be found on iTunes from 2018. 

The discovery of the sirtuin class of genes in the 1990's lead to an explosion of research over the past three decades into their function in human health. 

What is clear is that these genes are heavily involved in DNA repair, mitochondrial cellular energy production and biogenesis, macronutrient metabolism, inflammation dampening, oxidation reduction, increased insulin secretion, clearance of damages cells, telomere DNA tail maintenance and much more. To put it simply, sirtuins are involved in the most important pathways for human survival. 

What we are now learning is that certain lifestyle activities can activate or suppress these genes for our benefit or detriment: (some of these are still theoretical)

Activation and thus benefit:

1) Fasting - potentially intermittent (12-16 hours per day) and prolonged (more than 24 hours)

2) Heat stress

3) Restriction of calories or low protein states potentially via mTOR, the master metabolic switch

4) Exercise and movement

5) Resveratrol chemical found in the rind of a red grape

6) Polyphenol chemicals in some vegetables and fruits

Or conversely-

Dampening or detrimental:

1) Over eating or caloric excess (biggest problem)

2) Sedentary behavior (second)

3) Euthermic environments, i.e. lack of extremes in temperature

4) Bacterial infections/dybiosis via lipopolysaccharide molecules


The most controllable factor here is to avoid overeating. This is likely the most dangerous event that we perform repeatedly as Americans. We bombard our GI tract with millions of molecules daily that are metabolically aging us faster than our genes expected. Think of a diabetic person as a canary in a coal mine. The advanced aging of a human that has chronically excessive levels of glucose on board is a wakeup call for all of us to heed. 

Taken all together, we see a picture of humans having the ability to change there life expectancy based on some basic lifestyle principles. 

When we look at it from this perspective of longevity, this new research shows us that repair mechanisms are turned on more favorably when the body is acutely stressed by exercise, heat, caloric restriction and potentially other similar environmental inputs but worsened by chronic behaviors of laziness, overeating and mental stress. 

In my mind, the profound benefit of this sirtiun adaptation is that the mammalian physiology shifts towards a repair and growth state during these periods of fasting and re-feeding that historically occurred.  

Just like the Blue Zones and many other studies of disease and lifestyle, we have the ability to eat less, move more, love more, stress less, and choose long life over a shortened sick ending. 

In the esteemed words of Michael Pollan, "Eat food, not too much, mostly plants". 

Dr. M  

Sirtuin Chapter Science Direct Weblink

Peter Attia David Sinclair Shownotes 

Sinclair Nature Reviews Molecular Cell Biology Article

Guarente NEJM Article

Sitruin Graphic in Cell Science

LPS and SIRT Diagram

Dang Drug Discovery Today Technol Article