A new article just published in Circulation, Time and the Metrics of Aging, does a great job of the opportunities we have to head off functional aging. This is the core of what our service is set up to achieve.
biological aging takes many years before it finally translates into the deterioration of physical and cognitive function. This opportunity for prevention should be eagerly embraced because this has extraordinary translational potential.1
The suggestion is that by working to reduce exposures to things that contribute to Biological Aging, described in the article not as counting birthdays but “the changes that occur with aging at the molecular, cellular, and intercellular levels”, we may be able to delay the onset of Functional Aging (“the age-associated decline in physical, cognitive, emotional, and social functions that may be either so subtle as to be evident only under challenge or so severe that they curtail performance of basic activities of daily living and contribute to loss of independence”).
Delaying Biological Aging
To me, this is where most of our efforts should be focused on in health care. Currently, people mostly seek care when a function is lost, ie they get to the point where daily activities are compromised.
The basic hallmarks of biological aging were described in a landmark article published in 2013 by Fernando Lopez-Otin and include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication.
Some deeper terminology in there but let’s focus on two areas:
- mitochondrial dysfunction / epigenetic alterations
- Mitochondria are the primary source of cellular energy.
- They communicate to the nucleus and it’s DNA, impacting epigenetic presentation
- Are sensitive to oxidative stress
- Are the primary point of dysfunction in most cancers
- mitochondria very dynamic and can be made new and improved by our actions and influencing our environment
- Nutrient Sensing/Cellular senescence
- These are two areas impacted by something called mTOR.
- mTOR is essentially a growth signal and if it is always on, signals aren’t generated to trigger autophagy (cellular recycling) so we get a population of senescent cells (underperforming)
- mTOR also is involved in nutrient sensing impacting how we utilize nutrients at the cellular level.
- mTOR is very dynamic and can be controlled by our actions
While biological aging involves factoring in the number of birthdays, the good news is that age does NOT have to be the primary determinant role in biological aging.
To continue through this analysis we have here we must first define what phenotypic aging is referring to;
The term “phenotype” refers to the observable physical properties of an organism; these include the organism’s appearance, development, and behavior. An organism’s phenotype is determined by its genotype, which is the set of genes the organism carries, as well as by environmental influences upon these genes. Due to the influence of environmental factors, organisms with identical genotypes, such as identical twins, ultimately express nonidentical phenotypes because each organism encounters unique environmental influences as it develops.2
Essentially, the phenotype is the how cells are acting or presenting pursuant to the environment and associated stress to which we are subjected.
Biological Age->Phenotypic Age
Putting these two areas together:
This is another terrific representation of how we can impact our cellular aging. The body is always experiencing a yin-yang type of scenario. We aren’t looking to eliminate stressors all together, as there are powerful actions in the resilience mechanisms, but we certainly can look to exert control over certain stressors to keep a healthful balance. If we achieve that, it seems we can keep the phenotypic age at a lower level.
Functional Aging The Key to Longevity
One of the most succinct explanations longevity I have seen is by Peter Attia, MD.
I was explaining the relationship between lifespan (x-axis) and healthspan (y-axis) to one of my patients. My goal is to move the black line to the blue one. Live longer (more x-axis) and live better (altered shape of decline curve).
The basic premise is that it isn’t that hard with modern medicine to live longer, as evidenced by increasing lifespans 4, but we don’t want to end up with a low quality of life in the nursing home.
Altering the graph in the referenced study (admittedly not very skillfully), we can visualize our mission:
Our mission is to reduce biological aging by methods that we can exert influence over. This then will reduce the resultant phenotypic and functional aging presented. Translation: a little work now to increase the time spent feeling and functioning in an optimal manner, while decreasing the portion of our life spent in the red end stages.
No two people are the same, but there are a common set of things we can look at together to identify a prioritized set of actions to be considered with the purpose of decreasing biological aging and increasing healthspan. No matter where you are on the birthday count, or where you are on the functional aging chart, there are a host of interventions that can be considered. The BEST time to consider this is in the green or yellow areas, but there are upsides for orange and red as well.
Mitochondria can be influenced by a host of factors. Diet, environment, toxins, light, and much more clue mitochondria into how they are to perform. Part of this performance is signaling to the nucleus of the cell, which is how we get the epigenetic manifestations. More and more of these interactions between the mitochondria and nucleus are being defined, this is one that I saw just this month “The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress”5. This just confirms that if we can exert some strategic control over metabolic stress (note I didn’t say avoidance) we can actually signal different genetic manifestations. Does this cause a little bit of a second thought with the “you are your genes” dogma?
While the mitochondria and other things like environment can influence genetic expression, your hard-coded genes play a role as well. One way, called out in the article, is methylation:
Predictable changes in DNA methylation—a fundamental epigenetic mechanism—track chronological age in humans, as well as phenotypic changes that occur during the lifespan and predict risk of incident coronary artery disease and cardiovascular mortality, as well as a wide range of adverse outcomes.
Methylations is a very involved chain of events that influence how our genes are turned on or off. One of the key steps in methylation is a gene called MTHFR, which is involved in folate metabolism (which then continues on in the methylation process). There have been some estimates that 50% have an inherited mutation in this gene that decreases its effectiveness. My experience after testing many people is that a vast majority (I have only seen one with a wild-type/normal MTHFR gene) have some deficiency in the MTHFR gene. Just knowing this can have a huge impact on food and supplement choices. One easy way is folic acid avoidance, as that makes folate metabolism more challenging, as has been highlighted here previously.
Growth Signaling via mTOR
What mode our cells are in on the growth vs rest/recovery paradigm is subject largely to diet and activity levels. I have scratched the surface on this previously, but insulin and protein trigger mTOR which kicks in growth signaling. Further, if we continue throwing high volumes of nutrients into he body consistently mTOR also has a role in down-regulating the cells sensitivity to those nutrients. This 30,000-foot view leads to why intermittent fasting and macronutrient variances come in to play as tools.
This article did a great job, especially graphically, in helping to show where and how we can impact cellular aging. This is a powerful thought to learn we can exert much influence over our how we age and in many cases more so than birthdays and genes. While this is an active landscape on the research front, there are some established, safe, well-tolerated tools we can work together to deploy on your quest to a longer healthspan. This is the core mission of our service.
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