Dr. Peter Attia in conversation with Dr. Andrew Huberman: Just for reference: Smoking is a 40% increase in all-cause mortality (ACM). That means, at any point in time, a smoker is 40% more likely to die than a non-smoker. High blood pressure is a 20-25% increase in ACM. Type 2 diabetes is a 25% increase in ACM. Low muscle mass people have a 200% increase in ACM compared to people with high muscle mass. People who are in the bottom 25% for their age and sex in terms of VO2 max and you compare them to people that are people at the 50th to 75th percentile, that is a 200% risk of ACM. The benefits of exercise are such that arguments over supplements or diets are silly until exercise is in order.
Stillness is bad. Roughly 3.2 million people die each year because of physical inactivity. Regular exercise, especially among older adults, is critical to good health. The results of 13 studies describing eight different cohorts suggest that regular physical activity is associated with an increase of life expectancy by 0.4 to 6.9 years.
Insulin release is suppressed while exercise is happening. Reduced insulin activity contributes to healthy aging and longevity.
Muscular strength is inversely and independently associated with death from all causes and cancer in men, even after adjusting for cardiorespiratory fitness and other potential confounders. This video clarifies the value of strength.
Regular physical activity is one of the most important things you can do for your health. Being physically active can improve your brain health, help manage weight, reduce the risk of disease, strengthen bones and muscles, and improve your ability to do everyday activities. Regular exercise (resistance and aerobics) has a huge effect on muscle functioning and, ultimately, healthspan. But don’t overdo resistance training.
Dr. Peter Attia: Four types of exercise should be done: stability, strength, aerobic efficiency, and anaerobic peak. Exercise is a slam-dunk for every chronic malady, including cancer. Minimum: three hours per week.
An accelerometer (no cheating!) study of 4840 adults aged 40 to 85 years or older found that approximately 110 000 deaths per year could be prevented if US adults aged 40 to 85 years or older increased their moderate-to-vigorous physical activity intensity by a small amount (ie, 10 minutes per day).
In a study of 122 007 consecutive patients undergoing exercise treadmill testing, cardiorespiratory fitness was inversely associated with all-cause mortality without an observed upper limit of benefit. Extreme cardiorespiratory fitness (≥2 SDs above the mean for age and sex) was associated with the lowest risk-adjusted all-cause mortality compared with all other performance groups.
A sedentary lifestyle (in addition to smoking, high body mass index, and low socioeconomic status) has an effect on leukocyte telomere length and may accelerate the aging process. Conversely, long-term exercise training activates telomerase and reduces telomere shortening in human leukocytes. The age-dependent telomere loss was lower in the master athletes who had performed endurance exercising for several decades. Also, telomerase may be protective of mitochondrial function, and the paper here lists a few other interesting line items as well: angiogenesis, metabolism, regulation of gene expression, and so forth.
Walking/cycling, sleeping, and moderate to vigorous activity were associated with a slower rate of aging according to PhenoAgeAccel. In contrast to this, sedentary behavior was associated with a faster rate of aging by the same metric.
For longevity, moderate exercise with occasional bouts of vigorous exercise, is recommended. For the same volume of moderate to vigorous physical activity, a higher proportion of vigorous physical activity to total physical activity was associated with lower all-cause mortality

Drive less, walk and cycle instead.
Exericise for slower tendon ageing. Exercise slows age-related idiopathic pulmonary fibrosis . Exercise can save a ton of money in healthcare costs. In a very real sense, our muscles make our own precision medicine. It’s a targeted cascade of chemicals that help prevent disease, repair injury, and help us live longer, healthier lives.
Tommy Wood MD, PhD in conversation with Dr Rangan Chatterjee, discusses the contribution of muscle and exercise to health.
Grip strength (muscle mass) is inversely associated with DNA methylation age acceleration.
This study recruited 125 amateur cyclists aged 55 to 79, 84 of which were male and 41 were female. The men had to be able to cycle 100 km in under 6.5 hours, while the women had to be able to cycle 60 km in 5.5 hours. Smokers, heavy drinkers and those with high blood pressure or other health conditions were excluded from the study. The study showed that loss of muscle mass and strength did not occur in those who exercised regularly. The cyclists also did not increase their body fat or cholesterol levels with age and the men’s testosterone levels also remained high, suggesting that they may have avoided most of the male menopause. More surprisingly, the study also revealed that the benefits of exercise extend beyond muscle as the cyclists also had an immune system that did not seem to have aged either.
Regular exercise has multi-system anti-aging effects:
High intensity interval training (HIIT) is known to elicit higher enjoyment than moderate-intensity continuous training (MICT), as reported by original research and meta-analysis, making the interval training model a practical and enjoyable exercise mode for the general population. Vigorous (acute) and sustained exercise is best (break a sweat!): don’t overestimate effort. High-intensity interval training promotes neuroplasticity. Vigorous exercise increases BNDF in parts of the brain not reached by mild exercise.
Too much HIIT could disrupt athletic performance and metabolism, and maybe destabilize your blood sugar. About 90 minutes a week is a safe amount of HIIT for healthy people.
Doctors call physical exercise a “polypill,” because it can prevent and treat many of the chronic diseases that are associated with aging. “Exercise is the most powerful drug we have,” says Dr. Kevin Murach, assistant professor at the Exercise Science Research Center, University of Arkansas, Fayetteville, AR.
Exercise may turn back the clock in muscle fibers by promoting the “epigenetic reprogramming” of chromosomes in the cells’ nuclei. Exercise reprograms muscle fibers to a more youthful state through increased expression of the genes that make Yamanaka factors, in particular Myc.
Different forms of exercise induce neuroplasticity changes in different brain regions, and thus exert diverse effects on various forms of learning and memory.
Exercise can save a ton of money in healthcare costs. In a very real sense, our muscles make our own precision medicine. It’s a targeted cascade of chemicals that help prevent disease, repair injury, and help us live longer, healthier lives. Exercise beats drug treatment. Exercise beats vitamins for preventing falls. and helps preserve independence. Resistance exercise works via preventing falls and broken bones. Even once per week helps. Regular exercise can really improve your proprioception and coordination, meaning if you are a clumsy person, you can fix that.
From a video by Dr. Brad Stanfield: For building muscle mass and for maintaining muscle mass through a positive muscle protein balance, an overall daily protein intake in the range of 1.4–2.0 g protein/kg body weight/day (g/kg/d) is sufficient for most exercising individuals, a value that falls in line within the Acceptable Macronutrient Distribution Range published by the Institute of Medicine for protein.
Exercise improves mitochondria
Exercise throughout life will, via AMPK, preserve the functionality of mitochondria. Functioning mitochondria are essential to avoid chronic diseases. The therapeutic effects of endurance exercise are accompanied by a number of physiological adaptations, however, one of the most beneficial effects appears to be stimulation of mitochondrial biogenesis in a wide variety of tissues including the brain. Mitochondria contribute to stem cell maintenance.
Mitochondria contribute to specific aspects of the aging process including cellular senescence, chronic inflammation and the age-dependent decline in stem cell activity. Mitochondria influence or regulate a number of key aspects of aging, and suggest that strategies directed at improving mitochondrial quality and function might have far-reaching beneficial effects.
This study of 5,446 women in the United States who were 63 and older found that higher levels of light physical activity and moderate-to-vigorous physical activity were associated with lower risk of death. Higher sedentary time was associated with higher risk of mortality. These associations were consistent among women who had different levels of genetic predisposition for longevity.
High intensity exercise induces more short-term inflammatory cell stress, but removes more of the pre-existing markers of cellular senescence as a result of a greater immune reaction to that stress.
From Harvard Health: Researchers found that people who followed the minimum guidelines for physical activity—150–300 minutes per week of moderate-intensity activity, or 75–150 minutes per week of vigorous-intensity activity—reduced their risk of early death by as much as 21%.
Women interested in reducing belly fat and blood pressure, while at the same time increasing leg muscle power should consider exercising in the morning. However, women interested in gaining upper body muscle strength, power, and endurance, as well as improving overall mood state and food intake, evening exercise is the preferred choice. Conversely, evening exercise is ideal for men interested in improving heart and metabolic health, as well as emotional wellbeing.

Exercise above the recommended amount can provide greater health benefit. People in hunter-gatherer societies generally don’t run every day, yet they enjoy a long healthspan. Being obese is no excuse: the obese benefit from exercise like anyone else.
The benefits of walking are pointed out by Dr. Michael Greger (with lots of references).
This study of U.S. adults aged 40 and over with approximately 4,800 participants who wore accelerometers for up to seven days between 2003 and 2006 found that, compared with taking 4,000 steps per day, taking 8,000 steps per day was associated with a 51% lower risk for all-cause mortality. Taking 12,000 steps per day was associated with a 65% lower risk compared with taking 4,000 steps.
It is possible to overdo exercise: Chronic excessive endurance exercise might adversely impact CV health. Ultra-endurance races can inflict acute myocardial damage, as evidenced by elevations in troponin and brain natriuretic peptide. Moreover, sudden cardiac arrest occurs more often in marathons and triathlons than in shorter races. Veteran endurance athletes often show abnormal cardiac remodeling with increased risk for myocardial fibrosis and coronary calcification. Chronic excessive exercise has been consistently associated with increased risks of atrial fibrillation (AF), and along with some attenuation of longevity benefits.
Never too late to exercise
These two doctors (Talking with Docs) pointed out this excellent study of 100,000 people in their 70’s that, besides confirming that aerobic exercise is wonderful, also confirmed that resistance training will seriously extend one’s lifespan and avoid chronic diseases. No excuses, regardless of health or age.
Sedentariness appears a far more dangerous condition than physical activity in the very old. A 2022 study found that healthy older men who lifted weights strengthened the connections between their nerves and muscles, helping them maintain physical function. The subjects’ average age was 72, but they were just kids compared to participants in a landmark 1990 trial that looked at frail, institutionalized people as old as 96.
Dr. Andrew Huberman, in this video, states that muscle strength starts declining in one’s 30s. The rate of decline accelerates at age 60. So, exercise is more important as one gets older. Resistance training causes muscle to be less insulin resistant.
Resistance training modulates reticulum endoplasmic (blood vessel) stress, independent of oxidative and inflammatory responses, in elderly people. Regular physical activity is suggested to be an effective intervention in improving age-related diseases such as osteoporosis, sarcopenia or muscle loss and dynapenia or loss of muscle strength, cardiovascular diseases, and type 2 diabetes.
For adults 60 and older, the risk of premature death leveled off at about 6,000-8,000 steps per day, meaning that more steps than that provided no additional benefit for longevity. Adults younger than 60 saw the risk of premature death stabilize at about 8,000-10,000 steps per day. JAMA also suggests 8,000 steps per day.
This10-year cohort study was conducted with 152 self-caring and mobile, mean age 80 years found that, after adjusting for sex, age, education, chronic diseases, smoking, and body mass index, elderly people walking at open air for four times weekly had 40% decreased risk of mortality that individuals who walked less than four times weekly.
Walking fast conferred the greatest benefit in this study of 474,919 people with an average of 64.8 years for men and 72.4 years for women.
Creatine supplementation is effective in lower limb strength performance for exercise with a duration of less than 3 min, independent of population characteristic, training protocols, and supplementary doses and duration.