The liver-produced enzyme GPLD1, released during exercise, can restore memory function in aged brains by modulating brain blood vessels rather than requiring physical activity itself. This enzyme works by cleaving tissue-nonspecific alkaline phosphatase (TNAP) on cerebral blood vessels, which normally accumulates with age and impairs the blood-brain barrier's transport functions. When researchers artificially increased TNAP levels in young mice, it mimicked age-related cognitive decline, while blocking TNAP in older animals restored youthful brain gene expression patterns and memory performance. This discovery illuminates why exercise benefits cognition even in sedentary individuals who receive blood transfusions from active donors. The liver-to-brain communication pathway represents a paradigm shift from viewing exercise benefits as purely activity-dependent to understanding them as transferable biochemical signals. For aging adults, this suggests that pharmaceutical mimicking of GPLD1 or TNAP inhibition could potentially deliver cognitive protection without requiring intense physical exercise. The research also demonstrated efficacy in Alzheimer's models, where both GPLD1 enhancement and TNAP blocking reduced amyloid pathology. However, translation to humans requires careful validation, as the mouse vascular system may not perfectly mirror human cerebrovascular aging patterns.