In older adults with frailty or sarcopenia, exercise reduces TNF-α but has no effect on IL-6 or CRP, indicating that the inflammatory cascade in these conditions is resistant to modulation beyond TNF-α.

When older adults with muscle loss exercise, their muscles contract and produce less harmful stress chemicals, which turns off a key inflammation switch inside muscle and fat cells. This switch, when off, stops the production of TNF-α, a major inflammation signal. Exercise also shrinks fat tissue that normally pumps out TNF-α, and reduces damage signals from weakened muscle, which calms down immune cells that would otherwise make more TNF-α. This process lowers TNF-α in the blood but does not affect later inflammation signals like IL-6 or CRP because those are driven by other sources, like aging cells that keep releasing them no matter what.