SWITCHBOX

Switchbox: Maintaining health in old age through homeostasis

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 Obiettivo del progetto (Objective)

'Healthy aging requires maintenance of homeostatic control of the physiological systems and functions that are integrated by the hypothalamus. Driven by work in previous EU projects (Crescendo/Lifespan) highlighting insulin signalling and the hypothalamic/pituitary/adrenal and thyroid axes in the regulation of aging, SWITCHBOX will examine the flexibility of these neuroendocrine systems in response to environmental challenges in three established human cohorts with variable aging potential. These human cohorts include offspring of exceptionally long-lived siblings and their partners (controls), people with good vs bad cognitive performance or with high vs low cognitive engagement. Maintaining brain function is emphasised as it reflects an individual’s overall well-being, a major goal in aging research, and because age-related brain disorders represent a major socioeconomic burden. To determine the genetic and cellular underpinnings of the findings in humans, hypothesis-based studies in rodents sharing phenotypes with the human cohorts will be carried out. To clarify the role of the brain in the differential regulation of endocrine axes critical for healthy aging, SWITCHBOX will examine the neuroendocrine and metabolic effects of intranasal (humans) and intra-cerebroventricular (rodents) administration of peptides involved in controlling metabolic homeostasis (e.g. insulin, α-MSH). State-of-the-art technology will be used to measure circadian endocrine and metabolic profiles, brain structure and function (fMRI) and cognitive performance, as well as cellular and molecular features. All data will be entered into an already operational ‘open access’ database. The work aims to take key findings from basic research and translate them into clinically relevant concepts. It will benefit from combining expertise of gerontologists, endocrinologists, molecular and cellular neuroscientists and neuropsychologists. SWITCHBOX ultimately aims to develop conceptually new approaches for the prevention and treatment of age-related disorders.'

Introduzione (Teaser)

Given Europe's burgeoning senior citizen population, research on healthy ageing is pressing and calls for new approaches. EU funding is helping one consortium tackle the topic in the context of brain/metabolism regulated by endocrine function.

Descrizione progetto (Article)

The 'Switchbox' project: Maintaining health in old age through homeostasis' has been set up to examine the flexibility of certain neuroendocrine systems as related to environmental challenges and the control of metabolic homeostasis. Efforts centre on clarifying the role of the brain in the differential regulation of endocrine axes identified as critical to healthy ageing. This approach builds on evidence that the dysregulation of relevant homeostatic mechanisms is associated with increased morbidity and impairments in brain function.

With current consensus holding that brain and metabolic and endocrine processes are bi-directionally linked, Switchbox partners intend to facilitate healthy ageing by improving our understanding and exploitation of homeostatic mechanisms. The focus on metabolic homeostasis aims at promoting ways to regulate both metabolic and mental health.

An overall strategy has been designed that shifts the focus of current ageing studies in humans and in animals. By establishing protocols for human and rodent studies, collecting baseline data on human cohorts and establishing animal colonies for the parallel rodent studies, Switchbox is now in a position to determine interactions between metabolic and mental health. The parallel use of rodent models and humancohorts allows experimental testingin rodents of hypotheses generated by human studies.

To this end, partners have been trained on the use of the MIND ageing database that compiles all the human data collected, and preliminary experimental challenges, in rodents and humans, have been carried out to compare homeostatic flexibility within and across cohorts. Robust predictive variables are being identified by analysing multimodal endpoints across certain cohorts, the project's data on endocrine measures was complemented by neuro-functional and neuro-structural analyses (brain imaging). Other project accomplishments to date include analysingresulting data with a variety of appropriate statistical tools to derive factors that could improve the prediction of healthy ageing or cognitive performance.

Continuing work ultimately aims to generate results translatable into clinically relevant concepts. The establishment of a central repository for multiple data sets on human and rodent ageing has the potential for short- and longer-term impacts across fields. It will also prove useful for deriving algorithms for healthy ageing and informing healthy ageing networks and key stakeholder groups.