November Research Wrap-Up
A summary of studies I covered in Physiology Friday this month... plus some practical takeaways.
Greetings,
In case you missed it, here’s a quick summary of all of the studies I covered in November Physiology Friday newsletters, including:
a “postbiotic” supplement that might help athletes squeeze out a little more performance.
a deep dive into why VO₂ max actually falls with age.
a clever lab study showing how even one low-activity day can change the way your body responds to exercise.
Enjoy, and remember, now through the end of the year, you can take 60% off a subscription to Physiologically Speaking.
Is Urolithin A the Next Big Performance Supplement?
This randomized trial looked at 42 highly trained male distance runners during a 3-week altitude camp. Half took 1,000 mg/day of urolithin A, a gut-derived “postbiotic” made from compounds in foods like pomegranates and walnuts; the other half took a placebo. Everyone followed the same supervised training, did weekly downhill runs to induce muscle damage, and completed lab tests before and after camp, including VO₂ max, hemoglobin mass, running economy, and a 3,000 m time trial.
Both groups got fitter, but the urolithin A group saw a slightly larger bump in VO₂ max (~5.4% vs. ~3.6%) and a bigger improvement in 3,000 m performance (~2.3% vs. ~0.6%). They also reported lower perceived effort in the post-camp race despite running a bit faster. Muscle-damage markers (creatine kinase) over the 24 hours after the race were clearly lower with urolithin A, suggesting better recovery, even though classic measures of mitochondrial capacity didn’t change over 4 weeks.
Muscle biopsies showed that urolithin A shifted the muscle environment toward better mitochondrial upkeep: more proteins involved in building and maintaining mitochondria, plus signals consistent with increased mitophagy (recycling damaged mitochondria) and slightly damped inflammatory pathways. In plain English, urolithin A seemed to support the quality control side of mitochondrial health rather than giving a quick bump in raw mitochondrial power.
Practical takeaways
Urolothin A is recovery support, not “exercise in a pill.” If you’re heading into a demanding training block—altitude, race-specific work, or heavy downhill/strength phases—urolithin A (around 1,000 mg/day on an empty stomach, as in the study) might help you stack hard sessions with slightly less residual muscle damage and fatigue.
Think food first. Because only ~40% of people are strong natural producers of urolithin A from diet, a supplement guarantees exposure—but pomegranates, certain berries, and walnuts are still a smart, lower-cost play for mitochondrial health and overall nutrition (urolithin A supplements are notoriously expensive).
Save it for when the marginal gains matter. If you’re an older athlete, newer to training, or in a key performance phase, you’re more likely to feel the small edge. If you’re already near your performance ceiling, expect subtle changes in day-to-day readiness rather than huge PRs. Weigh that against the price tag.
What Really Drives VO₂ Max Down with Age?
This paper revisited a classic question: why does VO₂ max fall as we get older? Rather than collecting new data, the authors pooled existing studies of mostly active, healthy men aged ~30–90 years old that reported both VO₂ max and maximal cardiac output. They then used a model of the oxygen cascade—lung to blood to muscle to mitochondria—to separate limitations into two broad buckets:
Central (cardiovascular) resistance: heart and large vessels delivering oxygen.
Peripheral resistance: small vessels, capillaries, muscle fibers, and mitochondria actually extracting and using that oxygen.
Across adulthood, both VO₂ max and cardiac output declined linearly, but not at the same rate. From roughly age 20 to 70, VO₂ max fell by ~46%, while maximal cardiac output dropped by only ~31%. In other words, VO₂ max was falling faster than the heart’s pumping ability, hinting that the muscles and microvasculature were increasingly to blame.
In young adults, the muscles extracted ~80% of the oxygen delivered at max exercise. By ages 75–80, that extraction fraction was down to ~60%. The model suggested that in youth, about 77% of the VO₂ max “bottleneck” is central and 23% peripheral. In older adults, that balance shifts to roughly 56% central and 44% peripheral—peripheral problems almost catch up to the heart as a limiting factor.
Mechanistically, this lines up with what we already know: aging comes with sarcopenia (loss of muscle mass), fewer and less functional mitochondria, lower capillary density, and stiffer, less responsive blood vessels. These changes collectively raise “peripheral resistance” and reduce how much oxygen the muscles can actually use, even when the heart is still doing a decent job.
Practical takeaways
Train both the pump and the pipes. Regular moderate-to-vigorous aerobic exercise supports stroke volume and overall cardiac function, while strength training preserves muscle mass and local “machinery” for oxygen use. Together, they help keep the oxygen cascade low-resistance as we age.
Don’t ignore muscle and mitochondria. Maintaining muscle mass, doing some higher-intensity work (intervals or tempo), and spending time near (or just below) your aerobic “ceiling” are all ways to nudge peripheral adaptations that matter more and more with age.
Accept the unchangeables, optimize the rest. You can’t stop maximal heart rate from drifting down over the decades, but you can keep yourself at the top of your personal curve by staying consistently active rather than repeatedly detraining and restarting.
Inactivity Changes Our Body’s Response to Exercise
This study tested a simple but important question: Does a single low-activity day change how your body responds to exercise the next morning?
Nine healthy, recreationally active young adults completed two conditions in random order. On one day they were forced into near-sedentary living (<5,000 steps, averaging ~3,600). On the other, they were asked to be clearly active (>8,500 steps, averaging ~11,000). The next morning after each day, they did the exact same workout: 60 minutes of cycling at 65% VO₂ max, with blood draws and a muscle biopsy taken before and up to 4 hours after exercise.
On paper, the workouts looked identical. Oxygen uptake, heart rate, workload, calories burned (~650 kcal), and classic blood markers like LDL, HDL, lactate, and free fatty acids were essentially the same, regardless of the previous day’s step count. Subjectively and physiologically, the effort felt similar.
But under the hood, things diverged. After the inactive day, carbohydrate oxidation during the latter part of exercise was higher and fat oxidation lower; blood triglycerides were also higher during exercise and into recovery, suggesting blunted fat handling. The authors point to reduced lipoprotein lipase (LPL) activity and higher muscle glycogen after the low-step day as likely drivers.
At rest, only 9 genes differed between conditions. After exercise, though, more than 1,400 genes changed following the inactive day vs. 793 after the active day (with 397 overlapping). The “extra” genes unique to the inactive condition skewed toward pathways related to immune signaling, growth, senescence, and inflammation—a more “stressed” molecular fingerprint of the same workout.
So the workout still worked in both cases, but when background activity was low, fuel use shifted toward more carbs/less fat, and the muscle’s genomic response looked meaningfully different. This is an early snapshot of “exercise resistance” emerging from everyday inactivity.
Practical takeaways
Separate “training” from “movement.” Hitting structured workouts 4–5 days per week doesn’t fully protect you if you spend the rest of the day mostly sitting. Aim for at least ~8,000–8,500 steps (or several short walks) even on non-training or easy days to keep your muscles metabolically ready for the next session.
Rethink rest days as “active rest.” Good recovery doesn’t mean zero movement. Light walking, easy cycling, or general puttering around the house can help preserve fat-burning capacity and a healthier molecular response to tomorrow’s workout.
Don’t panic about the occasional lazy day. One couch day won’t ruin your adaptations; the problem is when low-step days become the default backdrop to your training. A simple baseline like “never under 7,000 steps unless I’m sick or traveling” is a realistic guardrail and one that I use for myself.
Thanks for reading,
~Brady~