TY - JOUR
T1 - Sleep disorders, obesity, and aging
T2 - The role of orexin
AU - Nixon, Joshua P.
AU - Mavanji, Vijayakumar
AU - Butterick, Tammy A.
AU - Billington, Charles J
AU - Kotz, Catherine M
AU - Teske, Jennifer A.
N1 - Publisher Copyright:
© 2014.
PY - 2015/3/1
Y1 - 2015/3/1
N2 - The hypothalamic neuropeptides orexin A and B (hypocretin 1 and 2) are important homeostatic mediators of central control of energy metabolism and maintenance of sleep/wake states. Dysregulation or loss of orexin signaling has been linked to narcolepsy, obesity, and age-related disorders. In this review, we present an overview of our current understanding of orexin function, focusing on sleep disorders, energy balance, and aging, in both rodents and humans. We first discuss animal models used in studies of obesity and sleep, including loss of function using transgenic or viral-mediated approaches, gain of function models using exogenous delivery of orexin receptor agonist, and naturally-occurring models in which orexin responsiveness varies by individual. We next explore rodent models of orexin in aging, presenting evidence that orexin loss contributes to age-related changes in sleep and energy balance. In the next section, we focus on clinical importance of orexin in human obesity, sleep, and aging. We include discussion of orexin loss in narcolepsy and potential importance of orexin in insomnia, correlations between animal and human studies of age-related decline, and evidence for orexin involvement in age-related changes in cognitive performance. Finally, we present a summary of recent studies of orexin in neurodegenerative disease. We conclude that orexin acts as an integrative homeostatic signal influencing numerous brain regions, and that this pivotal role results in potential dysregulation of multiple physiological processes when orexin signaling is disrupted or lost.
AB - The hypothalamic neuropeptides orexin A and B (hypocretin 1 and 2) are important homeostatic mediators of central control of energy metabolism and maintenance of sleep/wake states. Dysregulation or loss of orexin signaling has been linked to narcolepsy, obesity, and age-related disorders. In this review, we present an overview of our current understanding of orexin function, focusing on sleep disorders, energy balance, and aging, in both rodents and humans. We first discuss animal models used in studies of obesity and sleep, including loss of function using transgenic or viral-mediated approaches, gain of function models using exogenous delivery of orexin receptor agonist, and naturally-occurring models in which orexin responsiveness varies by individual. We next explore rodent models of orexin in aging, presenting evidence that orexin loss contributes to age-related changes in sleep and energy balance. In the next section, we focus on clinical importance of orexin in human obesity, sleep, and aging. We include discussion of orexin loss in narcolepsy and potential importance of orexin in insomnia, correlations between animal and human studies of age-related decline, and evidence for orexin involvement in age-related changes in cognitive performance. Finally, we present a summary of recent studies of orexin in neurodegenerative disease. We conclude that orexin acts as an integrative homeostatic signal influencing numerous brain regions, and that this pivotal role results in potential dysregulation of multiple physiological processes when orexin signaling is disrupted or lost.
KW - Aging
KW - Energy balance
KW - Hypocretin
KW - Obesity
KW - Orexin
KW - Sleep
UR - http://www.scopus.com/inward/record.url?scp=84923350841&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84923350841&partnerID=8YFLogxK
U2 - 10.1016/j.arr.2014.11.001
DO - 10.1016/j.arr.2014.11.001
M3 - Review article
C2 - 25462194
AN - SCOPUS:84923350841
SN - 1568-1637
VL - 20
SP - 63
EP - 73
JO - Ageing Research Reviews
JF - Ageing Research Reviews
ER -