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1.
Evolution ; 77(8): 1780-1790, 2023 07 27.
Article in English | MEDLINE | ID: mdl-37195902

ABSTRACT

Evolutionary theory assumes that mutations that cause aging either have beneficial early-life effects that gradually become deleterious with advancing age (antagonistic pleiotropy [AP]) or that they only have deleterious effects at old age (mutation accumulation [MA]). Mechanistically, aging is predicted to result from damage accumulating in the soma. While this scenario is compatible with AP, it is not immediately obvious how damage would accumulate under MA. In a modified version of the MA theory, it has been suggested that mutations with weakly deleterious effects at young age can also contribute to aging, if they generate damage that gradually accumulates with age. Mutations with increasing deleterious effects have recently gained support from theoretical work and studies of large-effect mutations. Here we address if spontaneous mutations also have negative effects that increase with age. We accumulate mutations with early-life effects in Drosophila melanogaster across 27 generations and compare their relative effects on fecundity early and late in life. Our mutation accumulation lines on average have substantially lower early-life fecundity compared to controls. These effects were further maintained throughout life, but they did not increase with age. Our results suggest that most spontaneous mutations do not contribute to damage accumulation and aging.


Subject(s)
Aging , Drosophila melanogaster , Animals , Drosophila melanogaster/genetics , Aging/genetics , Mutation , Mutation Accumulation , Age Factors
2.
Proc Biol Sci ; 289(1980): 20221115, 2022 08 10.
Article in English | MEDLINE | ID: mdl-35946149

ABSTRACT

General evolutionary theory predicts that individuals in low condition should invest less in sexual traits compared to individuals in high condition. Whether this positive association between condition and investment also holds between young (high condition) and senesced (low condition) individuals is however less clear, since elevated investment into reproduction may be beneficial when individuals approach the end of their life. To address how investment into sexual traits changes with age, we study genes with sex-biased expression in the brain, the tissue from which sexual behaviours are directed. Across two distinct populations of Drosophila melanogaster, we find that old brains display fewer sex-biased genes, and that expression of both male-biased and female-biased genes converges towards a sexually intermediate phenotype owing to changes in both sexes with age. We further find that sex-biased genes in general show heightened age-dependent expression in comparison to unbiased genes and that age-related changes in the sexual brain transcriptome are commonly larger in males than females. Our results hence show that ageing causes a desexualization of the fruit fly brain transcriptome and that this change mirrors the general prediction that low condition individuals should invest less in sexual phenotypes.


Subject(s)
Drosophila , Transcriptome , Aging , Animals , Brain , Drosophila/genetics , Drosophila melanogaster/genetics , Drosophila melanogaster/metabolism , Female , Male , Sex Characteristics
3.
Exp Cell Res ; 317(14): 2052-8, 2011 Aug 15.
Article in English | MEDLINE | ID: mdl-21565190

ABSTRACT

Gold nanoparticles are recently having much attention because of their increased applications in biomedical fields. In this paper, we demonstrated the photothermal efficacy of citrate capped gold nanoparticles (AuNPs) for the destruction of A431 cancer cells. Citrate capped AuNPs were synthesized successfully and characterized by UV-visible-NIR spectrophotometry and High Resolution Transmission Electron Microscopy (HR-TEM). Further, AuNPs were conjugated with epidermal growth factor receptor antibody (anti-EGFR) and applied for the selective photothermal therapy (PTT) of human epithelial cancer cells, A431. PTT experiments were conducted in four groups, Group I--control cells, Group II--cells treated with laser light alone, Group III--cells treated with unconjugated AuNP and further laser irradiation and Group IV--anti-EGFR conjugated AuNP treated cells irradiated by laser light. After laser irradiation, cell morphology changes that were examined using phase contrast microscopy along with the relevant biochemical parameters like lactate dehydrogenase activity, reactive oxygen species generation and caspase-3 activity were studied for all the groups to determine whether cell death occurs due to necrosis or apoptosis. From these results we concluded that, these immunotargeted nanoparticles could selectively induce cell death via ROS mediated apoptosis when cells were exposed to a low power laser light.


Subject(s)
Citric Acid/pharmacology , Gold/pharmacology , Laser Therapy , Lasers , Metal Nanoparticles/chemistry , Neoplasms/therapy , Antibodies, Monoclonal/pharmacology , Citric Acid/chemistry , Epithelial Cells/drug effects , Epithelial Cells/pathology , Gold/chemistry , Humans , Neoplasms/pathology , Tumor Cells, Cultured
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