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In this episode of Longevity By Design, co-hosts Ashley Reaver, MS, RD, CSSD, and Dr. Gil Blander welcome renowned professor Dr. Keith Baar. As the head of the Functional Molecular Biology Lab at UC Davis, Dr. Baar has made groundbreaking discoveries about how exercise and nutrition influence the adaptation of muscles, tendons, and ligaments. During this episode, he shares his expertise on the critical role of exercise and nutrition for musculoskeletal health, longevity, and improving quality of life.
Dr. Baar discusses the profound impact that both strength and endurance exercise have on healthspan and longevity, emphasizing the unique benefits of strength training. He delves into the molecular biology of muscles, explaining his discovery that resistance exercise activates the mTOR pathway, which is crucial for muscle protein synthesis and muscle growth. He also shares his knowledge on the effects of the drug rapamycin, an inhibitor of mTOR, on muscle versus longevity, highlighting the nuances and complex balance needed for optimal health.
Dr. Baar also shares his expertise and addresses common misconceptions regarding tendons and ligaments. The conversation also covers the significance of nutritional timing, the benefits of integrating protein intake with exercise for muscle, and collagen and vitamin C for tendons and ligaments.
Listeners to this episode will be equipped with an understanding of the responses to different types of exercise and practical exercise and nutrition advice for optimizing muscle, tendon, and ligament health througout life.
Episode highlights
Dr Keith Baar received his Bachelor’s in Kinesiology from the University of Michigan, a master’s degree in muscle physiology from the University of California, Berkeley, and his Ph.D. from the University of Illinois, where he discovered the molecular signal that causes muscle to grow bigger in response to resistance exercise. He did his postdoctoral research at Washington University in St. Louis, where he identified the molecular signal that leads to increased capillaries and mitochondria in muscle in response to endurance exercise. He then returned to Michigan with Dr. Robert Dennis, where he learned to engineer skeletal muscle and extended the work to include the heart, the first functional smooth muscle organoids, and the first engineered tendons. Keith opened his first laboratory at the University of Dundee in Scotland where his group engineered the first ligaments from bone-to-bone.
Keith is currently the head of the Functional Molecular Biology Laboratory (FMBLab) at the University of California Davis. His research is focused on determining the effect of exercise, nutrition, age, and disease on musculoskeletal tissue function. Work from his lab spans from the molecular mechanisms that lead to adaptation to human studies that translate these basic discoveries to interventions that improve longevity and quality of life.
Dr. Baar emphasized that while diseases like cancer and heart disease get a lot of attention, inactivity is actually responsible for nearly 20% of deaths in the United States.
"The fact is that one in three visits to a doctor is because you've had a tendon, muscle or connective tissue injury. And so there's this huge component of our society that is, you know, we'll say go out and exercise. Everybody knows that all you have to do is exercise is going to improve your longevity...But so many people are injured and can't do it, that it becomes really, really difficult to actually provide that evidence-based advice," states Dr. Baar.
He also noted that musculoskeletal injuries to areas like the neck and back cost the U.S. economy more than heart disease and diabetes combined. This highlights the massive burden that inactivity and musculoskeletal issues place on health and economic productivity.
Crucially, our muscle strength relative to our size is the greatest predictor of longevity. Being in the strongest third of the population can increase the chances of living by a staggering 100 to 250%. "There was a really nice study on Hawaiians, a 44-year longitudinal study. If you're in the strongest side of the population in your mid-forties to -fifties, you are two and a half times more likely to make it to 100 years of age." He contrasted this to high endurance capacity only providing about a 10% greater likelihood of reaching 100 years of age in that study population.
The reasoning is that maintaining enough strength to perform activities of daily living, move around, and avoid falls or injuries allows people to then engage in all the other behaviors that extend lifespan."Your strength is actually going to be one of your primary determinants for how long you live," explains Dr. Baar.
While endurance exercise is still beneficial, resistance training appears to have a bigger longevity impact according to Dr. Baar's analysis. He noted endurance exercise is more focused on boosting mitochondria, capillaries and metabolism in muscles.
In contrast, the downstream effects of resistance training including activating pathways like mTOR in muscles while suppressing it in other tissues could provide a more optimal systemic response for longevity. Combining the two exercise modes may allow people to "have their cake and eat it too" in terms of balanced mTOR activity.
However, Dr. Baar emphasized that higher intensity, out-of-breath resistance training a few times per week seems to provide superior longevity benefits compared to longer endurance sessions at an easier pace. The strength gains from lifting heavier ultimately seem to be more protective for maintaining functional capacity into older age.
During his PhD research, Dr. Baar made the groundbreaking discovery that the mTOR complex 1 (mTORC1) pathway is activated in skeletal muscle in response to resistance exercise. Crucially, the level of mTORC1 activation was proportional to the amount of load or weight lifted. This provided the molecular mechanism explaining how lifting heavier weights drives greater muscle growth and hypertrophy.
"What I discovered, what we discovered during my PhD is that when you lift a heavy weight in the skeletal muscle that you are working...you're going to activate mTOR complex one, and that's directly proportional to the increase in muscle mass that you're going to get," explains Dr. Baar.
While resistance exercise activates mTORC1 in working muscles to promote growth, Dr. Baar found the effects of exercise on mTOR are tissue-specific. For example, endurance exercise tends to suppress mTORC1 in metabolic tissues like the liver and fat. However, it leaves mTORC1 activated in the brain.
Resistance training has a similar "yin-yang" effect, with mTORC1 activated in exercised muscles but suppressed in liver, fat, and other tissues."If I do enough weight lifting, or if I do enough exercise that I've changed the metabolism within my body, I will simultaneously turn off mTOR in my liver. And I'll turn off mTOR in my adipose tissue, and then there's going to be signals that also reach the brain that turn on mTOR in the brain," explains Dr. Baar.
One of the key ways to improving longevity seems to be striking the right balance of mTOR activation and inhibition in different tissue beds. While complete mTOR inhibition via drugs like rapamycin can extend lifespan, it comes at the cost of inhibiting muscle growth.
However, Baar suggests resistance exercise may act "a little bit like a non-pharmaceutical rapamycin"—achieving a "perfect storm" by activating mTOR in muscles to drive growth and strength, while suppressing mTOR in other tissues.
A balanced approach of combining resistance and endurance training may optimize mTOR signaling for muscle growth and metabolic health in a way that promotes healthspan and longevity. Simply inhibiting mTOR consistently appears sub-optimal compared to modulating it through exercise.
While tendons and ligaments may seem similar, Dr. Baar explained their distinct roles and mechanical properties. Because tendons link compliant muscle to rigid bone, one end needs to be soft/stretchy while the other is stiff to prevent muscle tears. In contrast, ligaments connecting bones need to be uniformly stiff to stabilize the joint.
Dr. Baar's lab made the novel finding that cyclical estrogen changes in premenopausal women appear to modulate the stiffness of tendons and ligaments:
"What we discovered is that when we treated them (engineered ligaments) with estrogen, the lysyl oxidase enzyme that crosslinks and stiffens collagen actually got inhibited by 80%...that means the collagen within that structure is going to be more stretchy."
This helps explain why premenopausal women are more prone to ACL tears when estrogen surges make ligaments more compliant, yet are protected against muscle strains due to less stiff tendons.
The effects reverse after menopause, with tendons and ligaments becoming stiffer like men's. Certain breast cancer treatments that block estrogen also increase joint/tendon stiffness and related pain.
Understanding these gender differences allows tailoring of conditioning programs. Women may need extra tendon/ligament training to prevent ACL tears, while stiff tendons make men more susceptible to muscle strains without proper preparation.
Dr. Baar's lab has revealed some surprising findings about loading tendons and ligaments. Conventional wisdom is that tendons and ligaments respond best to heavy loading, similar to building muscle. However, Dr. Baar's research has overturned this notion, finding that relatively low loads provide the strongest anabolic signals for these connective tissues.
"What we figured out and learned very quickly was that our tendon cells and our ligament cells...our connective tissues...it's actually best to do very short five, six minutes of activity with about six to eight hours of rest," he explains.
This low-load "isometric" protocol involves holding a static position under tension for 5-6 minutes before resting. Baar found this stimulates tendons or ligaments maximally without overloading them. For example, the lab worked with rock climbers using an app to track finger tendon loading. Those doing brief 6-10 minute isometric holds saw similar finger strength gains as those lifting maximal weights.
There's a common misconception that severed tendons or ligaments require surgery to reconnect the "ropes." However, Baar's research shows these tissues can often repair themselves without invasive procedures:
"There's this idea that we have to go in and surgically repair any type of tendon or ligament injury because...if the ropes aren't connected, we just need to tie them back together. That's really not true. They actually turn over faster than our skeletal muscle...as long as there is a connection there, you should be able to repair that structure."
He cited cases of ACL tears successfully healing by simply bracing the knee to let the torn ends reconnect and repair themselves over time.
The isometric loading protocols can also facilitate this natural repair process for conditions like tennis elbow or golfer's elbow by stimulating the tendons involved without overloading them.
Overall, Baar's work highlights how low-load, intermittent tension provides the ideal anabolic stimulus for tendon/ligament adaptation and healing, without the need for surgery in many cases.
Proper protein intake, especially around the time of exercise, is crucial for supplying amino acids to build and repair muscle and connective tissues.
"If I exercise, even just small amounts of exercise, what I've done is I've put an address on where that protein or nutrient is going to go...if I take in any protein or food, now that increased blood flow is going to go to that working muscle for a longer period," explains Dr. Baar.
For younger, active individuals, the "anabolic window" for consuming protein may be more flexible, up to 24 hours after exercise. However, as we age and become more insulin resistant, timing protein intake closer to exercise becomes more important
"If you are an older person and you're trying to compete against getting old, what you want to do is work a lot of your muscle mass. And then if you deliver some amino acids or protein near that exercise, you're then going to deliver more of that substance to your muscles," states Dr. Baar.
Vitamin C plays a vital role in the production of collagen - the primary protein making up tendons, ligaments, and other connective tissues.
"Vitamin C is absolutely essential to the processing and the movement of that collagen protein out of the cell. So if we don't have vitamin C, we don't actually produce collagen and add it into the matrix," explains Dr. Baar.
This is why the disease scurvy, caused by complete vitamin C deficiency, leads to symptoms like reopening of scars, tooth loss, and hair loss due to lack of collagen production.
Ensuring adequate vitamin C intake, whether from foods or supplements, is critical for maintaining healthy collagen turnover and repair of connective tissues.
While the research is still early, Dr. Baar sees potential for collagen supplements to aid connective tissue repair, especially when demand is high like after an injury:
"If you have something like osteoarthritis or some sort of injury where there's been an increase in collagen production or a problem with collagen turnover, (collagen supplements) can be helpful."
However, for most healthy active individuals, a balanced diet containing collagen from foods like meat may be sufficient. More research is still needed to determine if supplementation provides consistent benefits.
Baar's own research is exploring if supplementing specific nutrients like collagen and vitamin C around the time of injury or surgery can enhance healing and collagen production in tendons and ligaments. But for general purposes, he doesn't currently recommend collagen supplements across the board.
The bigger priorities are ensuring adequate protein from foods, maintaining vitamin C levels, and implementing appropriate loading strategies to maintain tendon and ligament health long-term, says Dr. Baar.
Exercise at an intensity that leaves you out of breath a few times per week, and perform isometric holds to lightly load your painful joints and connective tissues, says Dr. Baar. This prudent mix of strenuous and controlled loading can optimize musculoskeletal function for an enriching life well into old age.
"We want to be able to do all the things that we love doing for as long as possible," says Dr. Baar.
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