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cofactor · 3
Joint cartilage has no blood vessels and tendons have very little blood supply, so both depend heavily on load for nourishment and repair: cartilage exchanges nutrients as it is squeezed and released, and tendons need load to stimulate collagen synthesis. For them, long rest is not protection but decline; the signal that triggers repair is the load itself.
When muscles contract, they can move glucose into cells without insulin, through the glucose transporter GLUT4. That is why a walk after a meal flattens the blood glucose curve, and it is the mechanism behind calling walking a medicine.
Regular strength training is often underrated here: it preserves muscle and improves metabolic health, which are the exact opposites of the factors that push testosterone down, such as obesity and poor metabolic health. It is not a testosterone-boosting program; it is fixing the foundation.
regulates · 6
In the Cooney 2013 Cochrane review, exercise compared with no treatment or a control condition had a moderate pooled effect; in only the most rigorously designed trials, however, the effect was much smaller and no longer significant. So exercise helps with depression and can be considered alongside therapy and medication, but it cannot be called as strong as drugs. Myokines and brain-derived neurotrophic factor (BDNF) are candidate mechanisms still under study, not settled ones.
When muscle contracts, a signal called AMPK moves the glucose transporter GLUT4 to the cell membrane without needing insulin. In the DPP trial (Knowler 2002), the lifestyle group, aiming to lose weight and exercise at least 150 minutes a week, cut its risk of developing type 2 diabetes by 58%, against 31% for metformin; that was the combined effect of diet, weight loss and exercise. In Reynolds 2016, a crossover trial in type 2 diabetes, a 10-minute walk after each of three meals lowered post-meal blood sugar more than a single 30-minute walk at another time.
Aerobic exercise gives the most reliable drop in blood pressure in people whose pressure is high (Cornelissen 2013, pooling 93 trials). Isometric exercise works too, such as squeezing a handgrip or holding a wall sit: Smart 2019, pooling each participant's data across trials, found systolic pressure fell by about 6.9 mmHg and diastolic by about 3.9 mmHg on average, similar to the average effect of a single blood-pressure drug.
Kredlow 2015 pooled dozens of studies: a single workout gave only small benefits for sleep, while regular exercise kept up for several weeks gave larger ones, cutting the time to fall asleep by about 13 minutes on average and improving total sleep time and how well people felt they slept. On timing, only one point is fairly certain: hard exercise right before bed may delay sleep.
The Liu 2009 Cochrane review pooled 121 randomized trials in older adults: progressive strength training clearly increased strength (standardized mean difference 0.84, a large effect) and improved walking speed, rising from a chair and stair climbing. No drug is approved specifically to treat sarcopenia; strength training plus enough protein is the main answer.
The interleukin 6 (IL-6) released by contracting muscle is not the same signal as the IL-6 that visceral fat releases chronically: the contraction kind suppresses tumor necrosis factor (TNF-alpha) and raises anti-inflammatory factors such as IL-10. That is how regular exercise pushes down the baseline of inflammaging while preserving muscle.
Mechanism · One IL-6, two signals
The IL-6 released by contracting muscle is not the same signal as the IL-6 that lingers in visceral fat. The contraction kind suppresses TNF-alpha and raises IL-10 and the IL-1 receptor antagonist, so its effect is anti-inflammatory. Pedersen and Febbraio 2008 describe muscle as an endocrine organ. Regular exercise pushes down the baseline of inflammaging while preserving muscle, breaking the cycle in which inflammation and muscle loss worsen each other.
Evidence · What this review establishes
What this review establishes is the identity of the signal: IL-6 from contracting muscle differs from IL-6 from fat. It gives no prescription for minutes of exercise per week and no timetable for inflammatory markers after a session. What you can take away is the direction: muscle contraction itself sends an anti-inflammatory signal; only regular exercise over time shifts the baseline, and one hard workout is not a medicine.
Background · What exercise cannot replace
Exercise does not replace vaccines and is not an anti-inflammatory drug; vaccination in older adults still follows the schedule for their age. This is only about the path through muscle-derived signals. Keeping muscle also takes enough protein. And a rise in IL-6 from one bout of exercise should not be read as reversing the shrinking of the thymus.