Early life changes in histone landscape protect against age-associated amyloid toxicities through HSF-1-dependent regulation of lipid metabolism.

Transient events during development can exert long-lasting effects on organismal lifespan. Here we demonstrate that exposure of Caenorhabditis elegans to reactive oxygen species during development protects against amyloid-induced proteotoxicity later in life. We show that this protection is initiated by the inactivation of the redox-sensitive H3K4me3-depositing COMPASS complex and conferred by a substantial increase in the heat-shock-independent activity of heat shock factor 1 (HSF-1), a longevity factor known to act predominantly during C. elegans development. We show that depletion of HSF-1 leads to marked rearrangements of the organismal lipid landscape and a significant decrease in mitochondrial ß-oxidation and that both lipid and metabolic changes contribute to the protective effects of HSF-1 against amyloid toxicity. Together, these findings link developmental changes in the histone landscape, HSF-1 activity and lipid metabolism to protection against age-associated amyloid toxicities later in life.

Associations between Brief Resilience Scale scores and ageing-related domains in the Lothian Birth Cohort 1936.

[Correction Notice: An Erratum for this article was reported online in Psychology and Aging on Mar 5 2020 (see record 2020-16850-001). This article should have been published under the terms of the Creative Commons Attribution License (CC BY 3.0). Therefore, the article was amended to list the authors as copyright holders, and information about the terms of the CC BY 3.0 was added to the author note. In addition, the article is now open access. All versions of this article have been corrected.] It is unclear how scores on self-report resilience scales relate to key ageing-related domains in older age and if they truly measure resilience. We examined antecedents and outcomes of age-76 Brief Resilience Scale (BRS) scores in participants of the Lothian Birth Cohort 1936 (n = 655). We found bivariate associations between age-76 BRS scores and ageing-relevant antecedent variables measured at least 3 years earlier, from domains of cognitive ability, physical fitness, and wellbeing and, additionally, sociodemographics and personality (absolute r's from .082 to .49). Biological health variables were not associated with BRS scores. Age-73 cognitive ability (largest ß = 0.14), physical fitness (largest ß = 0.084), and wellbeing variables (largest ß = 0.26) made positive independent contributions to age-76 BRS scores in multivariate models. In a conservative model including all variables as covariates, corrected for multiple comparisons, only emotional stability (neuroticism) significantly independently contributed to BRS score (ß = 0.33). An exploratory backward elimination model indicated more wellbeing and personality associates of BRS scores (ßs from .087 to .32). We used latent difference score modeling to assess outcomes of BRS scores; we examined associations between age-76 BRS and change in latent factors of age-related domains between age 76 and 79. Whereas BRS scores were related cross-sectionally to levels of latent cognitive ability (r = .19), physical fitness (r = .20), and wellbeing (r = .60) factors, they were not related to declines in these domains. The independence of the BRS construct from established wellbeing and personality factors is unclear. (PsycInfo Database Record (c) 2020 APA, all rights reserved).