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Age-related changes in murine CNS mRNA gene expression are modulated by dietary melatonin
Edward H Sharman1, Kaizhi G Sharman, Yuan-Wen Ge
1Center for Occupational and Environmental Health, Department of Community and Environmental Medicine, University of California, Irvine, CA 92697, USA. esharman@uci.edu
Abstract:
Brain cellular functions decline with normal aging, accompanied by a changing profile of gene expression. Gene array analysis was used to quantitatively estimate messenger RNA (mRNA) expression levels in the cerebral cortex of both young (4-month) and old (27-month) B6C3F1 male mice. A stringent degree of significance was obtained by using multiple gene chips. Out of 12,423 mRNA levels, only 25 changed significantly with age. Nine of these genes coded for inflammatory proteins, all of which were elevated in aged, relative to younger mice. Melatonin (200 p.p.m.) included in the diet of aged animals for 8 wk elevated serum and cortical melatonin and reversed 13 of the 25 genes altered with age. In no case did melatonin potentiate age-related changes in gene expression. The restoration of a more youthful gene profile to brains of aged animals by melatonin, to a large extent, involves reversal of age-induced elevation of basal inflammatory parameters.
Insights
Aging brains show altered gene expression, with increased inflammation. Melatonin supplementation in aged mice reversed many age-related gene changes, reducing inflammation and restoring a more youthful gene profile.
Area of Science:
- Neuroscience
- Molecular Biology
- Gerontology
Background:
- Normal aging leads to a decline in brain cellular functions and altered gene expression patterns.
- Specific changes in messenger RNA (mRNA) levels in the cerebral cortex are associated with aging.
Purpose of the Study:
- To investigate age-related changes in gene expression in the mouse brain.
- To determine the effect of melatonin supplementation on age-altered gene expression and brain inflammation.
Main Methods:
- Gene array analysis was employed to quantify mRNA expression levels in the cerebral cortex of young and aged B6C3F1 male mice.
- Aged mice received melatonin (200 p.p.m.) in their diet for 8 weeks.
- Changes in gene expression and serum/cortical melatonin levels were analyzed.
Main Results:
- Out of 12,423 mRNA levels, only 25 showed significant age-related changes.
- Nine of these differentially expressed genes were associated with inflammatory proteins, elevated in aged mice.
- Melatonin treatment reversed 13 of the 25 age-altered genes and reduced age-induced elevation of inflammatory parameters.
Conclusions:
- Melatonin supplementation can restore a more youthful gene expression profile in the aging brain.
- The beneficial effects of melatonin in aged brains are largely due to the reversal of age-induced inflammation.
- Melatonin does not potentiate age-related gene expression changes.
