✶Explainer10:30
Rapamycin May Slightly Trade Muscle Adaptation for Lower Inflammation
Baar says longevity-level rapamycin doses should have only a minimal effect on skeletal-muscle adaptation for most people, while still exerting some negative effect. He explains that both muscle and immune cells use mTOR activity to respond to stress, so suppressing the pathway can affect hypertrophy and immune function as well as inflammation.
- mTOR complex one helps skeletal muscle respond to resistance exercise
- Baar expects ordinary longevity dosing to have a small negative effect on muscle adaptation
- The trade-off may matter more to elite competitors pursuing maximal hypertrophy
- Immune cells also need mTOR activity to respond to challenges
“The short answer is that at the doses that they're taking for longevity, you have a minimal effect on the adaptation of skeletal muscle, but…”
“Our immune cells, they are doing similar things. They need mTOR activity in order to respond to an immune challenge.”
#rapamycin#mtor#hypertrophy#inflammation
✶Explainer04:30
Strength Depends on Force Transfer, Not Only Muscle Size
Baar recounts arriving at the English Institute of Sport believing strength should rise with muscle cross-sectional area, only to see cyclists becoming stronger while staying the same size or getting smaller. He explains that muscular force must travel through tendons, connective tissue, and other force-transfer proteins before it can move bone.
- Muscle size is only one contributor to strength
- Force produced by muscle must be transmitted to bone
- Tendons and connective tissue are part of the performance system
- Athletes can become stronger by improving force transfer without adding mass
“I've got five years of data that shows me I'm getting these athletes stronger without making them any bigger. And in many cases making them…”
“And that force has to be transmitted from our muscle where we're producing it to our bone where the movement is going to occur.”
#strength#force-transfer#tendons#muscle
✶Explainer51:00
How Strong Permanent Sutures Can Shield Native Achilles Tissue
Baar argues that reinforced non-resorbable sutures can carry so much load that the repaired native tendon remains stress-shielded and loses capacity. He describes a rat study from his lab in which resorbable and non-resorbable repairs had similar strength and Achilles length at four weeks, while the resorbable repair showed better collagen-synthesis markers.
- Very strong sutures can take load that would otherwise reach native tissue
- Stress-shielded native tissue may become smaller over time
- Baar's rat study found no four-week strength difference between the two suture types
- He says resorbable repair works best with a team skilled in early loading
- The episode presents this as research, not personal surgical advice
“So if you load that, where do you think the load is going to go? It's going to go to the sutures.”
“We saw that the resorbable actually had better like collagen synthesis markers than the non-resorbable, just kind of like what we would anticipate.”
#achilles#sutures#surgery#stress-shielding
✶Explainer1:16:00
The JAK Inhibitor Signal That Made Engineered Tendons Stronger
Baar's team compared gene activity in developing rat tendons and found JAK-STAT inhibition associated with growth in the patellar tendon. He says three inhibitors targeting different JAK combinations all made engineered tendons bigger and stronger, but a development study also produced animals that were 40 percent smaller, underscoring that the work is early and has major trade-offs.
- The team used transcriptomics to compare growing Achilles and patellar tendons
- JAK-STAT inhibition was the major signal in the tendon increasing cross-sectional area
- JAK1, JAK1/2, and JAK3 inhibitor experiments all appeared beneficial in engineered tendons
- The exact responsible target remained unresolved
- Developmental exposure impaired longitudinal growth in the animals
“So, what we found is that when we used those drugs, the tendons that we engineered got bigger and stronger.”
“And one of the first things that we found is that the animals were 40% smaller.”
#jak-stat#tendon-growth#drug-research#transcriptomics
✶Explainer1:19:00
A Finnish Registry Linked Sartan Drugs to Higher Tendon-Rupture Rates
Baar describes a Finnish registry study that examined medications used by people who ruptured an Achilles tendon. He says fluoroquinolone antibiotics were associated with roughly a 3.5-fold increase, while angiotensin AT1-receptor drugs—the sartan class—were associated with a 7.6-fold increase, and he stresses the need to balance cardiovascular treatment with musculoskeletal function rather than giving personal medication instructions.
- The reported evidence comes from a Finnish registry analysis
- Fluoroquinolone antibiotics were associated with about a 3.5-fold higher rupture rate
- Sartan-class drugs were associated with a 7.6-fold higher rupture rate
- Baar says the association is not widely recognized despite common use
- Reduced activity after major ligament injury can itself raise cardiometabolic risk
“So you you find the fluoroquinolone antibiotics, yep, they're there, but they increase rupture rate about three and a half fold.”
“and they increase the rate of tendon rupture 7.6 fold.”
#sartans#fluoroquinolones#tendon-rupture#medications
✶Explainer1:23:00
How Estrogen and Testosterone Alter Connective-Tissue Stiffness
Baar explains that estrogen reduced engineered-ligament stiffness without reducing collagen content by inhibiting the enzyme that cross-links collagen. He contrasts this with testosterone, which he says increases cross-linking while decreasing collagen, potentially producing a stiff but brittle tendon when stronger muscles place greater force on it.
- Women are four to eight times more likely to rupture an ACL, according to Baar
- Estrogen reduced stiffness in the engineered ligaments without lowering collagen content
- Collagen cross-linking changes stiffness independently of total collagen amount
- Baar links testosterone-related products with stiffer, lower-collagen tendons
- Tendon stiffness affects how quickly muscular force can be transmitted
“And what we found is that the stiffness of the ligament went down.”
“It actually activates lysyl oxidase and it decreases collagen. So what you get is you get a stiff tendon that has less collagen and that's…”
#estrogen#testosterone#acl#connective-tissue
✶Explainer1:33:00
The Ketogenic Diet Trade-Off: Mitochondria and Longevity vs. Speed and Bone
Baar compares ketogenic eating with low-dose rapamycin because both reduce mTOR activity, and reports that mice in his controlled study lived 13 percent longer on the ketogenic diet. He also says the diet can promote mitochondrial quality through mitophagy, but warns that athletes lose high-speed carbohydrate-supported capacity and that bone mass is a serious concern, especially with osteoporosis risk.
- Baar's mouse study combined ketogenic eating with one meal daily and modest calorie restriction
- The ketogenic group lived 13 percent longer than controls
- Low carbohydrate availability pushes greater reliance on mitochondria and promotes mitophagy
- Baar says ketogenic diets are unsuitable for athletes who need to sprint
- He identifies bone loss as the diet's largest downside
“What we found is that the ones on a ketogenic diet live 13% longer than the ones on the control diet.”
“The important thing is, and we wrote a paper on this, is that if I'm an athlete, ketogenic diet is not for me.”
#ketogenic-diet#mitochondria#longevity#bone-health