INFLUENCE OF AGE ON 7-DEHYDROCHOLESTEROL IN THE SKIN

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The goals of our research program are to define how aging affects the capacity of human skin to provide adequate vitamin D nutrition and to determine whether aging affects the responsiveness of the skin to the active form of vitamin D, 1,25-dihydroxyvitamin D. We have developed the technology and the expertise to (a) synthesis radiolabeled 7-dehydrocholesterol, (b) chromatographically separate 7-dehydrocholesterol from its photoproducts and cholesterol, (c) culture human keratinocytes, and (d) conduct human studies to quantitatively determine the effect of exposure to ultraviolet radiation on the vitamin D endocrine system. During the next 5 years of this grant we plan, in a methodical fashion, to (a) determine the mechanism(s) responsible for the age-dependent decrease in epidermal 7-dehydrocholesterol stores, (b) evaluate whether aging affects the responsiveness of human keratinocytes to respond to 1,25-(OH)2-D3, (c) examine the effect that aging has on the ability of human volunteers to raise circulating concentrations of vitamin D in response to exposure to ultraviolet radiation, (d) determine how much surface area of the body needs to be exposed to solar radiation in order to provide adequate vitamin D nutrition, (e) determine whether a single long exposure or multiple short exposures to UV radiation has the same effect on the vitamin D endocrine system, and (f) determine what effect changes in latitude has on the capacity of the skin to produce vitamin D3. Results from this research should provide basic new insights about how aging affects the capacity of human skin to produce vitamin D3 and to provide valuable new information about how the elderly can use the natural resource of the sun to provide them with adequate vitamin D nutrition when dietary sources are inadequate.