Sleeping Flies

How is sleep controlled?  Selection for fruit flied with long or short time sleep periods demonstrates the importance of certain key signaling pathways; this tells us why it is difficult to ascertain “the meaning of sleep,” because these pathways of cell signaling have so many different effects. Abstract:

Why do some individuals need more sleep than others? Forward mutagenesis screens in flies using engineered mutations have established a clear genetic component to sleep duration, revealing mutants that convey very long or short sleep. Whether such extreme long or short sleep could exist in natural populations was unknown. We applied artificial selection for high and low night sleep duration to an outbred population of Drosophila melanogaster for 13 generations. At the end of the selection procedure, night sleep duration diverged by 9.97 hours in the long and short sleeper populations, and 24-hour sleep was reduced to 3.3 hours in the short sleepers. Neither long nor short sleeper lifespan differed appreciably from controls, suggesting little physiological consequences to being an extreme long or short sleeper. Whole genome sequence data from seven generations of selection revealed several hundred thousand changes in allele frequencies at polymorphic loci across the genome. Combining the data from long and short sleeper populations across generations in a logistic regression implicated 126 polymorphisms in 80 candidate genes, and we confirmed three of these genes and a larger genomic region with mutant and chromosomal deficiency tests, respectively. Many of these genes could be connected in a single network based on previously known physical and genetic interactions. Candidate genes have known roles in several classic, highly conserved developmental and signaling pathways-EGFR, Wnt, Hippo, and MAPK. The involvement of highly pleiotropic pathway genes suggests that sleep duration in natural populations can be influenced by a wide variety of biological processes, which may be why the purpose of sleep has been so elusive.

Mitochondria And Aging: Fruit Flies...And Perhaps Humans As Well

By André Karwath aka Aka - Own work, CC BY-SA 2.5, https://commons.wikimedia.org/w/index.php?curid=227170

The mitochondria are the “powerhouses” of the cell, and problems with mitochondria and mitochondrial function have been associated with a number of diseases and disorders. Increased levels of dysfunctional mitochondria have been linked to aging, and this study linked here shows that “middle-aged” Drosophila (fruit flies) tend to have more elongated, dysfunctional mitochondria. Upregulation if a gene called Drp-1 promotes fission of those aberrant mitochondria, which in turn enhances mitophagy (in simple terms: cellular “clean-up” of the dysfunctional mitochondria) and enhanced mitochondrial function.  This in turn has anti-aging effects in the flies. Now, the objective here is not to improve the health of aging fruit flies (which may or may not be a worthy goal on its own, depending on your perspective), but to apply these findings to the human case, and to see how further investigation into these findings can inform us about ant-aging strategies in humans. This is the basic science-human health link on full display.  Abstract:

The accumulation of dysfunctional mitochondria has been implicated in aging, but a deeper understanding of mitochondrial dynamics and mitophagy during aging is missing. Here, we show that upregulating Drp1-a Dynamin-related protein that promotes mitochondrial fission-in midlife, prolongs Drosophila lifespan and healthspan. We find that short-term induction of Drp1, in midlife, is sufficient to improve organismal health and prolong lifespan, and observe a midlife shift toward a more elongated mitochondrial morphology, which is linked to the accumulation of dysfunctional mitochondria in aged flight muscle. Promoting Drp1-mediated mitochondrial fission, in midlife, facilitates mitophagy and improves both mitochondrial respiratory function and proteostasis in aged flies. Finally, we show that autophagy is required for the anti-aging effects of midlife Drp1-mediated mitochondrial fission. Our findings indicate that interventions that promote mitochondrial fission could delay the onset of pathology and mortality in mammals when applied in midlife. Mitochondrial fission and fusion are important mechanisms to maintain mitochondrial function. Here, the authors report that middle-aged flies have more elongated, or 'hyper-fused' mitochondria, and show that induction of mitochondrial fission in midlife, but not in early life, extends the health and life of flies.