Age-Related Dysfunction of Water Homeostasis
Dehydration can be an issue in older people. As in every complex system in the body, the mechanisms by which hydration is regulated become dysfunctional with advancing age. Researchers here look at the brain region responsible for regulating some of the response to dehydration, cataloging altered gene expression in search of the more important mechanisms involved in the vulnerability of old people to harmful levels of dehydration.
Ageing is accompanied by an increased prevalence of disorders of body salt and water composition. As revealed by the UK Dehydration Recognition In Our Elders (DRIE), 20% of residents in care are dehydrated. Many elderly patients admitted to the hospital present osmotic balance disorders, and dehydration (DH) is often a cause of morbidity and mortality in senior citizens. Thus, to improve healthy living among the elderly, we need to understand why salt and water imbalances occur in this age group. Both peripheral and central mechanisms controlling salt and water homoeostasis change with age. Ageing is accompanied by a gradual decline in renal function, with urine-concentrating capacities reduced in the elderly compared to younger subjects. This diminished ability to conserve bodily water, accompanied by reduced thirst and insufficient water intake after fluid deprivation, makes the elderly more prone to DH.
Ageing is associated with altered neuroendocrine function. In the context of the hypothalamic supraoptic nucleus (SON), which makes the antidiuretic hormone arginine 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.
We compared the transcriptomes of the SON in adult and aged euhydrated rats and found massive changes in gene expression associated with ageing, including genes involved in extracellular matrix (ECM) organisation and cell adhesion. It is known that the SON has a complex and dynamic ECM that has been implicated in its physiological functioning. The transcriptomic response to dehydration is overall blunted in aged animals compared to adults, and 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.
Dysfunctional water homoeostasis in ageing is associated with the inappropriate release of the antidiuretic hormone arginine vasopressin (AVP). The capabilities of the AVP system to respond to osmotic stress decrease with age. In the aged animal, the capacity of the AVP system to respond to dehydration is attenuated. These deficits may be associated with dysfunction in mechanisms controlling transcription, mRNA stability, or translation. Indeed, we have previously shown that the steady-state response to dehydration of a number of selected gene transcripts is attenuated in aged animals. This appears to be a transcriptome level effect, with many of the common genes regulated by dehydration showing a blunted response in aged animals compared to adults. This generalised attenuation of the transcriptomic response to dehydration is likely to greatly affect SON function and overall osmoregulatory effectiveness.