Fountain of Youth

Doug McGuff, MD has an interesting new article, Fountain of Youth posted on his Ultimate Exercise site.

On May 23, 2007 a major stride in the quest for life extension occurred.  Researchers Simon Melov et al announced a treatment that successfully reversed aging. (www.plosone.org/article/fetchArticle.action?articleURI=info:doi/10.1371/journal.pone.0000465).   This reversal occurred not in worms, fish, or rats; but actually occurred in human subjects.  More importantly, this reversal was not simply a marker of aging, but an actual reversal toward normal youthful function at the genetic level.  The researchers tested 596 genes that appeared to be markers of declining function as a result of age.  Most of these genes were associated with mitochondrial function.  This is important for two reasons.  First, the mitochondria are the powerhouses for the cells of your body, they are the engine that makes us run.  Secondly, mitochondrial DNA is easier to study with greater certainty of accuracy because all of your mitochondrial DNA comes only from your mother.  As a consequence, differences in expression cannot be accounted for by the contribution of another person’s (i.e.-father’s) DNA that may react differently under experimental conditions.   The study definitively identified 179 genes that were reversed by the intervention, and  as the study stated “the transcriptional signature of aging was markedly reversed back to that of younger levels for most genes that were affected by both age and exercise”.   what was this miracle treatment?  The answer is STRENGTH TRAINING.  Strength training performed twice a week for a period of 26 weeks.  Even more amazing is that by standards of most people who participate in training facilities such as Ultimate Exercise, it was strength training that was done relatively poorly on substandard equipment.  The researchers had subjects perform leg press, chest press, leg extension, leg flexion, shoulder press, lat pull-down, calf raise, abdominal crunch and back extension for 3 sets of 10 reps, and arm flexion and arm extension for 1 set of 10 reps.  The equipment was Universal Gym, Inc. equipment.  Resistance was based on 50% of a 1 rep max and progressed to 80% of a 1 rep max.  Over the study period the subjects increased their strength by 50% which made them only 38% weaker than 25 year old cohorts.  

Further down in the article Doug connects these ideas with Arthur Devany's:

A New Definition of Aging  

What is interesting about this landmark article is the genes that were identified to be related to aging were genes that were largely involved in synthesizing enzymes of anaerobic metabolism or transporting anaerobic substrate for aerobic use.  What therefore appears to be a marker of youth, and consequently what gets lost with aging, is the ability to perform high-intensity anaerobic work.  This fits well with a concept proposed by Dr. Arthur Devany (www.arthurdevany.com) .  Dr. Devany is an economist who developed the concept of Evolutionary Fitness.  While I differ in specific details of his exercise recommendation, I believe his notions regarding diet, exercise and how they effect the expression of genes handed down to us by evolution are absolutely brilliant. The concept that Dr. Devany coined is Physiologic Headroom. Physiologic headroom is basically described as “the difference between the most you can do and the least you can do”.  Dr. Devany notes that when the difference between the most you can do and the least you can do becomes zero, you are dead.  Consequently, it is easy to extrapolate that the process whereby the most you can do and the least you can do decreases could be called aging.  What determines the most you can do is basically aneaerobic metabolism.  Anaerobic metabolism precedes aerobic metabolism and can cycle much more quickly. This makes sense from an evolutionary standpoint because anaerobic metabolism is much more primitive than aerobic metabolism which was a much later evolutionary development.  It therefore makes sense that aerobic metabolism requires substrate from the anaerobic metabolism to run.  Once the ability to deliver that substrate declines, aerobic metabolism must decline as well, and the amount of output that can be generated from any kind of exercise will approach zero.

Doug ties a lot of this to HIT and SuperSlow training and I give him tremendous credit as perhaps its most articulate and thoughtful proponent.  A bit further in the article he continues with:

If we embrace this concept of aging (the gap between maximal and minimal output), and the type of training that enhances this capability; then we must acknowledge that there is a type of exercise which can produce the opposite result.  Low intensity, steady state exercise will actually accelerate aging by this definition.  When exercise is of low intensity, the slow and intermediate fibers are called upon at a rate that does not result in fatigue and does not stimulate rapid cycling of anaerobic metabolic pathways.  As a result, anaerobic enzymes down-regulate and fast twitch fibers are never called upon.  An adaptive response then occurs whereby the fast twitch fibers are allowed to atrophy and die.  This is because, if they are never used in the face of this activity, they are simply dead weight which must be carried along.  While one may argue that this is an adaptation, we must remember that not all adaptations are beneficial.  In the process of losing our fast twitch fibers, we do not just lose physiologic headroom.  We begin to lose the largest glucose sink in our body.  Glucose is stored as glycogen (long chains of glucose strung together like a tinker-toy model).  About 70 grams of glycogen can be stored in the liver and 220 grams can be stored in the skeletal muscle.  The glycogen in the liver is used mainly to maintain a stable blood glucose level.  The glycogen stored in the muscle is used as emergency on-site fuel for bursts of high intensity muscular work.  The majority of the glucose stored in muscle is in the fast-twitch fibers, because that is where the fuel is needed for emergency anaerobic metabolism.  When we jettison these fast-twitch fibers, we set up a scenario for a rapid decline in metabolic health.  By losing the largest storage warehouse for glucose in our body, we begin to lose insulin sensitivity.  We already only have a storage capacity of 290 grams at baseline (which is way less carbohydrate than the average American consumes in a given day).  As we lose the glucose storing capability of these fast-twitch fibers, we have nowhere for our dietary glucose to be stored and glucose stacks up in the bloodstream.  The liver and muscles become completely full and decrease the number and sensitivity of their insulin receptors to protect themselves from excess glucose being transported into the cell (excess glucose binds to metabolic proteins and enzymes in a process called glycosylation—imagine pouring pancake syrup on your keyboard).  Glucose then begins to stack up in the blood which in turn stimulates the pancreas to make more insulin.  This creates a stimulus for continued decreases in muscle insulin sensitivity.  The body tries to protect itself by increasing insulin sensitivity in other areas, most notably your fat cells.  A circuitous metabolic process then occurs where excess glucose is circulated to the liver where it is converted to Triacylglycerol (triglycerides) and is circulated to the fat cells for assembly and storage.  The relative increase in glucose metabolism through aerobic pathways produces oxidative free radicals that produce inflammation and accelerate the aging process.  The details of all of this downstream metabolic mayhem will be the subject of future articles and are discussed in further detail (with supporting literature) in Body by Science. Interestingly, if you ever get yourself into this predicament and visit your doctor, you will be told to eat a high carbohydrate/low fat diet and to take up steady state activity.  If you are lucky, you may get started on meds that kill your testosterone production and produce weakness in what little muscle you still have left.  What will really turn around this metabolic process is high intensity strength training combined with a diet based on evolutionary principles.  

Another vote for strength training + paleo, and a warning about statins that "...kill your testosterone production...".  Well worth the read.

Alpha^2