Sleep deprivation (SD) is a major health concern in developed countries, especially in the elderly, and is associated with physiological disturbances including cognitive impairment, increased risk of dementia, and leads to the acceleration of neurodegenerative disorders such as Alzheimer’s disease. A logical question is whether cognitive impairment associated with SD can be prevented. To address this question, 22-month-old C57BL/6 mice were sleep deprived during the middle of their sleep cycle for four hours each day for two days. Three days before the SD procedure, treatment was started with the anti-aging peptide glycyl-L-histidyl-L-lysine (GHK) 15 mg/kg per day for five days through the two-day SD procedure. GHK has wound healing and anti-inflammatory properties and readily passes through the blood-brain barrier. Immediately following the last day of SD and GHK treatment, mice were tested for learning impairment using a spatial learning activity which requires them to find the escape hole. Tissues were then collected for neuropathology assessment. Sleep deprived mice treated with GHK consistently found the escape hole more quickly than sleep deprived mice treated with saline suggesting that GHK can prevent the learning impairment associated with short term sleep deprivation. This preliminary observation provides the rationale to investigate the neuro-molecular and neuropathological pathways targeted by GHK including inflammation, oxidative stress and vascular dysfunction.

Diets high in fat and sugar have increasingly adverse effects with increasing age because of generally decreasing activity and energy needs. This nutritional overload results in an increase in body fat mass and an increase in risk for metabolic and cardiovascular disease and possibly other chronic diseases such as cancer. However, the role of fat mass in age-related pathology and survival over an extended period of time is controversial. To address this issue, C57BL/6 mice, 18 months of age, were started on a high caloric (HC) diet consisting of balanced protein, lard, and sucrose. A second cohort was maintained on a standard rodent caloric (RC) diet consisting of balanced protein, wheat, corn, and soybean oil. Fat mass was measured by quantitative magnetic resonance imaging (QMRI) monthly for 10 months (28 months of age) at which time mice were evaluated for physiological performance, and tissues collected for geropathology. Both diet groups started with an average 5 percent fat mass. Fat mass increased to 15 percent in the HC diet group over the next 3-5 months, then gradually decreased to 9 percent after 10 months on the diet. Fat mass gradually decreased to 3 percent in the RC diet group over 10 months. Mice fed the RC diet had increased paw grip strength and were able to stay on a rotating rod longer than mice fed the HC diet, but there was no difference in survival between the two diet cohorts over the 10-month trial period. These preliminary observations suggest that percent body fat mass generated by a diet high in animal fat and table sugar may be associated with unhealthy aging, but not survival. This provides rationale for subsequent investigations into the pathological consequences of high caloric diets with increasing age.