Yet, the molecular pathways through which sleep deprivation wreaks its detrimental effects on the body remain poorly understood. Although numerous studies have looked at the consequences of sleep deprivation on the brain, comparatively few have directly tested its effects on peripheral organs.
There is increased ER stress in the pancreas of aged mice. Phosphorylation of PERK (P-PERK), indicative of ER stress and activation of the unfolded protein response, is evident in ß-cells. Representative images of P-PERK (green) in B-cells (red) immunostained for insulin in young undisturbed (YC), young SD (YSD), old undisturbed (OC) and old sleep deprived (OSD) mice.
Credit: Nirinjini Naidoo, Ph.D., Division of Sleep Medicine: Perelman School of Medicine; Aging Cell
During sleep deprivation cells upregulate the UPR – the unfolded protein response – a process where misfolded proteins get refolded or degraded.
Five years ago, researchers at the Perelman School of Medicine, University of Pennsylvania, showed that the UPR is an adaptive response to stress induced by sleep deprivation and is impaired in the brains of old mice. Those findings suggested that inadequate sleep in the elderly, who normally experience sleep disturbances, could exacerbate an already-impaired protective response to protein misfolding that happens in aging cells. Protein misfolding and clumping is associated with many diseases such as Alzheimer's and Parkinson's, noted Nirinjini Naidoo, Ph.D., research associate professor in the Division of Sleep Medicine in that study.
Naidoo is also senior author of a follow-up study in Aging Cell this month that shows, for the first time, an effect of sleep deprivation on the UPR in peripheral tissue, in this case, the pancreas. They showed that stress in pancreatic cells due to sleep deprivation may contribute to the loss or dysfunction of these cells important to maintaining proper blood sugar levels, and that these functions may be exacerbated by normal aging.
"The combined effect of aging and sleep deprivation resulted in a loss of control of blood sugar reminiscent of pre-diabetes in mice," says Naidoo. "We hypothesize that older humans might be especially susceptible to the effects of sleep deprivation on the disruption of glucose homeostasis via cell stress."
Working with Penn colleague Joe Baur, Ph.D., assistant professor of Physiology, Naidoo started a collaboration to look at the relationship of sleep deprivation, the UPR, and metabolic response with age. Other researchers had suggested that the death of beta cells associated with type 2 diabetes may be due to stress in a cell compartment called the endoplasmic reticulum (ER). The UPR is one part of the quality control system in the ER, where some proteins are made.
Knowing this, Naidoo and Baur asked if sleep deprivation (SD) causes ER stress in the pancreas, via an increase in protein misfolding, and in turn, how this relates to aging.
The team examined tissues in mice for cellular stress following acute SD, and they also looked for cellular stress in aging mice. Their results show that both age and SD combine to induce cellular stress in the pancreas.
Older mice fared markedly worse when subjected to sleep deprivation. Pancreas tissue from older mice or from young animals subjected to sleep deprivation exhibited signs of protein misfolding, yet both were able to maintain insulin secretion and control blood sugar levels. Pancreas tissue from acutely sleep-deprived aged animals exhibited a marked increase in CHOP, a protein associated with cell death, suggesting a maladaptive response to cellular stress with age that was amplified by sleep deprivation.
Acute sleep deprivation caused increased plasma glucose levels in both young and old animals. However, this change was not overtly related to stress in beta cells, since plasma insulin levels were not lower following acute lack of sleep.
Accordingly, young animals subjected to acute sleep deprivation remained tolerant to a glucose challenge. In a chronic sleep deprivation experiment, young mice were sensitized to insulin and had improved control of their blood sugar, whereas aged animals became hyperglycemic and failed to maintain appropriate plasma insulin concentrations.
While changes in insulin secretion are unlikely to play a major role in the acute effects of SD, cellular stress in pancreatic tissue suggests that chronic SD may contribute to the loss or dysfunction of endocrine cells, and that these effects may be exacerbated by normal aging, say the researchers.
This study was supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases (DK19525) and the National Institute on Aging (AG23500), and the Ellison Medical Foundation. Baur is also a member of the Institute for Diabetes, Obesity, and Metabolism at Penn.
This work was also sponsored by the Center for Sleep and Circadian Neurobiology (CSCN) at Penn and Naidoo is a member of the CSCN.
Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.
The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 16 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $398 million awarded in the 2012 fiscal year.
The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; Chester County Hospital; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2012, Penn Medicine provided $827 million to benefit our community.
Karen Kreeger | EurekAlert!
First time-lapse footage of cell activity during limb regeneration
25.10.2016 | eLife
Phenotype at the push of a button
25.10.2016 | Institut für Pflanzenbiochemie
Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.
This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...
Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion
Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
26.10.2016 | Power and Electrical Engineering
26.10.2016 | Awards Funding
26.10.2016 | Power and Electrical Engineering