scholarly journals Contrasting effects of aging on the expression of transposons, the piRNA machinery and mitochondrial transcripts in the Drosophila ovary

2018 ◽  
Author(s):  
Alexandra A. Erwin ◽  
Justin P. Blumenstiel

ABSTRACTRedistribution of heterochromatin during aging has been linked to the de-repression of transposable elements and an overall loss of gene regulation in the soma. Whether or not epigenetic factors such as heterochromatin marks are perturbed in reproductive and germline tissues is of particular interest because some epigenetic factors are known to transmit across generations. Additionally, the relative contribution of factors intrinsic or extrinsic to the germ line have in reproductive decline remains unknown. Using mRNA sequencing data from late stage egg chambers in Drosophila melanogaster, we show that age-related expression changes occur in genes residing in heterochromatin, particularly on the largely heterochromatic 4th chromosome. In addition, we identify an increase in expression of the piRNA machinery. We further identify a striking age-related reduction in mitochondrial transcripts that we can attribute to the somatic tissues. Other than a modest increase in overall TE expression in the aging germline, we find no global TE de-repression in reproductive tissues. Rather, the observed effects of aging on TEs are primarily strain and family specific. These results indicate unique responses in somatic versus germline tissue with regards to epigenetic aging effects and suggest that the global loss of TE control observed in other studies may be specific to certain tissues, genetic backgrounds and TE family. This study also demonstrates that while age-related effects can be maternally transmitted, the germline is generally robust to age-related changes.

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Lilit Nersisyan ◽  
◽  
Maria Nikoghosyan ◽  
Arsen Arakelyan

AbstractTelomere length (TL) regulation is an important factor in ageing, reproduction and cancer development. Genetic, hereditary and environmental factors regulating TL are currently widely investigated, however, their relative contribution to TL variability is still understudied. We have used whole genome sequencing data of 250 family trios from the Genome of the Netherlands project to perform computational measurement of TL and a series of regression and genome-wide association analyses to reveal TL inheritance patterns and associated genetic factors. Our results confirm that TL is a largely heritable trait, primarily with mother’s, and, to a lesser extent, with father’s TL having the strongest influence on the offspring. In this cohort, mother’s, but not father’s age at conception was positively linked to offspring TL. Age-related TL attrition of 40 bp/year had relatively small influence on TL variability. Finally, we have identified TL-associated variations in ribonuclease reductase catalytic subunit M1 (RRM1 gene), which is known to regulate telomere maintenance in yeast. We also highlight the importance of multivariate approach and the limitations of existing tools for the analysis of TL as a polygenic heritable quantitative trait.


Nature Aging ◽  
2021 ◽  
Author(s):  
Steve Horvath ◽  
Amin Haghani ◽  
Nicholas Macoretta ◽  
Julia Ablaeva ◽  
Joseph A. Zoller ◽  
...  

AbstractNaked mole rats (NMRs) live an exceptionally long life, appear not to exhibit age-related decline in physiological capacity and are resistant to age-related diseases. However, it has been unknown whether NMRs also evade aging according to a primary hallmark of aging: epigenetic changes. To address this question, we profiled n = 385 samples from 11 tissue types at loci that are highly conserved between mammalian species using a custom array (HorvathMammalMethylChip40). We observed strong epigenetic aging effects and developed seven highly accurate epigenetic clocks for several tissues (pan-tissue, blood, kidney, liver, skin clocks) and two dual-species (human–NMR) clocks. The skin clock correctly estimated induced pluripotent stem cells derived from NMR fibroblasts to be of prenatal age. The NMR epigenetic clocks revealed that breeding NMR queens age more slowly than nonbreeders, a feature that is also observed in some eusocial insects. Our results show that despite a phenotype of negligible senescence, the NMR ages epigenetically.


2013 ◽  
Vol 109 (7) ◽  
pp. 1852-1865 ◽  
Author(s):  
Tara K. Jacobson ◽  
Matthew D. Howe ◽  
Brandy Schmidt ◽  
James R. Hinman ◽  
Monty A. Escabí ◽  
...  

Hippocampal theta and gamma oscillations coordinate the timing of multiple inputs to hippocampal neurons and have been linked to information processing and the dynamics of encoding and retrieval. One major influence on hippocampal rhythmicity is from cholinergic afferents. In both humans and rodents, aging is linked to impairments in hippocampus-dependent function along with degradation of cholinergic function. Cholinomimetics can reverse some age-related memory impairments and modulate oscillations in the hippocampus. Therefore, one would expect corresponding changes in these oscillations and possible rescue with the cholinomimetic physostigmine. Hippocampal activity was recorded while animals explored a familiar or a novel maze configuration. Reexposure to a familiar situation resulted in minimal aging effects or changes in theta or gamma oscillations. In contrast, exploration of a novel maze configuration increased theta power; this was greater in adult than old animals, although the deficit was reversed with physostigmine. In contrast to the theta results, the effects of novelty, age, and/or physostigmine on gamma were relatively weak. Unrelated to the behavioral situation were an age-related decrease in the degree of theta-gamma coupling and the fact that physostigmine lowered the frequency of theta in both adult and old animals. The results indicate that age-related changes in gamma and theta modulation of gamma, while reflecting aging changes in hippocampal circuitry, seem less related to aging changes in information processing. In contrast, the data support a role for theta and the cholinergic system in encoding and that hippocampal aging is related to impaired encoding of new information.


2018 ◽  
Vol 9 (1) ◽  
pp. 61-66 ◽  
Author(s):  
Ali K. Bourisly ◽  
Ali Shuaib

Abstract Age-related effects were studied in 14 younger (M = 34 years) and 14 (M = 47 years) older healthy participants. Event-related potential (ERP) recording was done using a 256-channel EEG system. Results indicated that ERP is affected by advanced age. There was a significant difference in P200 mean latency between the younger participants and older participants for the target (low-probability) stimuli, but no such significance was evident for the P200 mean latency during the presentation of the standard (high-probability) stimuli. As for the P200 mean peak amplitude, the results for the target (low-probability) stimuli did show a significant difference between the two age groups, while the results for the standard (high-probability) stimuli did not show any significant difference between the two age groups. The results of this study are explained in light of aging effects on attentional recruitment and frontal lobe intactness.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christoph Kirch ◽  
Leonardo L. Gollo

AbstractAging is a main risk factor for neurodegenerative disorders including Alzheimer's disease. It is often accompanied by reduced cognitive functions, gray-matter volume, and dendritic integrity. Although age-related brain structural changes have been observed across multiple scales, their functional implications remain largely unknown. Here we simulate the aging effects on neuronal morphology as dendritic pruning and characterize its dynamical implications. Utilizing a detailed computational modeling approach, we simulate the dynamics of digitally reconstructed neurons obtained from Neuromorpho.org. We show that dendritic pruning affects neuronal integrity: firing rate is reduced, causing a reduction in energy consumption, energy efficiency, and dynamic range. Pruned neurons require less energy but their function is often impaired, which can explain the diminished ability to distinguish between similar experiences (pattern separation) in older people. Our measures indicate that the resilience of neuronal dynamics is neuron-specific, heterogeneous, and strongly affected by dendritic topology and the position of the soma. Based on the emergent neuronal dynamics, we propose to classify the effects of dendritic deterioration, and put forward a topological measure of “neuronal reserve” that quantifies the resilience of neuronal dynamics to dendritic pruning. Moreover, our findings suggest that increasing dendritic excitability could partially mitigate the dynamical effects of aging.


Proceedings ◽  
2020 ◽  
Vol 61 (1) ◽  
pp. 25
Author(s):  
Lluïsa Miró ◽  
Miquel Moretó ◽  
Concepció Amat ◽  
Javier Polo ◽  
Anna Pérez-Bosque

We have studied the effects of aging on the fecal microbiota composition in the senescence-accelerated prone mice SAMP8 strain. We compared animals two, four, and six months old. Feces were collected at the end of each period and a genomic study was carried out on fecal DNA using the Illumina MiSeq analyzer. The Shannon diversity index showed similar values along this period and the number of species was neither affected by aging. The phylum Verrucobacteria went up with age, showing a seven-fold increase at six months, compared to two-month old mice. At the family level, changes observed between two and six months of age involved significant increases in Bacteroidaceae (q < 0.001) and strong reductions in Lactobacillaceae (q < 0.0001) and Prevotellaceae (q < 0.05); at the genus level, there was a significant reduction in probiotic Lactobacillus. At the species level, we observed an age-related reduction in Lactobacillus hayakitensis, a species involved in mucosal immune homeostasis, and in Blautia hansenii, which provides protection against Clostridium difficile infection. Interestingly, aging increases Parabacteroides goldsteiini, which is involved in the regulation of the TLR4 pathway. These results support the view that aging results in the proliferation of bacterial species that are associated with the immune deterioration of the gut mucosa.


2020 ◽  
Vol 29 (3) ◽  
pp. 391-403
Author(s):  
Dania Rishiq ◽  
Ashley Harkrider ◽  
Cary Springer ◽  
Mark Hedrick

Purpose The main purpose of this study was to evaluate aging effects on the predominantly subcortical (brainstem) encoding of the second-formant frequency transition, an essential acoustic cue for perceiving place of articulation. Method Synthetic consonant–vowel syllables varying in second-formant onset frequency (i.e., /ba/, /da/, and /ga/ stimuli) were used to elicit speech-evoked auditory brainstem responses (speech-ABRs) in 16 young adults ( M age = 21 years) and 11 older adults ( M age = 59 years). Repeated-measures mixed-model analyses of variance were performed on the latencies and amplitudes of the speech-ABR peaks. Fixed factors were phoneme (repeated measures on three levels: /b/ vs. /d/ vs. /g/) and age (two levels: young vs. older). Results Speech-ABR differences were observed between the two groups (young vs. older adults). Specifically, older listeners showed generalized amplitude reductions for onset and major peaks. Significant Phoneme × Group interactions were not observed. Conclusions Results showed aging effects in speech-ABR amplitudes that may reflect diminished subcortical encoding of consonants in older listeners. These aging effects were not phoneme dependent as observed using the statistical methods of this study.


Author(s):  
Elisa M. Trucco ◽  
Gabriel L. Schlomer ◽  
Brian M. Hicks

Approximately 48–66% of the variation in alcohol use disorders is heritable. This chapter provides an overview of the genetic influences that contribute to alcohol use disorder within a developmental perspective. Namely, risk for problematic alcohol use is framed as a function of age-related changes in the relative contribution of genetic and environmental factors and an end state of developmental processes. This chapter discusses the role of development in the association between genes and the environment on risk for alcohol use disorder. Designs used to identify genetic factors relevant to problematic alcohol use are discussed. Studies examining developmental pathways to alcohol use disorder with a focus on endophenotypes and intermediate phenotypes are reviewed. Finally, areas for further investigation are offered.


Amino Acids ◽  
2021 ◽  
Author(s):  
Tomohisa Yoshimura ◽  
Yuki Inokuchi ◽  
Chikako Mutou ◽  
Takanobu Sakurai ◽  
Tohru Nagahama ◽  
...  

AbstractTaurine, a sulfur-containing amino acid, occurs at high concentrations in the skin, and plays a role in maintaining the homeostasis of the skin. We investigated the effects of aging on the content and localization of taurine in the skin of mice and rats. Taurine was extracted from the skin samples of hairless mice and Sprague Dawley rats, and the taurine content of the skin was determined by high-performance liquid chromatography (HPLC). The results of the investigation revealed that the taurine content in both the dermis and epidermis of hairless mice declined significantly with age. Similar age-related decline in the skin taurine content was also observed in rats. In contrast, the taurine content in the sole remained unchanged with age. An immunohistochemical analysis also revealed a decreased skin taurine content in aged animals compared with younger animals, although no significant differences in the localization of taurine were observed between the two age groups. Supplementation of the drinking water of aged mice with 3% (w/v) taurine for 4 weeks increased the taurine content of the epidermis, but not the dermis. The present study showed for the first time that the taurine content of the skin decreased with age in mice and rats, which may be related to the impairment of the skin homeostasis observed with aging. The decreased taurine content of the epidermis in aged animals was able to be rescued by taurine supplementation.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Anastasiya Börsch ◽  
Daniel J. Ham ◽  
Nitish Mittal ◽  
Lionel A. Tintignac ◽  
Eugenia Migliavacca ◽  
...  

AbstractSarcopenia, the age-related loss of skeletal muscle mass and function, affects 5–13% of individuals aged over 60 years. While rodents are widely-used model organisms, which aspects of sarcopenia are recapitulated in different animal models is unknown. Here we generated a time series of phenotypic measurements and RNA sequencing data in mouse gastrocnemius muscle and analyzed them alongside analogous data from rats and humans. We found that rodents recapitulate mitochondrial changes observed in human sarcopenia, while inflammatory responses are conserved at pathway but not gene level. Perturbations in the extracellular matrix are shared by rats, while mice recapitulate changes in RNA processing and autophagy. We inferred transcription regulators of early and late transcriptome changes, which could be targeted therapeutically. Our study demonstrates that phenotypic measurements, such as muscle mass, are better indicators of muscle health than chronological age and should be considered when analyzing aging-related molecular data.


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