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- Title
Quantification of localized NAD<sup>+</sup> changes reveals unique specificity of NAD<sup>+</sup> regulation in the hypothalamus.
- Authors
Johnson, Sean; Yoshioka, Kiyoshi; Brace, Cynthia S.; Imai, Shin-ichiro
- Abstract
Recently, it has become a consensus that systemic decreases in NAD+ are a critical trigger for age-associated functional decline in multiple tissues and organs. The hypothalamus, which contains several functionally distinct subregions called nuclei, functions as a high-order control center of aging in mammals. However, due to a technical difficulty, how NAD+ levels change locally in each hypothalamic nucleus during aging remains uninvestigated. We were able to establish a new combinatorial methodology, using laser-captured microdissection (LCM) and high-performance liquid chromatography (HPLC), to accurately measure NAD+ levels in small tissue samples. We applied this methodology to examine local NAD+ changes in hypothalamic nuclei and found that NAD+ levels were decreased significantly in the arcuate nucleus (ARC), ventromedial hypothalamus (VMH), and lateral hypothalamus (LH), but not in the dorsomedial hypothalamus (DMH) of 22-month-old mice, compared to those of 3-month-old mice. The administration of nicotinamide mononucleotide (NMN) significantly increased NAD+ levels in all these hypothalamic nuclei. Interestingly, the administration of extracellular nicotinamide phosphoribosyltransferase-containing extracellular vesicles (eNampt-EVs) purified from young mice increased NAD+ levels in the ARC and DMH. These results reveal the unique specificity of NAD+ regulation in the hypothalamus during aging.
- Subjects
NUCLEOTIDE metabolism; HYPOTHALAMUS anatomy; HIGH performance liquid chromatography; ANIMAL experimentation; COENZYMES; HYPOTHALAMUS; TRANSFERASES; AGING; SENSITIVITY &; specificity (Statistics); MICE; EXTRACELLULAR vesicles; ANALYTICAL chemistry; METABOLISM; EVALUATION
- Publication
NPJ Aging, 2023, Vol 9, Issue 1, p1
- ISSN
2731-6068
- Publication type
Article
- DOI
10.1038/s41514-023-00098-1