Biomedical subjects
Publications and source records attributed to Ted Brummel.
We researched the lifespan of Drosophila under axenic conditions compared with customary procedure. The experiments revealed that the presence of bacteria during the first week of adult life can enhance lifespan, despite unchanged food intake. Later in life, the presence of bacteria can reduce lifespan. Certain long-lived mutants react in different ways, indicating an interplay between bacteria and longevity-enhancing genes.
Functional analyses of changes in the immune response indicate that aging is associated with a decline of adaptive immunity whereas innate immunity is ramped up. Gene expression studies also support age-dependent changes in immunity. Studies using a large panel of methodologies and multiple species show that some of the most dramatic transcriptional changes that occur during aging are associated with immunity. This observation leads to two fundamental questions: (1) Why is the immune response altered with age? (2) Is this a consequence of aging or does it contribute to it? The origin of these changes and the mechanistic relationship among them as well as with aging must be identified. In mammals, this task is complicated by the interdependence of the innate and adaptive immune systems. The value of invertebrates as model organisms to help answer these questions is presented. This includes a description of the immune response in invertebrate models and how it compares with vertebrates, focusing on conserved pathways. Finally, these questions are explored in light of recent reports and data from our laboratory. Experimental alterations of longevity indicate that the differential expression of immunity-related genes during aging is linked to the rate of aging. Long-lived nematodes are more resistant to pathogens and blocking the expression of immune-related genes can prevent lifespan extension. These observations suggest that the immune response has a positive effect on longevity, possibly by increasing fitness. By contrast, it has been reported that activation of the immune system can reduce longevity upon starvation. We also observed that deregulation of the immune response has drastic effects on viability and longevity in Drosophila. These data suggest that the immune response results in a trade-off between beneficial and detrimental effects that might profoundly affect the aging process. Given this, immunity may be an ally early in life, but turns out to be an enemy as we age.
The relationship between gene expression and the regulation of longevity is poorly understood. Previous studies focusing on microarray or tissue-specific changes in gene expression as a function of age have provided evidence that gene expression is a dynamic process which is regulated, even late in an organism's lifespan. Using the enhancer-trap technique, a systematic analysis of the spatio-temporal regulation of gene expression in tissues of adult Drosophila is presented. As many as 80% of enhancer traps analysed displayed (some form of) transcriptional change with age. In some cases the rate of change in expression was found to correlate with changes in longevity under various conditions, suggesting that they may be indicators of 'physiological age' and therefore valuable markers for dissecting the aging process. Molecular analysis of enhancer traps that showed increased activity with age was performed to identify candidate genes that may be important in the regulation of longevity; we identified changes in reporters associated with immunity, microtubule organization and muscle function.