3.9 Article

Ageing restructures the transcriptome of the hypothalamic supraoptic nucleus and alters the response to dehydration

Journal

NPJ AGING
Volume 9, Issue 1, Pages -

Publisher

NATURE PUBL GROUP
DOI: 10.1038/s41514-023-00108-2

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Ageing leads to altered neuroendocrine function, particularly in the hypothalamic supraoptic nucleus, resulting in changes in acute responses to hyperosmotic cues and increased susceptibility to dehydration in the elderly. Vasopressin, the hormone produced by this nucleus, has been associated with age-related diseases like type 2 diabetes and metabolic syndrome. A study using gene analysis techniques found that ageing is linked to changes in the expression of extracellular matrix genes in the supraoptic nucleus. Interestingly, while the overall transcriptomic response to dehydration is diminished in aged animals compared to adults, specific genes related to neurodegenerative processes are enriched in the aged rats, suggesting that dehydration may trigger degenerative consequences in older individuals.
Ageing is associated with altered neuroendocrine function. In the context of the hypothalamic supraoptic nucleus, which makes the antidiuretic hormone vasopressin, ageing alters acute responses to hyperosmotic cues, rendering the elderly more susceptible to dehydration. Chronically, vasopressin has been associated with numerous diseases of old age, including type 2 diabetes and metabolic syndrome. Bulk RNAseq transcriptome analysis has been used to catalogue the polyadenylated supraoptic nucleus transcriptomes of adult (3 months) and aged (18 months) rats in basal euhydrated and stimulated dehydrated conditions. Gene ontology and Weighted Correlation Network Analysis revealed that ageing is associated with alterations in the expression of extracellular matrix genes. Interestingly, whilst the transcriptomic response to dehydration is overall blunted in aged animals compared to adults, there is a specific enrichment of differentially expressed genes related to neurodegenerative processes in the aged cohort, suggesting that dehydration itself may provoke degenerative consequences in aged rats.

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