Chronic inhibition of mammalian target of rapamycin by rapamycin modulates cognitive and non-cognitive components of behavior throughout lifespan in mice.

Aging is, by far, the greatest risk factor for most neurodegenerative diseases. In non-diseased conditions, normal aging can also be associated with declines in cognitive function that significantly affect quality of life in the elderly. It was recently shown that inhibition of Mammalian TOR (mTOR) activity in mice by chronic rapamycin treatment extends lifespan, possibly by delaying aging {Harrison, 2009 #4}{Miller, 2011 #168}. To explore the effect of chronic rapamycin treatment on normal brain aging we determined cognitive and non-cognitive components of behavior throughout lifespan in male and female C57BL/6 mice that were fed control- or rapamycin-supplemented chow. Our studies show that rapamycin enhances cognitive function in young adult mice and blocks age-associated cognitive decline in older animals. In addition, mice fed with rapamycin-supplemented chow showed decreased anxiety and depressive-like behavior at all ages tested. Levels of three major monoamines (norepinephrine, dopamine and 5-hydroxytryptamine) and their metabolites (3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindolacetic acid) were significantly augmented in midbrain of rapamycin-treated mice compared to controls. Our results suggest that chronic, partial inhibition of mTOR by oral rapamycin enhances learning and memory in young adults, maintains memory in old C57BL/6J mice, and has concomitant anxiolytic and antidepressant-like effects, possibly by stimulating major monoamine pathways in brain.

The relationship of parental alcoholism and family dysfunction to stress among college students.

The relationship between collegiate adult children of alcoholics (ACOAs) and adult children from dysfunctional families (ACDFs) was examined to determine whether ACOAs and ACDFs were at greater risk of stress than non-ACOAs and non-ACDFs. The participants were 549 students from a midwestern university. The data collection instruments were the Children of Alcoholics Screening Test, 6-Item Version (CAST-6); the Family Adaptability and Cohesion Evaluation Scales, Version II (FACES-II); and the Perceived Stress Scale (PSS). A substantial proportion of the sample was classified as ACOA, ACDF, or both, and there was considerable overlap between the two groups. Both ACOA and ACDF status were found to be significant predictors of stress, with ACDF status being a better predictor than ACOA status. Possible explanations for the results and implications for collegiate wellness programs are discussed.

Mammalian aging, metabolism, and ecology: evidence from the bats and marsupials.

This study compared trends in body size, life span, metabolic rate, and ecology of bats and marsupials with those from mammals generally, using a 580 species data base. The linear logarithmic relationship between mammalian body mass and maximum longevity, deleting bats and marsupials, is used as a standard against which to measure life spans of particular mammal groups. Bats have maximum life spans a minimum of 3 times those of nonflying eutherians--a trend resulting from neither low basal metabolic rate, the ability to enter torpor, nor large relative brain size. Marsupials live about 80% as long as nonflying eutherians despite averaging lower basal metabolic rates; similarly, there is no effect of heterothermy or relative brain size. These results directly conflict with predictions of both "rate of living" and brain-size mediated theories of aging. However, they are consistent with an evolutionary theory that posits exceptionally long life spans among mammals with reduced environmental vulnerability.