Disturbed phospholipid metabolism in serine biosynthesis defects revealed by metabolomic profiling.

Serine biosynthesis defects are autosomal recessive metabolic disorders resulting from the deficiency of any of the three enzymes involved in de novo serine biosynthesis, specifically phosphoglycerate dehydrogenase (PGDH), phosphoserine aminotransferase (PSAT), and phosphoserine phosphatase (PSP). In this study, we performed metabolomic profiling on 4 children with serine biosynthesis defects; 3 with PGDH deficiency and 1 with PSAT deficiency. The evaluations were performed at baseline and with serine and glycine supplementation.

Multi-species data integration and gene ranking enrich significant results in an alcoholism genome-wide association study.

Background: A variety of species and experimental designs have been used to study genetic influences on alcohol dependence, ethanol response, and related traits. Integration of these heterogeneous data can be used to produce a ranked target gene list for additional investigation.

Results: In this study, we performed a unique multi-species evidence-based data integration using three microarray experiments in mice or humans that generated an initial alcohol dependence (AD) related genes list, human linkage and association results, and gene sets implicated in C.

Smith-Magenis syndrome results in disruption of CLOCK gene transcription and reveals an integral role for RAI1 in the maintenance of circadian rhythmicity.

Haploinsufficiency of RAI1 results in Smith-Magenis syndrome (SMS), a disorder characterized by intellectual disability, multiple congenital anomalies, obesity, neurobehavioral abnormalities, and a disrupted circadian sleep-wake pattern. An inverted melatonin rhythm (i.e.

Reduced mitochondrial SOD displays mortality characteristics reminiscent of natural aging.

Manganese superoxide dismutase (MnSOD or SOD2) is a key mitochondrial enzymatic antioxidant. Arguably the most striking phenotype associated with complete loss of SOD2 in flies and mice is shortened life span. To further explore the role of SOD2 in protecting animals from aging and age-associated pathology, we generated a unique collection of Drosophila mutants that progressively reduce SOD2 expression and function.

Dietary restriction alters demographic but not behavioral aging in Drosophila.

Dietary restriction extends lifespan substantially in numerous species including Drosophila. However, it is unclear whether dietary restriction in flies impacts age-related functional declines in conjunction with its effects on lifespan. Here, we address this issue by assessing the effect of dietary restriction on lifespan and behavioral senescence in two wild-type strains, in our standard white laboratory stock, and in short-lived flies with reduced expression of superoxide dismutase 2.

Distinct genetic influences on locomotor senescence in Drosophila revealed by a series of metrical analyses.

Decline of locomotor function is a prominent feature of aging in most species. We previously described a series of metrical analyses for quantifying functional declines associated with aging. Here, we have applied these metrics to elucidate differences in the nature of locomotor senescence between Drosophila cohorts from four different genetic backgrounds (Canton-S, Oregon-R, Samarkand and Lausanne-S) and two long-lived mutant strains, Indy(206) and chico(1).

Behavioral responses to odorants in drosophila require nervous system expression of the beta integrin gene myospheroid.

Integrins are cell adhesion molecules that mediate numerous developmental processes in addition to a variety of acute physiological events. Two reports implicate a Drosophila beta integrin, betaPS, in olfactory behavior. To further investigate the role of integrins in Drosophila olfaction, we used Gal4-driven expression of RNA interference (RNAi) transgenes to knock down expression of myospheroid (mys), the gene that encodes betaPS.

Oxidative damage and age-related functional declines.

Most organisms experience progressive declines in physiological function as they age. Since this senescence of function is thought to underlie the decrease in quality of life in addition to the increase in susceptibility to disease and death associated with aging, identifying the mechanisms involved would be highly beneficial. One of the leading mechanistic theories for aging is the oxidative damage hypothesis.

Functional senescence in Drosophila melanogaster.

The fruit fly Drosophila melanogaster is one of the principal model organisms used for studying the biology of aging. Flies are well suited for such studies for a number of reasons. Flies develop to adulthood quickly, have a relatively short life span, and are inexpensive to house.

A proposed set of descriptors for functional senescence data.

Declines in function are common manifestations of aging in many phyla. Because functional senescence is thought to drive the increasing risk of death with age, understanding functional senescence is important for understanding aging. Experimental investigation of functional senescence requires one to quantitative and compare age-dependent declines in function between cohorts.

Rapid iterative negative geotaxis (RING): a new method for assessing age-related locomotor decline in Drosophila.

Age-related behavioral declines are common manifestations of aging in animals. Negative geotaxis, an innate escape response during which flies ascend the wall of a cylinder after being tapped to its bottom, is one of the behaviors that senesces in Drosophila. Many laboratories, including ours, have used a variety of negative geotaxis assays based on the performance of single flies.

Dissociation between functional senescence and oxidative stress resistance in Drosophila.

Many studies strongly suggest a causal link between oxidative stress and determination of life span. The relationship between oxidative stress and age-related functional declines, however, is less clear. Additionally, the full spectrum of functional declines associated with aging has not been systematically evaluated in the fruit fly, Drosophila melanogaster, one of the leading models for aging research.