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I.R.F. / News / General / 02090401

Aging and Gene Expression in Brain
Posted on: September 4, 2002

Brain Although the molecular basis of aging remains unknown, a large body of evidence indicates that oxidative stress results in DNA damage that subsequently leads to changes in gene expression and organismal aging. Genetic modifications or spontaneous mutations in a variety of organisms that result in oxidative stress resistance increase longevity. In Caenorhabditis elegans, the reduction of metabolic rate through genetic manipulation or environmental changes increases life span. Dietary restriction also delays the aging process and extends life span, possibly by lowering metabolic rate and thus reducing the production of reactive oxygen species. The hypothalamus plays a key role in regulating metabolism. Consequently, an understanding of the effects of aging on the hypothalamus may provide important insights into the organismal aging process. For example, it has been shown that neuroendocrine regulation of insulin signaling affects longevity in C. elegans. In mammals, hypothalamic modulation of the neuroendocrine system may regulate the aging process by controlling the production, processing, and degradation of neuroendocrine hormones and neuropeptides. To better understand the molecular processes involved in aging, changes in gene expression in the aged hypothalamus were examined. To determine whether these age-associated gene expression changes are tissue specific, gene expression in the cortex of young and aged mice was measured. Results demonstrated that the expression levels of many genes related to neuronal signaling, plasticity, and structure were changed in the aged brain. Moreover, many proteases were up-regulated during the aging process in both hypothalamus and cortex, a number of which are involved in the processing and degradation of neuropeptides. Altered expression of these genes may contribute to age-related disorders of synaptic plasticity and memory storage, neurodegenerative diseases, and normal organismal aging.

Aging leads to the misregulation of many proteins involved in neuronal signaling and structure that may be associated with the age-related phenotype and diseases. In addition, alterations in protease levels likely play an important role in the aging brain as well as having a broader effect on the neuroendocrine system. Additional experiments to determine which of these changes are primary-cause factors in age-related brain dysfunction may provide new insights into the aging process and new approaches to the development of therapeutic agents.

Source: Yinghe HU et al (2001). Full article please find in www.pnas.org
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