Falling Short: The Contribution of Central Insulin Receptors to Gait Dysregulation in Brain Aging

Sami L. Case, Hilaree N. Frazier, Katie L. Anderson, Ruei Lung Lin, Olivier Thibault

Research output: Contribution to journalReview articlepeer-review

Abstract

Insulin resistance, which manifests as a reduction of insulin receptor signaling, is known to correlate with pathological changes in peripheral tissues as well as in the brain. Central insulin resistance has been associated with impaired cognitive performance, decreased neuronal health, and reduced brain metabolism; however, the mechanisms underlying central insulin resistance and its impact on brain regions outside of those associated with cognition remain unclear. Falls are a leading cause of both fatal and non-fatal injuries in the older population. Despite this, there is a paucity of work focused on age-dependent alterations in brain regions associated with ambulatory control or potential therapeutic approaches to target these processes. Here, we discuss age-dependent alterations in central modalities that may contribute to gait dysregulation, summarize current data supporting the role of insulin signaling in the brain, and highlight key findings that suggest insulin receptor sensitivity may be preserved in the aged brain. Finally, we present novel results showing that administration of insulin to the somatosensory cortex of aged animals can alter neuronal communication, cerebral blood flow, and the motivation to ambulate, emphasizing the need for further investigations of intranasal insulin as a clinical management strategy in the older population.

Original languageEnglish
Article number1923
JournalBiomedicines
Volume10
Issue number8
DOIs
StatePublished - Aug 2022

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health (R01AG033649 to O.T. and T32AG057461 to H.N.F.).

Publisher Copyright:
© 2022 by the authors.

Keywords

  • ambulatory function
  • gerontology
  • insulin resistance
  • signaling

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology (all)

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