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  Latest update: 3/13/2024

Staying Healthy - the role of exercise.

BE ACTIVE, STAY HEALTHY - a commentary by Erin Digitale

Regular running slows the effects of aging, according to a new study from the Stanford University School of Medicine that has tracked 500 older runners for more than 20 years. Elderly runners have fewer disabilities, a longer span of active life and are half as likely as aging non runners to die early deaths, the research found.

The study has a very pro-exercise message," said James Fries, MD, an emeritus professor of medicine at the medical school and the study's senior author. "If you had to pick one thing to make people healthier as they age, it would be aerobic exercise. "The new findings appear in the Aug. 11 issue of the Archives of Internal Medicine.

When Fries and his team began this research in 1984, many scientists thought vigorous exercise would do older folks more harm than good. Some feared the long-term effect of the then new jogging craze would be floods of orthopedic injuries, with older runners permanently hobbled by their exercise habit. Fries had a different hypothesis: he thought regular exercise would extend high quality, disability free life. Keeping the body moving, he speculated, wouldn't necessarily extend longevity, but it would compress the period at the end of life when people couldn't carry out daily tasks on their own. That idea came to be known as 'the compression of morbidity theory."

Fries' team began tracking 538 runners over age 50, comparing them to a similar group of non runners. The subjects, now in their 70s and 80s, have answered yearly questionnaires about their ability to perform everyday activities such as walking, dressing and grooming, getting out of a chair and gripping objects. The researchers have used national death records to learn which participants died, and why. Nineteen years into the study, 34 percent of the non runners had died, compared to only 15 percent of the runners.

At the beginning of the study, the runners ran an average of about four hours a week. After 21 years, their running time declined to an average of 76 minutes per week, but they were still seeing health benefits from running. On average both groups in the study became more disabled after 21 years of aging, but for runners the onset of disability started later.

"Runners' initial disability was 16 years later than non runners," Fries said. "By and large, the runners have stayed healthy." Not only did running delay disability, but the gap between runners' and non runners' abilities got bigger with time. "We did not expect this," Fries said, noting that the increasing gap between the groups has been apparent for several years now. "The health benefits of exercise are greater than we thought."

Fries was surprised the gap between runners and non runners continues to widen even as his subjects entered their ninth decade of life. The effect was probably due to runners' greater lean body mass and healthier habits in general, he said. "We don't think this effect can go on forever," Fries added. "We know that deaths come one to a customer. Eventually we will have a 100 percent mortality rate in both groups."

But so far, the effect of running on delaying death has also been more dramatic than the scientists expected. Not surprisingly, running has slowed cardiovascular deaths. However, it has also been associated with fewer early deaths from cancer, neurological disease, infections and other causes. And the dire injury predictions other scientists made for runners have fallen completely flat. Fries and his colleagues published a companion paper in the August issue of the American Journal of Preventive Medicine showing running was not associated with greater rates of osteoarthritis in their elderly runners. Runners also do not require more total knee replacements than non runners, Fries said.

"Running straight ahead without pain is not harmful," he said, adding that running seems safer for the joints than high impact sports such as football, or unnatural motions like standing en pointe in ballet. "When we first began, there was skepticism about our ideas," Fries said. "Now, many other findings go in the same direction." Fries, 69, takes his own advice on aging: he's an accomplished runner, mountaineer and outdoor adventurer.


The benefits of a plant based diet can be magnified by adopting the strategy of Time Restricted Eating (TRE). This article reviews the concept and speculates as to why it is a healthier way to eat.

A few of the highlights for me:

  1. It is better to eat the majority of your calories before 3 PM in the afternoon.

    "The TRE intervention by Sutton et al. revealed hyperinsulinemia was reduced when daily eating was completed by 1500 h, but such a strict eating protocol is not likely to be practical or socially acceptable at a population level. Studies of "late" TRE, or when total energy intake was restricted to meals consumed after 1600 h, have resulted in impaired fasting glucose, lowered glucose tolerance, and increased ratings of hunger."

  2. If you are already exercising regularly, adding TRE would appear to add minimal additional health benefits. I suspect this is even more so if you eat the majority of your calories in the middle of the day.

    "However, we propose that for most "healthy" individuals, adding TRE to a program of regular physical activity would impart minimal additive effects on a range of health-related outcomes."

If you have decided to make changes in your daily routine to improve your long term health, and want to pick a place to start - diet changes versus adding regular exercise to your daily routine - exercise gets the nod.

"We believe that exercise training undertaken in accordance with national and international guidelines imparts greater whole-body and tissue-specific metabolic health benefits than any current dietary intervention. " But of course these two interventions are not mutually exclusive. Most of us already exercise regularly. But after doing some reading on the pros and cons of TRE, I've also chosen to move the bulk of my calories to midday and skip an early breakfast (other than my coffee). I also avoid carbohydrates as much as possible for my evening meal, going heavy on salads and vegetables. I'm not sure I will be any healthier in the long run, but I can say I feel much more comfortable after my dinners these days.

For more on TRE.


Two interesting papers.

First, from the American Journal of Cardiology. 5000 men followed up to 50 years. Those in the top 5% of cardiovascular fitness lived almost 5 years longer than those in the lowest 5 percent.

We often "hear" that you can "injure" your heart by exercising too much. This study also puts that idea to rest.

In a second, group of 191 Swedish women, 38-60 years of age in 1968, were given an ergometer cycling test. When their mental status was evaluated in 2010 (forty years later), it was found that the women with high physical fitness at middle age were nearly 90% less likely to have developed dementia compared with the women who were only moderately fit.


Numerous studies have documented a decrease in cancer risk of 10 - 20 % in physically active individuals, and as much as a 50% decrease for certain selected cancers. A recent study from Sweden focusing on prostate cancer found a 35% decrease in the study subjects who were physically fit. A definite positive for male cyclists.


The following is form a post on the CPTIPS Facebook page.

When you think about the health benefits of exercise the usual association is with improving or maintaining your cardiovascular health. But its impact on your metabolic health may be equally as important in disease prevention.

This article suggests that a successful weight loss program can correlate with a "re-setting" of your body's cell sensitivity to the effects of the hormone insulin e important in carbohydrate metabolism. The medical literature supports the beneficial effects of exercise on carbohydrate metabolism, not only by its direct, insulin independent movement of carbohydrate into exercising cell (thus decreasing demands on the pancreas cells that make insulin) but also to increase insulin effectiveness (which also translates into a decreased demand on the pancreas). And this enhancement of the effectiveness of insulin lasts up to 16 hours after a bout of strenuous exercise.

So not only will an exercise program help you if you are trying to lose (and maintain) a new weight, for those of us of normal weight, it MAY decrease the odds of developing diabetes by decreasing insulin production demands on the pancreas cells (this is speculation on my part, but all the facts point in this direction).


Sitting for 6 to 8 hours a day increases the risk of early death and heart disease by 13% with that risk increasing to 20% for those sitting for more than eight hours a day.

Recent papers have suggested that even after focused daily exercise sessions (aerobic exercise at the gym, high intensity intervals), long periods of sitting will blunt the health benefits, but spacing physical activity throughout the day offsets this negative.

This study assessed the results of taking hourly exercise breaks (5 minutes) over an 8 hour period compared to sitting (mimicing a sedentary workday at a desk). The group taking exercise breaks had a much more healthier blood sugar/insulin profile as well as significant improvements in their level of fatigue and mood (notably vigor). To quote an author of the paper: "You can't just exercise for 30 minutes every morning and go sit the rest of your day. Your body needs perpetual regular movement. That's the key here. Our body needs regular 'activity snacks' throughout the day to operate well or optimally."

And this paper explains why. For several hours after exercise there is an increased insulin sensitivity which facilitates movement of glucose and amoino acids into the muscle cells at lower blood insulin levels and the lowering of an insulin spike is behind the health benefits. We now have the evidence that short burst of activity (just a few minutes every hour or so) can improve how the body processes sugar and amino acids.

It appears that maximizing the health benefits of a day's aerobic training (or HIIT) at the gym or of a long walk to log 10,000 steps requires additional physical activity spread throughout the day. Something every hour - a short walk around the office, a sprint up the stairs at home, or a set of squats next to your chair. This will not improve your VO2max or extend the length of your next endurance ride, but will add healthy days (and hopefully years) to your life. And focusing any additional physical activity around meals - a short walk before or after - provides a bonus by adding an insulin sensitizing benefit where it is most needed during the few hours after a meal when the bulk of the daily carbohydrates and amino acids are being shunted from the digestive tact into storage in the muscles.


The last few years have seen a dramatic increase in the number and type of tools for metabolomic investigations. This paper is a fascinating example of how detailed these investigations into exercise physiology have become.

First, a couple definitions:

The following are excerpts from a New York Times review of the work.

Scientists "decided complete a full census of almost every molecule that changes when we work out." Study participants were "asked complete a standard treadmill endurance test, running at an increasing intensity until exhaustion, usually after about nine or 10 minutes of exercise." Blood was drawn at time 0, immediately after this exertion, and again 15, 30 and 60 minutes later.

The scientists "...measured the levels of 17,662 different molecules. Of these, (the concentrations of) 9,815 - or more than half of those studied - changed after exercise. Some increased. Others declined. Some gushed immediately after the exercise, then fell away, while others lingered in heightened or lowered amounts for an hour after the workout. The types of molecules ....ranged widely, with some involved in fueling and metabolism, others in immune response, tissue repair or appetite."

This study highlights the complexity of human physiology. For most of us, it is enough to know that exercise helps keep our system younger. How exercise achieves that end is buried in these 9815 organic molecules. But each of these thousands of molecules, once categorized and studied in detail, will give the clues we need to improve the health of those not as compulsive about doing their intervals. And the hope that following blood levels of a subset of these molecules might give us the clues we need to maximize improvement with a truly individualized training program.

If you exercise regularly for health reasons, physiologists used a similar approach (original research) to compared the effects of resistance and aerobic exercise on that part of the metabolome that impacts cardiac health. Their impression - aerobic exercise provided more cardiovascular benefits than resistance training.


Aerobic athletes have lower rates of mortality from cardiovascular disease. To quote "Elite endurance (aerobic) athletes and mixed-sports (aerobic and anaerobic) athletes survive longer than the general population, as indicated by lower mortality and higher longevity with lower cardiovascular disease mortality the likely the primary reason for their better survival rates. On the other hand, there are inconsistent results among studies of power (anaerobic) athletes."

The "paradox", in endurance athletes, is a low cardiovascular mortality in the face of high rates of coronary artery disease (plaques) on imaging studies. And a recent study suggests a "J" shaped curve with some protection from coronary vascular disease at moderate levels of exercise, but increases in disease at higher volumes of training and competing. (additional editorial comments). Maximum protection from atherosclerosis was noted at 3 hours/week of moderate exercise, in line with current US health guidelines which suggest 150 to 300 minutes of moderate exercise (brisk walking) or 75 to 150 minutes of more vigorous activity (running), per week.

Calcified plaques tend to be stable while non calcium plaques often rupture leading to an acute blockage of the coronary artery and in turn a cardiac event. Perhaps endurance athletes have a more favorable ratio with more calcified plaques and fewer unstable plaques. But this study shows that is not the case. Not only do lifelong endurance athletes have more coronary plaques than fit and healthy individuals with a similarly low cardiovascular risk profile, they have a ratio of stable to unstable plaques that is similar to a group with healthy lifestyles.

So the search continues for an explanation for the paradox of more coronary disease but lower cardiovascular mortality. Possibilities such as (my ideas here) that these athletes have better collateral circulation and are thus better able to withstand an acute obstruction of one of the larger coronary arteries. Or perhaps some other factor that improves the stability of their uncalcified plaques.


Chakravarty EF, Hubert HB, Lingala VB, Fries JF.

Exercise has been shown to improve many health outcomes and well-being of people of all ages. Long-term studies in older adults are needed to confirm disability and survival benefits of exercise. METHODS: Annual self-administered questionnaires were sent to 538 members of a nationwide running club and 423 healthy controls from northern California who were 50 years and older beginning in 1984. Data included running and exercise frequency, body mass index, and disability assessed by the Health Assessment Questionnaire Disability Index (HAQ-DI; scored from 0 [no difficulty] to 3 [unable to perform]) through 2005. A total of 284 runners and 156 controls completed the 21-year follow-up. Causes of death through 2003 were ascertained using the National Death Index. Multivariate regression techniques compared groups on disability and mortality.

RESULTS: At baseline, runners were younger, leaner, and less likely to smoke compared with controls. The mean (SD) HAQ-DI score was higher for controls than for runners at all time points and increased with age in both groups, but to a lesser degree in runners (0.17 [0.34]) than in controls (0.36 [0.55]) (P < .001). Multivariate analyses showed that runners had a significantly lower risk of an HAQ-DI score of 0.5 (hazard ratio, 0.62; 95% confidence interval, 0.46-0.84). At 19 years, 15% of runners had died compared with 34% of controls. After adjustment for covariables, runners demonstrated a survival benefit (hazard ratio, 0.61; 95% confidence interval, 0.45-0.82). Disability and survival curves continued to diverge between groups after the 21-year follow-up as participants approached their ninth decade of life. CONCLUSION: Vigorous exercise (running) at middle and older ages is associated with reduced disability in later life and a notable survival advantage.


Fifty years before Darwin and his theory of natural selection, Lamarck theorized that an organism would pass on environmental adaptations to its offspring. If you cut the tails off three or four generations of mice, you'd soon see a few tail-less babies. Darwin, on the other hand, felt that our genes were hardwired and inherited unchanged from our parents. And then passed unchanged to our kids. Life experiences did not affect future generations. You could cut off as many mouse tails as you'd like but would never see tail-less mice in future litters.

This assumption of a hard wired inheritance ruled the science of genetics for over a hundred years. However the last few decades have seen a shift in this absolutist view. Why are two identical twins (exactly the same genetic makeup or genotype) often slightly different in appearance (phenotype)?

The study of differences in genetic expression, that is how identical genes are turned on, off, or are somewhere in between, is called epigenetics. A specific cell protein, miRNA, seems to be the switch that impacts how our hardwired genetic code is interpreted. And lifestyle has been shown to directly impact cell miRNA levels.

A recently published study on brain physiology shows the link between the increase in miRNA levels in the brains of regularly exercised mice and a corresponding increase in brain nerve cell connections. This was not unexpected as we knew from prior investigations that the level of our exercise directly correlates with brain health.

But surprisingly the researchers also found the same increase in miRNA levels in the sperm of the exercising group as well as improved brain development in their offspring. (It is fair to assume that the same miRNA changes occurred in the eggs of exercising female mice, but it was a lot easier for the experimenters to collect sperm from male mice than harvest eggs from the females).

These elevated miRNA changes in the babies soon returned to normal levels if the baby mice did not exercise as they grew. And the grand kids of the original study mice returned to a normal pattern of mouse brain development as would be expected with a similar, unaltered genetic makeup.

Even though this study focused on exercise, we know that other daily activities and exposures can impact miRNA levels, and that miRNA levels can in turn impact other aspects of genetic expression including, for example, cancer development.

It has been speculated that exposure to toxins in our environment (pesticides for example), medications and illicit drug use, and even diet can impact on our miRNA. Thus our development (and our kids in turn) is not just limited to the genes we inherit from our parents (and their parents).

This means that you can have direct, but limited, control to maximize the benefits of your genes and in turn your genetic contribution to your kids. But for that extra bit of benefit to be passed on to another generation, your kids would also have to adopt a similar "healthy" lifestyle.

And while you are helping give your kids a healthy boost to their genes, you will benefit from this healthy lifestyle. The exercising mice all benefited from a more connected network of nerve cells in their brains which it can be speculated will translate into a decreased tendency to develop Alzheimer's. And we also have that suspected link between miRNA levels and cancer development. So when you are vacillating on that decision to buy the slightly more expensive pesticide free produce at the local grocery store, or get out for that all too easy to skip afternoon walk, remember that it is not only for you.

The original NYT article that got me thinking.


This interesting study on exercise and immunity found that "..125 long-distance cyclists, some now in their 80s, .....had the immune systems of 20-year-olds."

As nicely summarized by Dr. Mirkin "T-cells recognize foreign proteins on the surface of invading germs and cancers to tell your immunity to attack and kill these cells. They then stimulate your immune system to make antibodies to attach to and kill invading germs and cancer cells, and produce chemicals called cytokines that activate other T-cells to remove germs and cancer cells from your body. Other regulatory T-cells dampen down your immunity so that your immunity does not attack and destroy your own healthy cells."

The study suggests that this weakening of the aging immune system is from a significant reduction in thymic activity and the production of T cells. This senescence is blunted in regular cyclists, and to quote: "....many features of immune senescence may be driven by reduced physical activity with age."

But the maxim "if a little is good, a lot must be better" apparently doesn't apply to the disease protective benefits of exercise. A new study indicates that intense exercise (we are talking marathon, a century ride levels) increases the odds of URTIs (upper respiratory tract infections). The average person on a moderate exercise program won't trigger these negative immune system changes but those who exercise to the extreme should make an extra effort to get proper rest and recovery in order to maintain a robust immune system.


Exercise is a positive addition to chemotherapy. As documented in this study exercise not only prevents fatigue and decreases in VO2peak, and muscle strength but hastens the return of function after chemotherapy. If exercise is limited or impossible during chemo, beginning a program afterward will hasten a return to pre treatment levels of fitness. In this study, all participants were able to restore their fitness to baseline 1 year after completing the exercise regimen.

A separate study suggested that patients with the highest level of cardiovascular fitness had a 25% decrease in post treatment mortality. Thus exercise not only limits the immediate impact of chemotherapy on quality of life but has an additive effect on the ultimate survival.


Some of us exercise to improve our aerobic capacity for our weekend group ride with friends or competitive events. But many more have taken on a regular exercise program to improve their cardiovascular health (lower the risk of a heart attack) or after being told they had an elevated fasting blood sugar and were borderline diabetic.

For improving athletic performance, timing of the days training is determined by what works to maximize a regular training schedule. But for metabolic health, especially for those with altered glucose metabolism, this paper indicates that the timing of exercise will make a difference in health benefits gained.

To quote from a NYT article on the study: "After 12 weeks, the men who had pedaled in the afternoon displayed significantly better average insulin sensitivity than the morning exercisers, resulting in a greater ability to control blood sugar. They also had dropped somewhat more fat from around their middles than the morning riders, even though everyone’s exercise routines had been identical."

So if you have the flexibility, a vigorous walk or hour on the bike in the afternoon provides more health benefits than exercise in the early morning. I personally prefer a walk immediately before or after my noon or evening meal as timing of this exercise (which stimulates glucose movement into the muscles) blunts the post meal blood sugar rise. And more and more work is pointing to the height of that blood sugar spike as a culprit in the development of cardiovascular disease.

EXERCISE AND HEALTH BENEFITS (Is more better? How much is enough? Too much?)

For general health - BP control and lipid management - is more always better? And even more important, can you do yourself harm by exercising too much? As we review the data, the two important variables are time and intensity. Let's use the definitions in this paper (and additional discussion). Moderate physical activity (MPA) is walking, weightlifting, calisthenics. Vigorous physical activity (VPA) includes jogging, running, swimming, bicycling, playing squash/racquetball/tennis, and climbing stairs.

Prior to this paper, 75-150 min/wk of MPA (30 minutes - 4 times a week) was felt to provid maximum health benefits. But when exercisers were separated by level of activity, MPA and VPA, there was an increasing benefit from moderate activity up to 300 minutes per week (1 hour - 4 times a week). Although a graph in the paper suggest benefit from longer times, this was felt to be statistically significant.

For VPA, the benefit break occurs sooner - at 150 minutes per week. (Although prior studies have suggested an actual increase in cardiovascular risk from longer vigorous activity, a slight upward trend in this study was not felt to be statistically significant.)

What are the take aways?

  1. If you are walking for your exercise, more minutes = incrementally better health outcomes up to 300 minutes a week. Plus the suggestion of additional, but increasingly smaller, benefit from any added exercise time, and definitely no harm from additional walking or recreational cycling beyond this point.

  2. If you have limited time, running or cycling (especially if it is high intensity) gets you the same health benefit in half the time with the maximum at 150 minutes per week.

  3. The jury remains out on the question of harm from greater than 150 min of intense activity per week.

  4. Any exercise is better than no exercise. To quote from a NYT review: "All exercise is good, but there are nuances. Frequent, almost-daily moderate exercise may be preferable for improving blood pressure and ongoing blood-sugar control, compared to infrequent intervals, while a little HIT is likely to get you in shape as effectively as hours and hours of easier cycling or similar exertion."


Does it matter how you reach your 150 - 300 minutes. This study suggested adults performing 150 minutes of physical activity per week gained equal health benefits from sessions spread throughout the week as they did from a one day extended session of activity (the weekend warrior).

However this flies in the face of many other studies on the health benefits of exercise. In diabetes (a common medical condition wiht a significant impact on population health and mortality figures) multiple studies confirm more exercise means less health problems. This is one example.

However the recommendation from the diabetes experts is to spread the activity across the day. "Prolonged sitting interrupted by brief (< 5 min) bouts of standing or light-intensity ambulation every 20-30 min improves glycemic control in sedentary overweight/obese populations and in women with impaired glucose regulation. In adults with type 2 diabetes, interrupting prolonged sitting with 15 min of postmeal walking and with 3 min of light walking and simple body-weight resistance activities every 30 min improves glycemic control."

A major health benefit of exercise is the result of moderating blood sugar spikes after eating. Thus it seems logical to focus physical activity in the post meal period. Get up from the table and take a short 15 minute walk, even if it is just up and down the stairs or around the house.

My conclusion? If one of the reasons for your ride is for its health benefits, do some riding, even a short 30 minute spin, every day. And you will get bonus points for additional short walking breaks during the day.


Google Metformin and you will find numerous blogs and articles suggesting it as a longevity promoting, anti aging wonder drug. For example "A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Health span and Extends Lifespan"

This article summarizes the optimism. To quote "Emerging evidence suggests the drug may be effective for a much broader range of conditions beyond managing high blood glucose, including various cancers, obesity, liver disease, cardiovascular, neurodegenerative, and renal diseases."

Metformin is thought to work via "activation of AMP [adenosine monophosphate]-activated protein kinase, a central pathway in metabolic regulation..." Since it is involved in energy metabolism, is it possible it might also improve aerobic performance? Unfortunately no. Here are the results of a controlled trial - "VO2 peak (-2.7%), peak heart rate (-2.0%), peak ventilation (-6.2%), peak RER (-3.0%), and exercise duration (-4.1%) all reduced slightly, but significantly, with metformin."

Metformin does increases insulin sensitivity - which is why it is a first line diabetic medication - but interestingly when studied in active adults, blunts the improved insulin sensitivity that comes with regular exercise.

Where does that leave us?

  1. If you have diabetes (or prediabetes - trials in process), metformin is a great drug.
  2. If you are not a regular exerciser, you are in a group that may experience a benefit from metformin - the proof is not yet in.
  3. If you are a healthy older athlete, considering metformin for its potential longevity effects, you need to consider its potential to slightly decrease in your athletic performance. And as exercise has already proven health promoting benefits, likely equivalent to if not superior to metformin, it doesn’t seem worth the risk to start a new unproven medication.

    All questions and suggestions are appreciated and will be answered.

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