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Transcriptional memory of dFOXO activity in early adulthood delays late life mortality.

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE183542 | GEO | 2022/10/06

REPOSITORIES: GEO

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Transcriptional memory of dFOXO activity in early adulthood delays late life mortality [RNA-seq]

Project description:The study examined transcriptional memory after dFOXO induction in fat body and gut of young adult female fruit flies.

2022-10-06 | GSE183541 | GEO

Transcriptional memory of dFOXO activity in early adulthood delays late life mortality [ATAC-seq]

Project description:The study examined transcriptional memory after dFOXO induction in fat body and gut of young adult female fruit flies.

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Transcriptional memory of dFOXO activity in early adulthood delays late life mortality.

Project description:Transcriptional memory of dFOXO activity in early adulthood delays late life mortality.

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Transcriptional memory of dFOXO activity in early adulthood delays late life mortality [RNA-seq]

Project description:Transcriptional memory of dFOXO activity in early adulthood delays late life mortality [RNA-seq]

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Transcriptional memory of dFOXO activity in early adulthood delays late life mortality [ATAC-seq]

Project description:Transcriptional memory of dFOXO activity in early adulthood delays late life mortality [ATAC-seq]

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Transcriptional memory of dFOXO activation in youth curtails later-life mortality

Project description:Identifying processes occurring in early life affect subsequent life and health span is an urgent aim to improve human health. In this study, we identified a novel mechanism of dFOXO in longevity determination in Drosophila. We found that early adulthood induction of dFOXO is sufficient to reduce mortality in old age through different pathways than chronic dFOXO. We showed that dFOXO requires specific ATP-dependent chromatin modifiers to extend lifespan, and we could mimic this lifespan extension by modulating dFOXO’s targets in later life. Furthermore, dFOXO in early life induces a specific transcriptional programme that counteracts the natural transcriptomic changes occurring with age. Our findings provide a better understanding of transcriptional mechanisms related to longevity and opens new avenues for possible time-restricted interventions to improve human health in the future.

2022-09-28 | MTBLS3251 | MetaboLights

Transcriptional memory of dFOXO activation in youth curtails later-life mortality through chromatin remodeling and Xbp1.

Project description:A transient, homeostatic transcriptional response can result in transcriptional memory, programming subsequent transcriptional outputs. Transcriptional memory has great but unappreciated potential to alter animal aging as animals encounter a multitude of diverse stimuli throughout their lifespan. Here we show that activating an evolutionarily conserved, longevity-promoting transcription factor, dFOXO, solely in early adulthood of female fruit flies is sufficient to improve their subsequent health and survival in midlife and late life. This youth-restricted dFOXO activation causes persistent changes to chromatin landscape in the fat body and requires chromatin remodelers such as the SWI/SNF and ISWI complexes to program health and longevity. Chromatin remodeling is accompanied by a long-lasting transcriptional program that is distinct from that observed during acute dFOXO activation and includes induction of Xbp1. We show that this later-life induction of Xbp1 is sufficient to curtail later-life mortality. Our study demonstrates that transcriptional memory can profoundly alter how animals age.

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The Impact of Early Life Stress on Anxiety Symptoms in Late Adulthood.

Project description:Early life stress (ELS) may increase the risk of anxiety throughout the life course. Whether this effect extends to late adulthood is poorly known. In our study comprising 1872 participants from the Helsinki Birth Cohort Study born in 1934-1944, we investigated the association of various forms of ELS and their accumulation with self-reported anxiety symptoms at the age of 65-77 years. Data on childhood socioeconomic status and separation from parents were based on national registers for all participants. Information on self-reported emotional and physical trauma, parental divorce, and death of a family member in childhood was obtained from 1277 participants. We found that experiencing emotional trauma, physical trauma, and low socioeconomic status in childhood were associated with increased anxiety symptoms in late adulthood [B = 0.44 (95% CI = 0.31-0.58); B = 0.33 (95% CI = 0.20-0.46); B = 0.10 (95% CI = 0.01-0.19), respectively]. These associations remained significant even after controlling for other forms of ELS. Accumulation of early life stress also increased the levels of late-adulthood anxiety symptoms and the risk of anxiety regarded as clinically significant. Screening for potentially stressful childhood experiences in elderly populations may help identifying individuals with increased anxiety symptoms and planning preventive and therapeutic interventions for those exposed to ELS.

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Association of Early Adulthood Hypertension and Blood Pressure Change With Late-Life Neuroimaging Biomarkers.

Project description: Not available

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Early life physical activity and risk of ovarian cancer in adulthood.

Project description:Emerging data suggest that exposures in early life may affect ovarian development and contribute to ovarian cancer risk. We evaluated the association between early life physical activity and risk of ovarian cancer in adulthood in two large prospective cohorts, the Nurses' Health Study (NHS) and NHSII. In total, analyses included 28 232 NHS participants (followed from 2004 to 2016) and 56 553 NHSII participants (followed from 1997 to 2017). Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of ovarian cancer overall and by early life body mass index (BMI). Neither physical activity at ages 12-13, 14-17 or 18-22 years nor average physical activity across these three periods was associated with ovarian cancer risk overall (≥78 vs <24 MET-h/wk, HRs = 1.34, 1.21, 1.08 and 1.24, respectively), or by categories of early life BMI (Pheterogeneity ≥ .44). No association was observed with the risk of high-grade serous or poorly differentiated tumors or postmenopausal ovarian cancer. Overall, early life physical activity was not clearly related to ovarian cancer risk during adulthood.

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