The role of supraoptic hypothalamic arginine vasopressin neurons in aging-associated water balance and thermoregulatory deficits in male mice.

Authors

Nancy Morones, Predrag Jovanovic, Anna M Sanetra, Kaitlyn Jang, Nareg Keshishian, Zhihan C Cui, Edward Novinbakht, Joshua J Breunig, Anders H Berg, Tamar Pirtskhalava, Selim Chaib, S Ananth Karumanchi, Tamar Tchkonia, Katlin Silm, James L Kirkland, Celine E Riera

Published in

Nature communications. Jun 27, 2026. Epub Jun 27, 2026.

Abstract

Aging disrupts physiological homeostasis, impairing thermoregulation, metabolism, and water balance, but the underlying neural mechanisms remain unclear. Here, we identify arginine vasopressin (AVP) neurons in the supraoptic nucleus (SON) of the hypothalamus as a critical driver of these changes in male mice. Single-nucleus RNA-sequencing revealed Avp among the most upregulated neuronal transcripts with age. Aged SON^AVP neurons displayed enlarged size and heightened excitability, features consistent with hyperactivity. Chemogenetic activation of SON^AVP neurons in young mice reproduced aging-associated phenotypes including hypothermia, reduced energy expenditure, and suppressed water intake. Conversely, knockdown of Avp in the SON of aged mice restored water balance, partially improved thermoregulation and metabolism. Pharmacological studies demonstrated that neuroendocrine AVP signaling mediates these deficits through distinct contributions of V1A and V2 receptors. These findings identify SON^AVP neurons as a central regulator of physiological aging and a potential therapeutic target for age-related homeostatic dysfunction.

PMID:
42364986
Bibliographic data and abstract were imported from PubMed on 28 Jun 2026.

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