Aging is a fundamental biological process that is influenced by a number of genetic and environmental factors. Oxidative damage to macromolecules, including protein, lipid and nucleic acid, is thought to be one of the causative factors of aging. A commonly used biomarker of protein oxidative damages is the formation of protein carbonyl, ketone and/or aldehyde groups. Accurate and sensitive measurement of the protein carbonyl level is critical for us to understanding the aging process. However, the accuracy of current analytical techniques, including mass spectrometry, fluorescence, and immunoassay based methods, is limited for applications where small changes in the protein modification level are of biological significance. To address this issue, we have collaborated with Dr. Dongmao Zhang at Mississippi State University to develop a novel ratiometric Raman spectroscopic (RMRS) method for quantitative determination of the protein carbonyl level. This method utilizes the unique spectrum of protein in the sample as the internal control, which results in significantly improved accuracy for comparing the difference in the protein carbonyl level among samples. The findings have been published in Analytical Chemistry. This study provides a foundation for us to further investigate molecular changes in the aging process and consequences of these alterations on lifespan and healthspan. A robust environmental manipulation of lifespan is dietary restriction (DR), which has been shown to extend lifespan in many species, ranging from invertebrates to mammals. However, it would be challenging to impose long-term DR in humans. An alternative strategy would be to apply pharmaceutical or nutraceutical compounds to induce responses that would mimic DR. A few compounds have been shown to have this effect in model organisms. However, the number is still small and little is known about mechanisms by which these compounds extend lifespan. Dietary supplements are widely used with the belief that they can forestall disease and increase longevity. Few systematic attempts have been made to confirm prolongevity claims made or to investigate potentially effective interventions. We have developed several prolongevity screen systems and have assessed the effects of more than a dozen of compounds on lifespan in the mexfly. This screen has been conducted in the Moscafrut mass-rearing facility at Tapachula, Chiapas, Mexico. We have published some of our results from this study in Experimental Gerontology showing that resveratrol, a polyphenolic compound, can extend lifespan of the mexflies only under certain nutritional conditions, suggesting the prolongevity effect of resveratrol depends on dietary composition and content. Consumption of cranberry has been shown to have numerous health benefits, especially on fighting against urinary tract infection. However, not much is known about anti-aging effects of cranberry. Considering that cranberry is rich in polyphenolics, we postulate that cranberry has anti-aging properties. To test this hypothesis, we have investigated the prolongevity and anti-aging effects of cranberry supplementation both in rats and mexfly. We have found that long-term supplementation of cranberry can delay some age-related decline of physiological functions, including glucose metabolism. We have also found that cranberry supplementation can modulate the lifespan of mexflies in a dietary composition and sex dependent manner. Two manuscripts describing these results have been submitted for review in scientific journals. These findings encourages us to further investigate health benefits and molecular mechanisms of cranberry consumption related to aging, which will provide scientific guidance to cranberry consumption. In summary, we have addressed several central issues related to aging. We have developed an analytic tool to accurately and reliably measure molecular changes in aging. We have employed mexflies to search for effective aging interventions, which will be further assessed in rodents. These studies should prove valuable to advance the objective of Laboratory of Experimental Gerontology to investigate and develop aging interventions in mammals. Identification of the conserved features in aging and prolongevity interventions are clearly valuable for understanding human aging and more importantly for developing effective aging intervention strategies for humans.
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