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Voxel-based morphometry (VBM) and surface-based morphometry (SBM) based on magnetic resonance structural imaging were used to identify disease progression in mild cognitive impairment (MCI) patients. A retrospective analysis was conducted on 154 MCI patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, with 62 patients classified into the progressive MCI (pMCI) group and 92 patients into the stable MCI (sMCI) group. VBM and SBM were employed to identify structural...

Autophagy is a pro-survival process that regulates the degradation and renewal of cellular components, making it a crucial mechanism for cellular homeostasis. There are selective forms of autophagy that are specific to a number of substrates, such as pathogens (bacteria or viruses), protein aggregates or excess/damaged organelles. These processes involve as key players autophagy receptors, that link the cargo to be degraded to the autophagic machinery. Among them, NDP52 (also known as CALCOCO2)...

Aging is characterized by a steady loss of physiological integrity, leading to impaired function and increased vulnerability to death. Cell senescence is a biological process that progresses with aging and is believed to be a key driver of age-related diseases. Senescence, a hallmark of aging, also demonstrates its beneficial physiological aspects as an anti-cancer, pro-regenerative, homeostatic, and developmental mechanism. A transitory response in which the senescent cells are quickly formed...

Several bat species live >20-40 years, suggesting that they possess efficient anti-aging and anti-cancer defenses. Here we investigate the requirements for malignant transformation in primary fibroblasts from four bat species Myotis lucifugus, Eptesicus fuscus, Eonycteris spelaea, and Artibeus jamaicensis - spanning the bat evolutionary tree and including the longest-lived genera. We show that bat fibroblasts do not undergo replicative senescence, express active telomerase, and show attenuated...

Therapy-induced senescence (TIS) is a major challenge in cancer therapy as senescent cancer cells provoke local and systemic inflammation and might be the cause of recurrences. Elucidation of pathways leading to TIS is of utmost importance for establishing strategies to counteract this. Previously we have shown that temozolomide (TMZ), an alkylating drug used forefront in glioma therapy, causes majorly cellular senescence, which is triggered by the primary damage O⁶-methylguanine, activating the...

Age-related changes in sleep have been associated with cognitive decline, yet causal pathways have not been identified. Evidence suggests reduced cardiovascular health may be a consequence of poor sleep and a precursor to cognitive decline. This observational cohort study used path analyses to determine whether cardiovascular disease risk mediated or moderated effects of sleep on yearly longitudinal change in cognition, estimated with linear growth models. Total sleep time (TST), sleep...

CONCLUSIONS AND IMPLICATIONS: Mexican American older adults with multimorbidity and high HGS had a 30% decreased risk of falls over time. Increasing muscle strength through exercise may help prevent falls among those with multimorbidity.

Most genetic conditions are described in pediatric populations, leaving a gap in understanding their clinical progression and management in adulthood. Motivated by other applications of large language models (LLMs), we evaluated whether Llama-2-70b-chat (70b) and GPT-3.5 (GPT) could generate plausible medical vignettes, patient-geneticist dialogues and management plans for a hypothetical child and adult patients across 282 genetic conditions (selected by prevalence and categorized based on...

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CONCLUSIONS: Molecular defects associated with the His139Arg, Tyr113His and P187S polymorphisms manifest as an observable change in the external appearance of the skin. This study underscores the need to move toward scrutinizing the ageing skin changes at molecular levels.

Alpha-synuclein (αSyn) is an intrinsically disordered protein that accumulates in the brains of patients with Parkinson's disease (PD). Through a high-throughput screen, we recently identified 38 genes whose knockdown modulates αSyn propagation. Here, we show that, among those, TAX1BP1 regulates how αSyn interacts with lipids, and ADAMTS19 modulates how αSyn phase separates into inclusions, adding to the growing body of evidence implicating those processes in PD. Through RNA sequencing, we...

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The incidence of age-associated ailments has increased proportionately with the expansion of the aging demographic. This study aimed to evaluate the anti-aging potential of synbiotic pineapple beverage formulated with 100% pineapple juice, 1% inulin, and Lacticaseibacillus rhamnosus ATCC 53103 (10 log CFU) in Caenorhabditis elegans and D-galactose age-induced mice. The synbiotic juice-treated nematodes exhibited a 24.52% increase in their lifespan, accompanied by lower levels of reactive oxygen...

Systematic reviews offer clarity about the effectiveness of interventions based on the best available evidence. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement updated previous guidance to ensure transparency in the reporting of systematic reviews of intervention effectiveness. To adhere to the 27 items of PRISMA 2020, aging-focused researchers must specify the choice of age-based criteria for the review, comprehensively identify studies, select the...

mtDNA mutator mice (Polg^(mut/mut) mice) have reinforced the mitochondrial theory of aging. These mice accumulate multiple mutations in mtDNA with age due to a homozygous proofreading-deficient mutation in mtDNA polymerase gamma (Polg), resulting in mitochondrial respiratory dysfunction and premature aging phenotypes. However, whether the accumulation of multiple mutations in Polg^(mut/mut) mice induces mitochondrial respiratory dysfunction remains unclear. Here, we determined the accurate mtDNA...

Advocates of animal research fear decision will lead to harassment of scientists and others who oversee such studies

A cocktail of antibodies from snake enthusiast Tim Friede protected mice from many deadly venoms—but some say the study has ethical issues

The ability to transplant immunologically foreign cells into an animal without immune suppression would be transformative. Pavan et al. show that human pluripotent stem cell-derived dopaminergic neuron progenitors engineered to express eight immune-evasive proteins can engraft in humanized mice and a rat model of Parkinson's disease without recourse to immune suppression.¹.

Transplantation of human fetal ventral mesencephalic tissue in individuals with Parkinson's disease has yielded clinical benefits but also side effects, such as graft-induced dyskinesias. The open-label TransEuro trial ( NCT01898390 ) was designed to determine whether this approach could be further developed into a clinically useful treatment. Owing to poor availability of human fetal ventral mesencephalic tissue, only 11 individuals were grafted at two centers using the same tissue preparation...

Recent advances have shown that single-nucleus RNA sequencing (snRNA-seq) can be applied to formalin-fixed, paraffin-embedded (FFPE) tissues, opening avenues for transcriptomic analysis of archived specimens. Yet, isolating intact nuclei remains difficult due to RNA cross-linking. Here, we introduce a cryogenic enzymatic dissociation (CED) strategy for rapid, high-yield and fidelity nuclei extraction from FFPE samples and validate its utility with snRandom-seq (snCED-seq) using male C57/BL6...