Adult-onset depletion of sulfatide leads to axonal degeneration with relative myelin sparing.

3-O-sulfogalactosylceramide (sulfatide) constitutes a class of sphingolipids that comprise about 4% of myelin lipids in the central nervous system. Previously, our group characterized a mouse with sulfatide's synthesizing enzyme, cerebroside sulfotransferase (CST), constitutively disrupted. Using these mice, we demonstrated that sulfatide is required for establishment and maintenance of myelin, axoglial junctions, and axonal domains and that sulfatide depletion results in structural pathologies commonly observed in Multiple Sclerosis (MS).

Compromised Myelin and Axonal Molecular Organization Following Adult-Onset Sulfatide Depletion.

3-O-sulfogalactosylceramide, or sulfatide, is a prominent myelin glycosphingolipid reduced in the normal appearing white matter (NAWM) in Multiple Sclerosis (MS), indicating that sulfatide reduction precedes demyelination. Using a mouse model that is constitutively depleted of sulfatide, we previously demonstrated that sulfatide is essential during development for the establishment and maintenance of myelin and axonal integrity and for the stable tethering of certain myelin proteins in the sheath. Here, using an adult-onset depletion model of sulfatide, we employ a combination of ultrastructural, immunohistochemical and biochemical approaches to analyze the consequence of sulfatide depletion from the adult CNS.

Prepubertal castration eliminates sex differences in lifespan and growth trajectories in genetically heterogeneous mice.

Sex differences in aging and longevity have been widely observed, with females consistently outliving males across human populations. However, the mechanisms driving these disparities remain poorly understood. In this study, we explored the influence of post-pubertal testicular effects on sex differences in aging by prepubertally castrating genetically heterogeneous (UM-HET3) mice, a unique mouse model that emulates human sex differences in age-related mortality.

Fat talk, old talk, or both? Association of negative body talk with mental health, body dissatisfaction, and quality of life in men and women.

Background: Little research has investigated the harmful effects of old talk-negative age-related body talk-on mental health and quality of life despite substantial research examining fat talk. Old talk also has only been evaluated in women and in relation to few outcomes. Of note, old talk and fat talk are strongly correlated, suggesting possible overlap in elements that drive negative outcomes.

Health Characteristics and Aspirin Use in Participants at the Baseline of the ASPirin in Reducing Events in the Elderly - eXTension (ASPREE-XT) Observational Study.

Background: Aspirin as a primary preventative in healthy older adults did not prolong disability-free survival in the ASPREE randomized trial. Observational studies following randomized trials allow assessment of benefits and harms which may not appear during the trial. We describe health characteristics, physical function, and aspirin use in the ASPREE-eXTension (ASPREE-XT) observational study cohort.

Acute inflammation alters lung lymphocytes and potentiates innate-like behavior in young mouse lung CD8 T cells, resembling lung CD8 T cells from old mice.

Inflammation plays a significant role in lung infection including that caused by Mycobacterium tuberculosis, in which both adaptive and innate lymphocytes can affect infection control. How inflammation affects infection is understood in a broad sense, including inflammaging (chronic inflammation) seen in the elderly, but the explicit role that inflammation can play in regulation of lymphocyte function is not known. To fill this knowledge gap, we used an acute lipopolysaccharide (LPS) treatment in young mice and studied lymphocyte responses, focusing on CD8 T cell subsets.

Soluble pathogenic tau enters brain vascular endothelial cells and drives cellular senescence and brain microvascular dysfunction in a mouse model of tauopathy.

Vascular mechanisms of Alzheimer's disease (AD) may constitute a therapeutically addressable biological pathway underlying dementia. We previously demonstrated that soluble pathogenic forms of tau (tau oligomers) accumulate in brain microvasculature of AD and other tauopathies, including prominently in microvascular endothelial cells. Here we show that soluble pathogenic tau accumulates in brain microvascular endothelial cells of P301S(PS19) mice modeling tauopathy and drives AD-like brain microvascular deficits.

Eating disorder pathology in a sample of midlife and older adults experiencing food insecurity.

Researchers have recently identified food insecurity (FI) as a risk factor for eating disorder pathology (EDP). Yet, associations between FI and EDP remain understudied in midlife and older adults. The current study is a descriptive and exploratory re-analysis of Becker et al.

The association between frailty and incident cardiovascular disease events in community-dwelling healthy older adults.

Study Objective: This study examined the association between frailty and incident cardiovascular disease (CVD) events, major adverse cardiovascular events (MACE), and CVD-related mortality.

Design: Longitudinal cohort study.

Setting: The ASPirin in Reducing Events in the Elderly (ASPREE) clinical trial in Australia and the United States.

Acetyl-CoA carboxylase 1 is a suppressor of the adipocyte thermogenic program.

Disruption of adipocyte de novo lipogenesis (DNL) by deletion of fatty acid synthase (FASN) in mice induces browning in inguinal white adipose tissue (iWAT). However, adipocyte FASN knockout (KO) increases acetyl-coenzyme A (CoA) and malonyl-CoA in addition to depletion of palmitate. We explore which of these metabolite changes triggers adipose browning by generating eight adipose-selective KO mouse models with loss of ATP-citrate lyase (ACLY), acetyl-CoA carboxylase 1 (ACC1), ACC2, malonyl-CoA decarboxylase (MCD) or FASN, or dual KOs ACLY/FASN, ACC1/FASN, and ACC2/FASN.

Longitudinal association between handgrip strength, gait speed and risk of serious falls in a community-dwelling older population.

Objective: Both grip strength and gait speed can be used as markers of muscle function, however, no previous study has examined them in the same population with respect to risk of falls.

Methods: In this prospective cohort study, utilising data from the ASPirin in Reducing Events in the Elderly (ASPREE) trial and ASPREE-Fracture substudy, we analysed the association of grip strength and gait speed and serious falls in healthy older adults. Grip strength was measured using a handheld dynamometer and gait speed from 3-metre timed walks.

Targeting hepatic serine-arginine protein kinase 2 ameliorates alcohol-associated liver disease by alternative splicing control of lipogenesis.

Background And Aims: Lipid accumulation induced by alcohol consumption is not only an early pathophysiological response but also a prerequisite for the progression of alcohol-associated liver disease (ALD). Alternative splicing regulates gene expression and protein diversity; dysregulation of this process is implicated in human liver diseases. However, how the alternative splicing regulation of lipid metabolism contributes to the pathogenesis of ALD remains undefined.

Posttraumatic stress disorder and other mental health correlates in a predominantly Latino/Hispanic sample living with food insecurity.

Objective: Food insecurity (FI) is a global public health concern that is associated with psychopathology, including depression and anxiety. Individuals living with social disadvantages, such as experiencing low SES or being part of minoritized populations, are at higher risk of developing lifetime posttraumatic stress disorder (PTSD) following trauma exposure. Yet relatively little is known about PTSD prevalence rates and the potential mental health burden in populations with FI.

Prediabetes, diabetes and loss of disability-free survival in a community-based older cohort: a post-hoc analysis of the ASPirin in Reducing Events in the Elderly trial.

Background: Evidence for the prognostic implications of hyperglycaemia in older adults is inconsistent.

Objective: To evaluate disability-free survival (DFS) in older individuals by glycaemic status.

Methods: This analysis used data from a randomised trial recruiting 19,114 community-based participants aged ≥70 years, who had no prior cardiovascular events, dementia and physical disability.

HILPDA promotes NASH-driven HCC development by restraining intracellular fatty acid flux in hypoxia.

Background & Aims: The prevalence of non-alcoholic steatohepatitis (NASH)-driven hepatocellular carcinoma (HCC) is rising rapidly, yet its underlying mechanisms remain unclear. Herein, we aim to determine the role of hypoxia-inducible lipid droplet associated protein (HILPDA)/hypoxia-inducible gene 2 (HIG2), a selective inhibitor of intracellular lipolysis, in NASH-driven HCC.

Methods: The clinical significance of HILPDA was assessed in human NASH-driven HCC specimens by immunohistochemistry and transcriptomics analyses.

Rapamycin restores peripheral blood flow in aged mice and in mouse models of atherosclerosis and Alzheimer's disease.

Peripheral artery disease (PAD), defined as reduced blood flow to the lower limbs, is a serious disorder that can lead to loss of function in the lower extremities and even loss of limbs. One of the main risk factors for PAD is age, with up to 25% of adults over the age of 55 and up to 40% over the age of 80 presenting with some form of the disease. While age is the largest risk factor for PAD, other risk factors include atherosclerosis, smoking, hypertension, and diabetes.

Binge eating age of onset, frequency, and associated emotional distress among women aged 60 years and over.

Emerging research indicates that binge eating is prevalent among older adult women. This study explored the characteristics of older women (aged 60+ years) with objective binge episodes (OBE) in later-life, including age of onset, distress, and frequency of OBE. Data consist of telephone clinical interviews conducted with individuals presenting for participation in a biomedical study of older women with OBE to establish inclusion criteria.

Age-dependent loss of hepatic SIRT1 enhances NLRP3 inflammasome signaling and impairs capacity for liver fibrosis resolution.

Our studies indicate that the longevity factor SIRT1 is implicated in metabolic disease; however, whether and how hepatocyte-specific SIRT1 signaling is involved in liver fibrosis remains undefined. We characterized a functional link of age-mediated defects in SIRT1 to the NLRP3 inflammasome during age-related liver fibrosis. In multiple experimental murine models of liver fibrosis, we compared the development of liver fibrosis in young and old mice, as well as in liver-specific SIRT1 knockout (SIRT1 LKO) mice and wild-type (WT) mice.

Psychological health among older adult women in the United States during the COVID-19 pandemic.

This study examined differences in mental health in older adult women before versus during the COVID-19 pandemic. Participants who were community dwelling ( = 227) included  = 67 women aged 60-94 in the pre-pandemic group and  = 160 women aged 60-85 in the peri-pandemic group who completed self-report measures assessing mental health and quality of life (QOL). We compared mental health and QOL indices across the pre- and peri-pandemic groups.

DOPAL initiates αSynuclein-dependent impaired proteostasis and degeneration of neuronal projections in Parkinson's disease.

Dopamine dyshomeostasis has been acknowledged among the determinants of nigrostriatal neuron degeneration in Parkinson's disease (PD). Several studies in experimental models and postmortem PD patients underlined increasing levels of the dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL), which is highly reactive towards proteins. DOPAL has been shown to covalently modify the presynaptic protein αSynuclein (αSyn), whose misfolding and aggregation represent a major trait of PD pathology, triggering αSyn oligomerization in dopaminergic neurons.

De novo lipogenesis fuels adipocyte autophagosome and lysosome membrane dynamics.

Adipocytes robustly synthesize fatty acids (FA) from carbohydrate through the de novo lipogenesis (DNL) pathway, yet surprisingly DNL contributes little to their abundant triglyceride stored in lipid droplets. This conundrum raises the hypothesis that adipocyte DNL instead enables membrane expansions to occur in processes like autophagy, which requires an abundant supply of phospholipids. We report here that adipocyte Fasn deficiency in vitro and in vivo markedly impairs autophagy, evident by autophagosome accumulation and severely compromised degradation of the autophagic substrate p62.

Prevalence and socio-economic determinates of food insecurity in Veterans: findings from National Health and Nutrition Examination Survey.

Objective: To determine predictors of the association between being a Veteran and adult food security, as well as to examine the relation of potential covariates to this relationship.

Design: Data collected during 2011-2012, 2013-2014 and 2015-2016 National Health and Nutrition Examination Survey (NHANES) were pooled for analyses. Veterans (self-reported) were matched to non-Veterans on age, race/ethnicity, sex and education.

Biomimetic hematoma delivers an ultra-low dose of rhBMP-2 to successfully regenerate large femoral bone defects in rats.

Successful repair of large bone defects remains a clinical challenge. Following fractures, a bridging hematoma immediately forms as a crucial step that initiates bone healing. In larger bone defects the micro-architecture and biological properties of this hematoma are compromised, and spontaneous union cannot occur.