scholarly journals iPLA2-VIA is required for healthy aging in neurons, muscle, and female germline in Drosophila melanogaster

2021 ◽  
Author(s):  
Surya Banerjee ◽  
Adina Schonbrun ◽  
Sogol Eizadshenass ◽  
Shimshon Benji ◽  
Yaakov Tzvi Cantor ◽  
...  

AbstractNeurodegenerative disease (ND) is a growing health burden worldwide, but its causes and treatments remain elusive. Although most cases of ND are sporadic, rare familial cases have been attributed to single genes, which can be investigated in animal models. We have generated a new mutation in the calcium-independent phospholipase A2 (iPLA2) VIA gene CG6718, the Drosophila melanogaster ortholog of human PLA2G6/PARK14, mutations in which cause a suite of NDs collectively called PLA2G6-associated neurodegeneration (PLAN). Our mutants display age-related loss of climbing ability, a symptom of neurodegeneration in flies. Although phospholipase activity commonly is presumed to underlie iPLA2-VIA function, locomotor decline in our mutants is rescued by a transgene carrying a serine-to-alanine mutation in the catalytic residue, suggesting that important functional aspects are independent of phospholipase activity. Additionally, we find that iPLA2-VIA knockdown in either muscle or neurons phenocopies locomotor decline with age, demonstrating its necessity in both neuronal and non-neuronal tissues. Furthermore, RNA in situ hybridization shows high endogenous iPLA2-VIA mRNA expression in adult germ cells, and transgenic HA-tagged iPLA2-VIA colocalizes with mitochondria there. Mutant males are fertile with normal spermatogenesis, while fertility is reduced in mutant females. Mutant female germ cells display age-related mitochondrial aggregation, loss of mitochondrial potential, and elevated cell death. These results suggest that iPLA2-VIA is important for germline mitochondrial integrity in Drosophila, which may be relevant for understanding how PLAN develops.

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0256738
Author(s):  
Surya Jyoti Banerjee ◽  
Adina Schonbrun ◽  
Sogol Eizadshenass ◽  
Shimshon Benji ◽  
Yaakov Tzvi Cantor ◽  
...  

Neurodegenerative disease (ND) is a growing health burden worldwide, but its causes and treatments remain elusive. Although most cases of ND are sporadic, rare familial cases have been attributed to single genes, which can be investigated in animal models. We have generated a new mutation in the calcium-independent phospholipase A2 (iPLA2) VIA gene CG6718, the Drosophila melanogaster ortholog of human PLA2G6/PARK14, mutations in which cause a suite of NDs collectively called PLA2G6-associated neurodegeneration (PLAN). Our mutants display age-related loss of climbing ability, a symptom of neurodegeneration in flies. Although phospholipase activity commonly is presumed to underlie iPLA2-VIA function, locomotor decline in our mutants is rescued by a transgene carrying a serine-to-alanine mutation in the catalytic residue, suggesting that important functional aspects are independent of phospholipase activity. Additionally, we find that iPLA2-VIA knockdown in either muscle or neurons phenocopies locomotor decline with age, demonstrating its necessity in both neuronal and non-neuronal tissues. Furthermore, RNA in situ hybridization shows high endogenous iPLA2-VIA mRNA expression in adult germ cells, and transgenic HA-tagged iPLA2-VIA colocalizes with mitochondria there. Mutant males are fertile with normal spermatogenesis, while fertility is reduced in mutant females. Mutant female germ cells display age-related mitochondrial aggregation, loss of mitochondrial potential, and elevated cell death. These results suggest that iPLA2-VIA is critical for mitochondrial integrity in the Drosophila female germline, which may provide a novel context to investigate its functions with parallels to PLAN.


Genetics ◽  
2002 ◽  
Vol 160 (2) ◽  
pp. 537-545
Author(s):  
Justen Andrews ◽  
Brian Oliver

Abstract Nonautonomous inductive signals from the soma and autonomous signals due to a 2X karyotype determine the sex of Drosophila melanogaster germ cells. These two signals have partially overlapping influences on downstream sex determination genes. The upstream OVO-B transcription factor is required for the viability of 2X germ cells, regardless of sexual identity, and for female germline sexual identity. The influence of inductive and autonomous signals on ovo expression has been controversial. We show that ovo-B is strongly expressed in the 2X germ cells in either a male or a female soma. This indicates that a 2X karyotype controls ovo-B expression in the absence of inductive signals from the female soma. However, we also show that female inductive signals positively regulate ovo-B transcription in the 1X germ cells that do not require ovo-B function. Genetic analysis clearly indicates that inductive signals from the soma are not required for ovo-B function in 2X germ cells. Thus, while somatic inductive signals and chromosome karyotype have overlapping regulatory influences, a 2X karyotype is a critical germline autonomous determinant of ovo-B function in the germline.


Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 121
Author(s):  
Kadine Cabey ◽  
Dani M. Long ◽  
Alexander Law ◽  
Nora E. Gray ◽  
Christine McClure ◽  
...  

Due to an increase in the aging population, age-related diseases and age-related changes, such as diminished cognition and sleep disturbances, are an increasing health threat. It has been suggested that an increase in oxidative stress underlies many of these changes. Current treatments for these diseases and changes either have low efficacy or have deleterious side effects preventing long-time use. Therefore, alternative treatments that promote healthy aging and provide resilience against these health threats are needed. The herbs Withania somnifera and Centella asiatica may be two such alternatives because both have been connected with reducing oxidative stress and could therefore ameliorate age-related impairments. To test the effects of these herbs on behavioral phenotypes induced by oxidative stress, we used the Drosophila melanogaster sniffer mutant which has high levels of oxidative stress due to reduced carbonyl reductase activity. Effects on cognition and mobility were assessed using phototaxis assays and both, W. somnifera and C. asiatica water extracts improved phototaxis in sniffer mutants. In addition, W. somnifera improved nighttime sleep in male and female sniffer flies and promoted a less fragmented sleep pattern in male sniffer flies. This suggests that W. somnifera and C. asiatica can ameliorate oxidative stress-related changes in behavior and that by doing so they might promote healthy aging in humans.


Genetics ◽  
2002 ◽  
Vol 161 (1) ◽  
pp. 195-204 ◽  
Author(s):  
Michael J Simmons ◽  
Kevin J Haley ◽  
Craig D Grimes ◽  
John D Raymond ◽  
Jarad B Niemi

Abstract Drosophila were genetically transformed with a hobo transgene that contains a terminally truncated but otherwise complete P element fused to the promoter from the Drosophila hsp70 gene. Insertions of this H(hsp/CP) transgene on either of the major autosomes produced the P transposase in both the male and female germlines, but not in the soma. Heat-shock treatments significantly increased transposase activity in the female germline; in the male germline, these treatments had little effect. The transposase activity of two insertions of the H(hsp/CP) transgene was not significantly greater than their separate activities, and one insertion of this transgene reduced the transposase activity of P(ry+, Δ2-3)99B, a stable P transgene, in the germline as well as in the soma. These observations suggest that, through alternate splicing, the H(hsp/CP) transgene produces a repressor that feeds back negatively to regulate transposase expression or function in both the somatic and germline tissues. The H(hsp/CP) transgenes are able to induce gonadal dysgenesis when the transposase they encode has P-element targets to attack. However, this ability and the ability to induce P-element excisions are repressed by the P cytotype, a chromosomal/cytoplasmic state that regulates P elements in the germline.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Manjot Kaur Grewal ◽  
Shruti Chandra ◽  
Alan Bird ◽  
Glen Jeffery ◽  
Sobha Sivaprasad

AbstractTo evaluate the effect of aging, intra- and intersession repeatability and regional scotopic sensitivities in healthy and age-related macular degeneration (AMD) eyes. Intra- and intersession agreement and effect of age was measured in healthy individuals. The mean sensitivity (MS) and pointwise retinal sensitivities (PWS) within the central 24° with 505 nm (cyan) and 625 nm (red) stimuli were evaluated in 50 individuals (11 healthy and 39 AMD eyes). The overall intra- and intersession had excellent reliability (intraclass correlation coefficient, ICC > 0.90) and tests were highly correlated (Spearman rs = 0.75–0.86). Eyes with subretinal drusenoid deposit (SDD) had reduced PWS centrally, particularly at inferior and nasal retinal locations compared with controls and intermediate AMD (iAMD) without SDD. There was no difference in MS or PWS at any retinal location between iAMD without SDD and healthy individuals nor between iAMD with SDD and non-foveal atrophic AMD groups. Eyes with SDD have reduced rod function compared to iAMD without SDD and healthy eyes, but similar to eyes with non-foveal atrophy. Our results highlight rod dysfunction is not directly correlated with drusen load and SDD location.


Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1409
Author(s):  
Barbara Strasser ◽  
Dominik Pesta ◽  
Jörn Rittweger ◽  
Johannes Burtscher ◽  
Martin Burtscher

Regular physical exercise and a healthy diet are major determinants of a healthy lifespan. Although aging is associated with declining endurance performance and muscle function, these components can favorably be modified by regular physical activity and especially by exercise training at all ages in both sexes. In addition, age-related changes in body composition and metabolism, which affect even highly trained masters athletes, can in part be compensated for by higher exercise metabolic efficiency in active individuals. Accordingly, masters athletes are often considered as a role model for healthy aging and their physical capacities are an impressive example of what is possible in aging individuals. In the present review, we first discuss physiological changes, performance and trainability of older athletes with a focus on sex differences. Second, we describe the most important hormonal alterations occurring during aging pertaining regulation of appetite, glucose homeostasis and energy expenditure and the modulatory role of exercise training. The third part highlights nutritional aspects that may support health and physical performance for older athletes. Key nutrition-related concerns include the need for adequate energy and protein intake for preventing low bone and muscle mass and a higher demand for specific nutrients (e.g., vitamin D and probiotics) that may reduce the infection burden in masters athletes. Fourth, we present important research findings on the association between exercise, nutrition and the microbiota, which represents a rapidly developing field in sports nutrition.


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