Lactate-driven mitochondrial pretenders hijack hippocampal function after excessive exercise.

Larsen, Filip J · Cell Metab · 2026

rct · Level II

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Abstract

Huang et al.<sup>1</sup> show a J-shaped relationship between vigorous activity and cognitive decline, with maximal benefit ∼1,000-1,300 MET-min/week and harm with excessive exercise. Using UK Biobank data, mechanistic models, and an RCT, they implicate lactate-driven mitochondria-derived vesicles that reach the hippocampus, disrupt synapses, and impair cognition.

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