Longevity and the medical fight against aging

Since the dawn of human philosophy, we have accepted two profound truths: there is a slow but perpetual decline in one’s vitality after young adulthood and this decline ultimately culminates in a singular ending of death.  This realization has pervaded our history.

In 400 B.C., Hippocrates’ theory of aging proposed that each person had a finite quantity of innate heat (aka vitality) that is spent at a unique rate over their life. According to Hippocrates, this vital force could be replenished, but never fully, thus the reserve always diminishes until death.  

Death resulted from a complete diminishment of this vital force and his advice for longevity was moderation and the maintenance of daily activities. Although our modern medical theory of aging replaces the idea of loss of innate heat with persistent stress induced metabolic decline, the idea is the same. Both theories propose that vitality is a depreciating asset even in those who focus on a healthy diet, exercise and a lifestyle of moderation.  

With our current knowledge, we can definitely slow the aging ‘current’ with supplements, nutrition and positive lifestyle choices, but as Hippocrates theorized greater than 2000 years ago, there is nothing we can do currently to get back upstream.

So what is the benefit of aging? 

If natural selection is the driving force in our physical design, why are our lifespans so short in comparison to other organisms like Giant Tortoises and greenland sharks which often live to be greater than 150 years old.  Why wouldn’t natural selection preferentially chose the longevity genes and have us live and procreate for 100’s of years. Well, the answer is complex. First, you must consider that during modern man’s existence, a high majority of us died of infection and injuries before aging took its toll.  Therefore, even if natural selection favored longevity, up until the middle of the last century, there wouldn’t have been any true realization of this benefit. Secondly, it would take a lot of evolutionary ‘energy’ to evolve skeletons, organs and soft tissue that would be strongly resistant to infection, trauma and stress.  As most things follow the path of least resistance, evolution chose to have us procreate early and often, leaving the later half of our lives as ancillary and usurped by the vitality of our own youth. But with modernization, this equation has changed. Currently, 70% of the world population dies from age related conditions and only 8% die from accidents and trauma.  This is a complete reversal and now our scientific community is pondering wehther they can bioengineer ourselves off of our current evolutionary path and onto another path which would aggrandize longevity.

So why do we age?

The good news is that we currently have a strong understanding of human physiology and how our genetic blueprint governs and regulates our living system.  The bad news is that even with this knowledge, we are not significantly closer to creating a compendious explanation for why we age. To put it simply, the process is so complex and multi variant, that we are still defining the parts, not the whole.  I recently read a good journal article that gives a comprehensive summary of the known factors that lead to human aging.  This topic is also well covered by SingularityHub, the website created by the X Prize founder Peter Diamandis MD.  Below, I have also included a brief description of these factors and we have also listed some useful approaches to hopefully counteract these factors and slow the aging process.

1. Instability of our genetic code: Time does not always heal all wounds. For example, seemingly benign but genome damaging activities like flying in an airplane, sun exposure, dental x rays and urban living to name a few, continually expose us to physical, chemical and biological insults that damage our DNA. It is the accumulation of this damage overtime, that contributes to the aging process.  
   
   DNA damage accumulation diseases: Werner and Bloom syndrome
   Tx: Avoid insults and consider NAD+/NMN/NR/VitB3/Nicotinamide 

2. Shortening of our telomeres: The ends of DNA strands in mammals are capped and protected by telomeres, which are short pieces of DNA that are repeated many times in a row. Telomeres are analogous to the plastic cap on the end of a show string that keep it from unraveling. It is these structures that help protect our DNA from damage over our life span.  Telomeres shorten every time a cell divides and mammals are unfortunately not able to easily produce more. With time and after many cycles of cell division, telomere exhaustion occurs. This loss of your telomeres is strongly linked to aging and certain diseases.
   
   Telomere exhaustion diseases: Pulmonary FIbrosis, Aplastic Anemia
   TX: Stress and weight management, PARP/ATM Kinase

3. Epigenetic alterations: Overtime , DNA damage in humans is a given.  To repair this damage and avoid mutations, the 2 strands of DNA must unzip and allow for the repair work to be completed.  After the DNA is repaired the DNA zips back together and forms a complex 3D structure. After many cycles of DNA repair, these 3-D structures can change permanently.  Once this change occurs, it can change the way our DNA is expressed, which is associated with the signs and symptoms of aging.
   
   Epigenetic alteration diseases: Heart disease, obesity, cancer
   TX: Avoid DNA damaging activities, Sirtuin activators like NMD/NAD

4. Loss of proteostasis: Proteostasis, by definition, refers to a balanced state of protein production.  As almost every biological pathway in the body relies on proteins to function, any disruption can be devastating. Aging is associated with a gradual break down in proteostasis, both with the quantity and quality of the proteins being produced.  
   
   Proteostasis disruption diseases:  Alzheimer's disease
   Tx: Nutritional support, rapamycin and proteostasis supplements 

5. Deregulated nutrient-sensing: One of the biggest reasons that we lose energy when we age has to do with age related changes in our ability to sense nutrient and energy levels in our body.  For example, the kinase triad is a group of enzymatic pathways that help the body achieve maximum efficiency with metabolism. These pathways, consisting of AMPK, mTOR and UC,  become less efficient and dysregulated overtime. This, as with disruption of the ICF-I and II pathways, can result in inefficient metabolism and decreased energy for cleaning house functions like autophagy and DNA repair.
   
   Deregulated nutrient sensing diseases:  most chronic aging diseases
   Tx: Intermittent fasting, resveratrol, NAD/NMN, Metformin 

6. Mitochondrial dysfunction: Mitochondria are the small but powerful structures in our human cells that are the primary site for energy production.  Primarily through oxidative phosphorylation, the mitochondria produce the fuel, Adenosine Triphosphate (ATP), that our body needs to run.  With age, the ability for our mitochondria to function at a high level diminishes along with the production of ATP. This is correlated with loss of energy and performance that is seen universally with aging and it has also been associated with age related chronic illnesses.
   
   Diseases of mitochondrial dysfunction:    Muscular Dystrophy, ALS
   Tx: Nutritional support, Resveratrol and SERT activators        

7. Cellular senescence: As cells age, they can become problematic, stop dividing and even be disruptive. This is defined as cellular senescence. High levels of cellular senescence is associated with a chronic inflammatory state.   And if these cells are unable to be removed, commonly through a recycling process called autophagy, this chronic inflammatory state will lead to aging and disease.
   
   Diseases of cellular senescence: Cardiovascular disease, cancer
   Tx: Intermittent fasting, Rapamycin

8. Stem cell exhaustion: It is well understood that stem cell exhaustion is a driving force in the development of age related diseases.  As we age, there is a huge reduction in functional stem cells in our body thus leaving us ill equipped to deal with things like injury and damage from chronic inflammatory states.  
   
   Stem cell exhaustion disease:  Diabetes, neurodegenerative diseases
   Tx: Stem cell therapies 

We are just at the start of this race to extend human longevity.  Although the answers are currently eluding us, we are making meaningful strides for the future. If you find this topic interesting, check out episode 50 of our podcast, Beauty and the Surgeon.

In this episode, Amy and I discuss some of the critical hurdles that the medical and nutritional community now faces as we try to increase human longevity. We also offer some real solutions that you can implement in you life right now.  Also, keep checking back to this blog over the next year as we will be delving further into this topic.