Athlete at Age

Scientists discover clues to what makes human muscle age

MAPK and Notch pathways apparently age human (and all other) muscle

Working in collaboration with Dr. Michael Kjaer and his research group at the Institute of Sports Medicine and Centre of Healthy Aging at the University of Copenhagen in Denmark, the UC Berkeley researchers compared samples of muscle tissue from nearly 30 healthy men who participated in an exercise physiology study. The young subjects ranged from age 21 to 24 and averaged 22.6 years of age, while the old study participants averaged 71.3 years, with a span of 68 to 74 years of age.

In experiments conducted by Dr. Charlotte Suetta, a post-doctoral researcher in Kjaer's lab, muscle biopsies were taken from the quadriceps of all the subjects at the beginning of the study. The men then had the leg from which the muscle tissue was taken immobilized in a cast for two weeks to simulate muscle atrophy. After the cast was removed, the study participants exercised with weights to regain muscle mass in their newly freed legs. Additional samples of muscle tissue for each subject were taken at three days and again at four weeks after cast removal, and then sent to UC Berkeley for analysis.

Morgan Carlson and Michael Conboy, researchers at UC Berkeley, found that before the legs were immobilized, the adult stem cells responsible for muscle repair and regeneration were only half as numerous in the old muscle as they were in young tissue. That difference increased even more during the exercise phase, with younger tissue having four times more regenerative cells that were actively repairing worn tissue compared with the old muscle, in which muscle stem cells remained inactive. The researchers also observed that old muscle showed signs of inflammatory response and scar formation during immobility and again four weeks after the cast was removed.

"Two weeks of immobilization only mildly affected young muscle, in terms of tissue maintenance and functionality, whereas old muscle began to atrophy and manifest signs of rapid tissue deterioration," said Carlson, the study's first author and a UC Berkeley post-doctoral scholar funded in part by CIRM. "The old muscle also didn't recover as well with exercise. This emphasizes the importance of older populations staying active because the evidence is that for their muscle, long periods of disuse may irrevocably worsen the stem cells' regenerative environment."

At the same time, the researchers warned that in the elderly, too rigorous an exercise program after immobility may also cause replacement of functional muscle by scarring and inflammation. "It's like a Catch-22," said Conboy.

The researchers further examined the response of the human muscle to biochemical signals. They learned from previous studies that adult muscle stem cells have a receptor called Notch, which triggers growth when activated. Those stem cells also have a receptor for the protein TGF-beta that, when excessively activated, sets off a chain reaction that ultimately inhibits a cell's ability to divide.

The researchers said that aging in mice is associated in part with the progressive decline of Notch and increased levels of TGF-beta, ultimately blocking the stem cells' capacity to effectively rebuild the body.

This study revealed that the same pathways are at play in human muscle, but also showed for the first time that mitogen-activated protein (MAP) kinase was an important positive regulator of Notch activity essential for human muscle repair, and that it was rendered inactive in old tissue. MAP kinase (MAPK) is familiar to developmental biologists since it is an important enzyme for organ formation in such diverse species as nematodes, fruit flies and mice.

For old human muscle, MAPK levels are low, so the Notch pathway is not activated and the stem cells no longer perform their muscle regeneration jobs properly, the researchers said.

When levels of MAPK were experimentally inhibited, young human muscle was no longer able to regenerate. The reverse was true when the researchers cultured old human muscle in a solution where activation of MAPK had been forced. In that case, the regenerative ability of the old muscle was significantly enhanced.

"The fact that this MAPK pathway has been conserved throughout evolution, from worms to flies to humans, shows that it is important," said Conboy. "Now we know that it plays a key role in regulation and aging of human tissue regeneration. In practical terms, we now know that to enhance regeneration of old human muscle and restore tissue health, we can either target the MAPK or the Notch pathways. The ultimate goal, of course, is to move this research toward clinical trials."

Overtraining - Maybe, Maybe not

The NY Times features an article today by Gina Kolata When Training Backfires: Hard Work That’s Too Hard.

The article describes a 15-year old runner who trains hard for a long period than experiences long term fatigue and degeneration of performance.

She attributes this, with some minor caveats, to over-training.  Maybe.  Maybe not.  Kolata provides no analysis of obvious variables that could also have affected the young athlete's (or ANY athlete's) condition: 

• No discussion of hormonal changes in a 15 year old?  When my stepson hit 15 he wanted to sleep 13 or 14 hours a day.  Then he grew almost 4 inches in one summer.  His body's resources obviously turned to growth.  Can a 15 year old expect to continue to make performance gains during such a period?

• No discussion of diet or nutrition.  What did the kid eat?  Did he change what he ate before his performance declined.  What about food or seasonal allergies?

• No discussion of hydration.

• No discussion of the kind of training regimen the runner followed or even his training goals.  This last point seem most important.  One can easily mistake ill considered training for over-training, especially when doing long single modality low-intensity training rather than short, varied, high-intensity training.

To her credit Kolata cites sources who see over-training as over-diagnosed.

Alpha^2

Survival analysis - What will kill you?

The Journal of the National Cancer Institute has a current article:

The Risk of Death by Age, Sex, and Smoking Status in the United States: Putting Health Risks in Context

From the abstract:

At all ages, the 10-year risk of death from all causes combined is higher for men than women. The effect of smoking on the chance of dying is similar to the effect of adding 5 to 10 years of age. For men who never smoked, heart disease death represents the single largest cause of death from age 50 on. For men who currently smoke, the chance of dying from lung cancer is of the same order of magnitude as the chance of dying from heart disease from age 60 on, and after age 50, it is 10 times greater than the chance of dying from prostate or colon cancer. For women who never smoked, the 10-year risks of death from breast cancer and heart disease are similar until age 60; from this age on, heart disease represents the single largest cause of death. For women who currently smoke, the chance of dying from heart disease or lung cancer exceeds the chance of dying from breast cancer from age 40 on.

It also has this great chart:

Alpha^2

Free "Real Age" assessment

Check out this "Real Age" assessment site.  RealAge.com prompts you to answer a broad range of questions on health, habits, relationships, diet, and fitness.  It then runs a proprietary algorithm to generate your real age relative to your calendar age.

While not a detailed as it as I'd like and a bit dated in its dietary assumptions, in 10 minutes it gives you a quick baseline, against which you can measure maybe once every 6 months.

I came in at:

56.3    Calendar age:
-12.4    Difference
43.9    Real age

A better assessment would include measures such as:

• Triglycerides
• Vitamin D levels
• Testosterone levels
• Free testosterone levels
• Body fat index

I'd like to see Ray Kurzweil and Terry Grossman do something like this or maybe CrossFit.  Maybe we should just do it here.  Hmmm?

Alpha^2

Quote for the day

"Everyone is entitled to his own opinion, but not to his own facts."

Daniel Patrick Moynihan

Killer carbs...key to overeating as we age

Australia's Monash University reports in it's newsline item titled "Killer carbs - Monash scientist finds the key to overeating as we age":

A Monash University scientist has discovered key appetite control cells in the human brain degenerate over time, causing increased hunger and potentially weight-gain as we grow older.

The research by Dr Zane Andrews, a neuroendocrinologist with Monash University's Department of Physiology, has been published in Nature. 

Dr Andrews found that appetite-suppressing cells are attacked by free radicals after eating and said the degeneration is more significant following meals rich in carbohydrates and sugars.

"The more carbs and sugars you eat, the more your appetite-control cells are damaged, and potentially you consume more," Dr Andrews said.

Dr Andrews said the attack on appetite suppressing cells creates a cellular imbalance between our need to eat and the message to the brain to stop eating.

"People in the age group of 25 to 50 are most at risk. The neurons that tell people in the crucial age range not to over-eat are being killed-off."

...

Dr Andrews said the reduction in the appetite-suppressing cells could be one explanation for the complex condition of adult-onset obesity.

"A diet rich in carbohydrate and sugar that has become more and more prevalent in modern societies over the last 20-30 years has placed so much strain on our bodies that it's leading to premature cell deterioration," Dr Andrews said.

Cholesterol and Testosterone levels

Ray Kurzweil and Terry Grossman, M.D. have 2 well-researched chapters, Hormones of Aging Hormones of Youth and Other Hormones of Youth: Sex Hormones in their 2004 book, Fantastic Voyage*, which provide a sound basis for a discussion of anabolic steroids and testosterone replacement therapy.  I take their work as a valuable introduction, because the science (as to the subject at hand) appears well within the consensus of serious peer reviewed medical research.

The first of the chapters defines anabolic and catabolic hormones.  Anabolic hormones facilitate or control tissue growth.  Catabolic hormones stimulate tissues to break down. The chapter has a simple chart, which illustrates how all steroid hormones in the body ultimately derive from cholesterol.  It looks something like this:

                          Cholesterol
                                  |
                         Pregnenolone
                         /                  \
                  DHEA                Progesterone 
                     |                  /            \  stress
                      Testosterone             Cortisol
                              |
                         Estradiol

This little flow chart of testosterone synthesis may only present a very simplified view of an enormously complex system, but it does establish an interesting relationship.  Our bodies synthesize testosterone from cholesterol.  Maybe not in every case, but for the most part higher cholesterol levels support higher testosterone levels.  Many of us at age have managed our diets and fitness regimens and taken supplements and even statins to lower cholesterol levels.  Doing so, likely, makes it more difficult for our bodies to maintain the higher testosterone levels, which enhance muscle growth, recovery, and repair. 

Alpha^2

_____________________________

* http://www.fantastic-voyage.net

Anamnestic response - Booster shots of exercise

Doug McGuff, MD posted a 1999 article on his Ultimate Exercise site which I believe merits revisiting. You'll need to click on his "Articles" link to the full text

Stasis Versus Dynamism Part III: Roadblocks at the Advanced Level and Blasphemous Experiments

McGuff (at least at the time) followed and contributed to high intensity training theory including Ken Hutchinson's, "Super Slow".  Time will judge the effectiveness of these protocols.  I've had some great success with them (although I consider myself a dedicated CrossFitter at this point).  Those discussions aside for now, I've always found McGuff's writing reasoned and honest.  He approaches the questions around exercise, fitness, and health with a deliberate and scientific methodology.

The last section of the article referenced above presents a very interesting idea,

The Ultimate Blasphemy, The Anamnestic Response

Several months ago I was discussing the Dose-Response relationship with Lance Reese, M.D. Lance is a friend that I met while in my emergency medicine residency who is probably one of the most brilliant people I have ever known. Lance is not a H.I.T. aficionado, he knows very little about the field. The combination of his brilliance and not having been indoctrinated makes him perfect to bounce ideas off of. Lance noted that the time course of the dose-response relationship suggested that the response was similar in behavior to immunologic responses. Further, recovery ability also seemed to be very much an immune phenomenon. Lance then suggested that there may be an anamnestic response to training that could be invoked with great potential benefit. I quickly dismissed this idea because it threatened my notion of the dose-response relationship and flew in the face of the H.I.T. [High Intensity Training] philosophy I had incorporated into my very identity.

An anamnestic response is a type of stimulus-response relationship that produces an exaggerated response from the organism. The anamnestic response is the basis for what are popularly called "booster shots". To bring about an anamnestic response you first introduce the stimulus to the organism. Next, when the organism begins to respond to the stimulus you reintroduce the stimulus at the point of the peak inflammatory response. What happens is the response (in the case of the booster shot) is increased dramatically. Lance suggested that reintroducing the same workout at the point of peak soreness (roughly 24-48 hours after the first workout) might increase the body's response. With immunizations there is a quick spike of antibody  that abruptly trails off to a sustained baseline. If you provide a booster stimulus during the antibody spike, an additional spike occurs on top of the first and then trails off to a much higher baseline. Having heard this argument, I promptly rejected it as a preposterous notion. The idea nagged at my subconscious for months.

At Ultimate Exercise we routinely tell our clients that if a workout makes them unbearably sore that they can come back the following day and repeat a submaximal workout in order to extinguish their soreness. We do not know why this works, but it certainly seems to. Recently I was working a long string of very busy shifts in the ER. In the midst of this, I found my self horrendously sore from the previous day's workout. On the way home from work I stopped by the facility and repeated my workout. I was astonished to find that the weights I had used the day previously felt ridiculously light. I decided to push close to the point of failure and managed to add 5-20 seconds on the previous day's TUL. Lance's discussion of the anamnestic response came rushing back to me. The following workout 9 days later proved to be a major blow-out. I broke out of my usual TUL [time under load] range with heavier weights.  I have repeated the anamnestic workout 4 times now, but now I use significantly more weight (usually about 40-60lbs more) and stop just short of failure.  My "regular workouts" are progressing nicely with 2-6lb jumps and stable TUL's. The "anamnestic" workouts are spectacular, with 10-20lb jumps on upper body and 20-40lb jumps on leg press. I am keeping about 9-10 days between the anamnestic workout and the next regular workout. We will begin trying this on other subjects. This is wildly experimental and I do not know if my results are atypical. We DO NOT advocate this as a protocol that works and we don't even recommend experimenting with it. If you do, however, please let us know how it is working. If anyone has other theories that might explain this phenomenon, we would love to hear them.

I wonder if some of the success of CrossFit protocols, which typically specify a cycle of 3 intense training days followed by 1 of rest might have inadvertently implemented an anamnestic pattern?

Alpha^2