A list of this decade's most prominent names in ageing research would undoubtedly include many women who have led the field in recent years. While the field, and science in general, still have far to go in achieving gender parity in opportunities and recognition, we can celebrate the progress made to date. However, the longer 'history of the field' that many of us present in our classrooms, conference halls and writings often tends to be dominated by men.
View Article and Find Full Text PDFObjectives: To determine the frequency and clinical consequences of discrepancies in skeletal radiograph interpretation between emergency and radiology doctors in an Australian ED.
Methods: We reviewed the records of adult and paediatric patients assessed with skeletal radiography in an ED in Victoria, Australia over 3 months (January to March 2022). Epidemiological data, the interpretation of the radiograph by ED and radiology doctors, and clinical management of the patient were recorded to determine interpretation discrepancies and the consequences of these.
Although a lack of diversity in genetic studies is an acknowledged obstacle for personalized medicine and precision public health, Latin American populations remain particularly understudied despite their heterogeneity and mixed ancestry. This gap extends to COVID-19 despite its variability in susceptibility and clinical course, where ethnic background appears to influence disease severity, with non-Europeans facing higher hospitalization rates. In addition, access to high-quality samples and data is a critical issue for personalized and precision medicine, and it has become clear that the solution lies in biobanks.
View Article and Find Full Text PDFClin Sci (Lond)
November 2024
It has been recognized for over a century that feeding animals less food than they would normally eat increases lifespan and leads to broad-spectrum improvements in age-related health. A significant number of studies have subsequently shown that restricting total protein, branched chain amino acids or individual amino acids in the diet, as well as ketogenic diets, can elicit similar effects. In addition, it is becoming clear that fasting protocols, such as time-restricted-feeding or every-other-day feeding, without changes in overall energy intake can also profoundly affect rodent longevity and late-life health.
View Article and Find Full Text PDFtRNAs are evolutionarily ancient molecular decoders essential for protein translation. In eukaryotes, tRNAs and other short, noncoding RNAs are transcribed by RNA polymerase (Pol) III, an enzyme that promotes ageing in yeast, worms, and flies. Here, we show that a partial reduction in Pol III activity specifically disrupts tRNA levels.
View Article and Find Full Text PDFOrganismal growth and lifespan are inextricably linked. Target of Rapamycin (TOR) signalling regulates protein production for growth and development, but if reduced, extends lifespan across species. Reduction in the enzyme RNA polymerase III, which transcribes tRNAs and 5S rRNA, also extends longevity.
View Article and Find Full Text PDFBackground: Randomised controlled trials (RCTs) aim to estimate the causal effect of one or more interventions relative to a control. One type of outcome that can be of interest in an RCT is an ordinal outcome, which is useful to answer clinical questions regarding complex and evolving patient states. The target parameter of interest for an ordinal outcome depends on the research question and the assumptions the analyst is willing to make.
View Article and Find Full Text PDFPurpose: The aim was to assess the diagnostic yield of next generation sequencing (NGS) multi-gene panels for breast and ovarian cancer in a high-complexity cancer centre in Chile. Additionally, our goal was to broaden the genotypic spectrum of BRCA variants already identified in Chilean families.
Methods: Retrospective analysis was conducted on the genetic test results of 722 individuals from Fundación Arturo López Pérez's genetic counselling unit between 2016 and 2021.
The parasitic worm-derived immunomodulator, ES-62 rescues defective levels of IL-10-producing regulatory B cells (Bregs) and suppresses chronic Th1/Th17-driven inflammation to protect against joint destruction in the mouse collagen-induced arthritis (CIA) model of rheumatoid arthritis. Such autoimmune arthritis is also associated with dysbiosis of the gut microbiota and disruption of intestinal barrier integrity. We recently further exploited the CIA model to show that ES-62's prevention of joint destruction is associated with protection of intestinal barrier integrity and normalization of the gut microbiota, thereby suppressing the gut pathology that precedes the onset of autoimmunity and joint damage in CIA-mice.
View Article and Find Full Text PDFThe genetic pathways that modulate ageing in multicellular organisms are typically highly conserved across wide evolutionary distances. Recently RNA polymerase III (Pol III) was shown to promote ageing in yeast, C. elegans and D.
View Article and Find Full Text PDFPlasma cell leukemia (PCL) is a clinically aggressive variant of multiple myeloma, characterized by a high burden of circulating plasma cells, necessitating swift and accurate diagnosis due to its poor prognosis. The conventional diagnostic criteria, including the recent recommendation by the International Myeloma Working Group (IMWG) of > 5% circulating plasma cells as positive, have evolved over time. In this context, we present a detailed case report that underscores the pivotal role of the ADVIA 2120 automated hematology counter in detecting plasma cells through cytogram analysis, along with the significance of routine peripheral blood smear analysis and the utility of a large unstained cells (LUCs) threshold of > 4.
View Article and Find Full Text PDFMice develop pathology in the lungs as they age and this may be accelerated by a high calorie diet (HCD). ES-62 is a protein secreted by the parasitic worm that is immunomodulatory by virtue of covalently attached phosphorylcholine (PC) moieties. In this study, we show that weekly treatment of C57BL/6J mice with ES-62 protected against pathology in the lungs in male but not female mice fed a HCD from 10 weeks of age as shown by reductions in cellular infiltration and airway remodelling, particularly up to 160 days of age.
View Article and Find Full Text PDFBackground: Chronic kidney disease (CKD) is an age-related disease that displays multiple features of accelerated ageing. It is currently unclear whether the two treatment options for end-stage kidney disease (dialysis and kidney transplantation [KT]) ameliorate the accelerated uremic ageing process.
Methods: Data on clinical variables and blood DNA methylation (DNAm) from CKD stage G3-G5 patients were used to estimate biological age based on blood biomarkers (phenotypic age [PA], n = 333), skin autofluorescence (SAF age, n = 199) and DNAm (Horvath, Hannum and PhenoAge clocks, n = 47).
Extracellular vesicles (EVs), comprising microvesicles (MVs) and exosomes (Exos), are membranous vesicles secreted by cells which mediate the repair of cellular and tissue damage via paracrine mechanisms. The action of EVs under normative and morbid conditions in the context of ageing remains largely unexplored. We demonstrate that MVs, but not Exos, from Pathfinder cells (PCs), a putative stem cell regulatory cell type, enhance the repair of human dermal fibroblast (HDF) and mesenchymal stem cell (MSC) co-cultures, following both mechanical and genotoxic stress.
View Article and Find Full Text PDFHutchinson-Gilford progeria syndrome (HGPS) is a rare human disease characterised by accelerated biological ageing. Current treatments are limited, and most patients die before 15 years of age. Hydrogen sulfide (HS) is an important gaseous signalling molecule that it central to multiple cellular homeostasis mechanisms.
View Article and Find Full Text PDFDetection of respiratory viruses requires testing of the upper respiratory tract to obtain specimens for analysis. However, nasal and throat swabs can cause discomfort and procedural anxiety in children. Respiratory sampling methods which are accurate and less invasive are needed.
View Article and Find Full Text PDFIntroduction: Randomised controlled trials (RCTs) aim to assess the effect of one (or more) unproven health interventions relative to other reference interventions. RCTs sometimes use an ordinal outcome, which is an endpoint that comprises of multiple, monotonically ordered categories that are not necessarily separated by a quantifiable distance. Ordinal outcomes are appealing in clinical settings as specific disease states can represent meaningful categories that may be of clinical importance to researchers.
View Article and Find Full Text PDFObjectives: To compare health-related quality of life (HRQoL) at 25 and 18 years in individuals born extremely preterm (EP, <28 weeks' gestation) or with extremely low birth weight (ELBW, birth weight <1000 g) with term-born (≥37 weeks) controls. Within the EP/ELBW cohort, to determine whether HRQoL differed between those with lower and higher IQs.
Methods: HRQoL was self-reported using the Health Utilities Index Mark 3 (HUI3) at 18 and 25 years by 297 EP/ELBW and 251 controls born in 1991-1992 in Victoria, Australia.
Mitochondrial dysfunction is considered a highly conserved hallmark of ageing. However, most of the studies in both model and non-model organisms are cross-sectional in design; therefore, little is known, at the individual level, on how mitochondrial function changes with age, its link to early developmental conditions or its relationship with survival. Here we manipulated the postnatal growth in zebra finches (Taeniopygia guttata) via dietary modification that induced accelerated growth without changing adult body size.
View Article and Find Full Text PDFAim: Respiratory testing with rapid antigen tests (RATs) in children under 5 years of age may be uncomfortable and presents specific challenges to testing due to compliance and procedural distress. The aim of this study was to investigate sensitivity and feasibility of self-collected nasal and saliva RAT tests compared with a combined nose and throat (CTN) swab PCR in children under 5.
Methods: Children aged between 1 month and 5 years, with confirmed COVID-19 or who were a household contact within 7 days were included.
Despite significant increases in human lifespan over the last century, adoption of high calorie diets (HCD) has driven global increases in type-2 diabetes, obesity and cardiovascular disease, disorders precluding corresponding improvements in healthspan. Reflecting that such conditions are associated with chronic systemic inflammation, evidence is emerging that infection with parasitic helminths might protect against obesity-accelerated ageing, by virtue of their evolution of survival-promoting anti-inflammatory molecules. Indeed, ES-62, an anti-inflammatory secreted product of the filarial nematode , improves the healthspan of both male and female C57BL/6J mice undergoing obesity-accelerated ageing and also extends median lifespan in male animals, by positively impacting on inflammatory, adipose metabolic and gut microbiome parameters of ageing.
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