Adolescent expectations of early death predict young adult socioeconomic status

Among adolescents, expectations of early death have been linked to future risk behaviors. These expectations may also reduce personal investment in education and training, thereby lowering adult socioeconomic status attainment. The importance of socioeconomic status is highlighted by pervasive health inequities and dramatic differences in life expectancy among education and income groups. The objectives of this study were to investigate patterns of change in perceived chances of living to age 35 (Perceived Survival Expectations; PSE), predictors of PSE, and associations between PSE and future socioeconomic status attainment. We utilized the U.S. National Longitudinal Study of Adolescent Health (Add Health) initiated in 1994-95 among 20,745 adolescents in grades 7-12 with follow-up interviews in 1996 (Wave II), 2001-02 (Wave III) and 2008 (Wave IV; ages 24-32). At Wave I, 14% reported ≤ 50% chance of living to age 35 and older adolescents reported lower PSE than younger adolescents. At Wave III, PSE were similar across age. Changes in PSE from Wave I to III were moderate, with 89% of respondents reporting no change (56%), one level higher (22%) or one level lower (10%) in a 5-level PSE variable. Higher block group poverty rate, perceptions that the neighborhood is unsafe, and less time in the U.S. (among the foreign-born) were related to low PSE at Waves I and III. Low PSE at Waves I and III predicted lower education attainment and personal earnings at Wave IV in multinomial logistic regression models controlling for confounding factors such as previous family socioeconomic status, individual demographic characteristics, and depressive symptoms. Anticipation of an early death is prevalent among adolescents and predictive of lower future socioeconomic status. Low PSE reported early in life may be a marker for worse health trajectories

Diammonium Glycyrrhizinate Upregulates PGC-1α and Protects against Aβ1–42-Induced Neurotoxicity

Mitochondrial dysfunction is a hallmark of beta-amyloid (Aβ)-induced neurotoxicity in Alzheimer's disease (AD), and is considered an early event in AD pathology. Diammonium glycyrrhizinate (DG), the salt form of Glycyrrhizin, is known for its anti-inflammatory effects, resistance to biologic oxidation and membranous protection. In the present study, the neuroprotective effects of DG on Aβ1–42-induced toxicity and its potential mechanisms in primary cortical neurons were investigated. Exposure of neurons to 2 µM Aβ1–42 resulted in significant viability loss and cell apoptosis. Accumulation of reactive oxygen species (ROS), decreased mitochondrial membrane potential, and activation of caspase-9 and caspase-3 were also observed after Aβ1–42 exposure. All these effects induced by Aβ1–42 were markedly reversed by DG treatment. In addition, DG could alleviate lipid peroxidation and partially restore the mitochondrial function in Aβ1–42-induced AD mice. DG also significantly increased the PGC-1α expression in vivo and in vitro, while knocking down PGC-1α partially blocked the protective effects, which indicated that PGC-1α contributed to the neuroprotective effects of DG. Furthermore, DG significantly decreased the escape latency and search distance and increased the target crossing times of Aβ1–42-induced AD mice in the Morris water maze test. Therefore, these results demonstrated that DG could attenuate Aβ1–42-induced neuronal injury by preventing mitochondrial dysfunction and oxidative stress and improved cognitive impairment in Aβ1–42-induced AD mice, indicating that DG exerted potential beneficial effects on AD

NHR-49 Helps Germline-Less Worms Chew the Fat

In C. elegans, removal of the germline extends lifespan significantly. We demonstrate that the nuclear hormone receptor, NHR-49, enables the response to this physiological change by increasing the expression of genes involved in mitochondrial β-oxidation and fatty-acid desaturation. The coordinated augmentation of these processes is critical for germline-less animals to maintain their lipid stores and to sustain de novo fat synthesis during adulthood. Following germline ablation, NHR-49 is up-regulated in somatic cells by the conserved longevity determinants DAF-16/FOXO and TCER-1/TCERG1. Accordingly, NHR-49 overexpression in fertile animals extends their lifespan modestly. In fertile adults, nhr-49 expression is DAF-16/FOXO and TCER-1/TCERG1 independent although its depletion causes age-related lipid abnormalities. Our data provide molecular insights into how reproductive stimuli are integrated into global metabolic changes to alter the lifespan of the animal. They suggest that NHR-49 may facilitate the adaptation to loss of reproductive potential through synchronized enhancement of fatty-acid oxidation and desaturation, thus breaking down some fats ordained for reproduction and orchestrating a lipid profile conducive for somatic maintenance and longevity

X Chromosome Crossover Formation and Genome Stability in Caenorhabditis elegans Are Independently Regulated by xnd-1

The germ line efficiently combats numerous genotoxic insults to ensure the high fidelity propagation of unaltered genomic information across generations. Yet, germ cells in most metazoans also intentionally create double-strand breaks (DSBs) to promote DNA exchange between parental chromosomes, a process known as crossing over. Homologous recombination is employed in the repair of both genotoxic lesions and programmed DSBs, and many of the core DNA repair proteins function in both processes. In addition, DNA repair efficiency and crossover (CO) distribution are both influenced by local and global differences in chromatin structure, yet the interplay between chromatin structure, genome integrity, and meiotic fidelity is still poorly understood. We have used the xnd-1 mutant of Caenorhabditis elegans to explore the relationship between genome integrity and crossover formation. Known for its role in ensuring X chromosome CO formation and germ line development, we show that xnd-1 also regulates genome stability. xnd-1 mutants exhibited a mortal germ line, high embryonic lethality, high incidence of males, and sensitivity to ionizing radiation. We discovered that a hypomorphic allele of mys-1 suppressed these genome instability phenotypes of xnd-1, but did not suppress the CO defects, suggesting it serves as a separation-of-function allele. mys-1 encodes a histone acetyltransferase, whose homolog Tip60 acetylates H2AK5, a histone mark associated with transcriptional activation that is increased in xnd-1 mutant germ lines, raising the possibility that thresholds of H2AK5ac may differentially influence distinct germ line repair events. We also show that xnd-1 regulated him-5 transcriptionally, independently of mys-1, and that ectopic expression of him-5 suppressed the CO defects of xnd-1. Our work provides xnd-1 as a model in which to study the link between chromatin factors, gene expression, and genome stability

Adolescent expectations of early death predict young adult socioeconomic status

Among adolescents, expectations of early death have been linked to future risk behaviors. These expectations may also reduce personal investment in education and training, thereby lowering adult socioeconomic status attainment. The importance of socioeconomic status is highlighted by pervasive health inequities and dramatic differences in life expectancy among education and income groups. The objectives of this study were to investigate patterns of change in perceived chances of living to age 35 (Perceived Survival Expectations; PSE), predictors of PSE, and associations between PSE and future socioeconomic status attainment. We utilized the U.S. National Longitudinal Study of Adolescent Health (Add Health) initiated in 1994-95 among 20,745 adolescents in grades 7-12 with follow-up interviews in 1996 (Wave II), 2001-02 (Wave III) and 2008 (Wave IV; ages 24-32). At Wave I, 14% reported ≤ 50% chance of living to age 35 and older adolescents reported lower PSE than younger adolescents. At Wave III, PSE were similar across age. Changes in PSE from Wave I to III were moderate, with 89% of respondents reporting no change (56%), one level higher (22%) or one level lower (10%) in a 5-level PSE variable. Higher block group poverty rate, perceptions that the neighborhood is unsafe, and less time in the U.S. (among the foreign-born) were related to low PSE at Waves I and III. Low PSE at Waves I and III predicted lower education attainment and personal earnings at Wave IV in multinomial logistic regression models controlling for confounding factors such as previous family socioeconomic status, individual demographic characteristics, and depressive symptoms. Anticipation of an early death is prevalent among adolescents and predictive of lower future socioeconomic status. Low PSE reported early in life may be a marker for worse health trajectories