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Surprisingly, optimization using a combination of diet (lower blood glucose and higher blood -hydroxybutyrate), exercise (higher blood lactate), and NAD-related supplementation and modulation of the cytosol-mitochondria NAD-associated reducing equivalents shuttle (hereafter referred to as DEN therapy) increased ATP levels in both neurons and astrocytes toward values of the young metabolic systemcomparable to that of the top-scoring targeted therapy ( Figure 9A

Ciriolo, Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, 00133 Rome, Italy e-mail: [email protected] This article was submitted to Experimental Pharmacology and Drug Discovery, a section of the journal Frontiers in Pharmacology