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Taking antibiotics? Sugar may be making the damage worse
Eating more sugar while taking antibiotics was linked to greater disruption of the gut microbiome and increased growth of potentially harmful bacteria. Researchers say temporarily cutting back on sweets during and after antibiotic treatment could be a simple way to reduce this damage, though clinical trials are still needed.
World’s once-largest penguin colony is in perilous decline
Climate change appears to have made food scarce for chinstrap penguins, which had numbered more than 1 million on a remote South Atlantic island
Drug target could block brain inflammation linked to Alzheimer’s and Parkinson’s
Blocking a receptor called P2X7 significantly reduced inflammation in human brain tissue, revealing a potential new treatment strategy for neurological and psychiatric disorders. The discovery could help researchers repurpose existing drugs for conditions including traumatic brain injury, Alzheimer’s, Parkinson’s, depression, and schizophrenia.
Was this odd animal the world’s first milk suckler?
Ancient swimming creature provides clues to when nursing evolved
Human microglia clear intraneuronal α-synuclein aggregates by GPNMB-mediated trogocytosis
Microglia are the primary immune cells of the brain, but their role in Parkinson's disease is not fully understood. Chronic microglial activation is toxic to neurons, but in the early stages of pathology, microglia also exert beneficial functions. We used induced pluripotent stem cell (iPSC)-derived coculture models to investigate how human microglia respond to α-synuclein aggregates that form de novo inside human dopaminergic neurons with α-synuclein gene triplication or are triggered by...
Age-Associated Gut Microbiota Dysbiosis Impairs Antiviral Defense During Influenza Virus Infection and Identifies Acetate as a Protective Mediator in Senescent Human Lung Cells
Aging is associated with profound alterations in gut microbiota composition and function, including reduced production of short-chain fatty acids (SCFAs), yet it remains unclear whether these age-related microbial changes directly contribute to impaired antiviral defense during influenza A virus (IAV) infection. To address this question, we first characterized age-associated alterations of the gut microbiome and SCFA-related metabolic potential in a murine model of IAV infection. We then used a...
Chronic Senolytic Treatment and/or Aerobic Exercise Reduce Senescence and Improve Myocardial Function During Aging in the Heart
Aging is the predominant risk factor for cardiac dysfunction, driven primarily through a decline in cardiomyocyte and overall myocardial performance. Cellular senescence is becoming increasingly linked to its development, as senescent cardiomyocytes and interstitial cells accumulate with age and exhibit persistent DNA damage, mitochondrial dysfunction, and inflammation that collectively impair ventricular relaxation and contractility. Senolytics, which selectively eliminate senescent cells,...
Inhibiting Glutaminase Reverses Senescence-Associated Mitochondrial Dysfunction and Skeletal Muscle Decline
Age-associated loss of skeletal muscle mass and function, also known as sarcopenia, is closely linked to mitochondrial dysfunction. In this study, we report that senescent skeletal muscle myoblasts exhibit elevated activity and expression of the enzyme glutaminase (GLS1), which is mediated by p38 MAPK signaling and leads to intracellular urea accumulation that impairs mitochondrial function. Pharmacological inhibition of GLS1 with CB-839 reduced urea levels, restored the expression of electron...
Association between community toilet deprivation and depression among older adults in India: a multilevel analysis of the Longitudinal Aging Study in India from 2017-2018
Community context is an important determinant of health for older and aging adults. However, much of the research examining these associations has focused on Western contexts. Features and attributes of communities in low- and middle-income countries that might also shape health outcomes among older adults are less understood. This cross-sectional study examines community-level toilet coverage in India as a possible determinant of depression among adults over 45. We applied a multilevel modeling...
Dietary preference, biological aging, and incident dementia: a prospective cohort study
Dietary patterns are modifiable determinants of dementia risk, but the interactions between individual dietary preference profiles, biological aging, and dementia risk remain unclear. We aimed to investigate associations of dietary preference profiles with biological aging and incident dementia, as well as the potential modifying effect of genetic susceptibility. Dietary preference profiles were identified using latent profile analysis on food preferences questionnaire data. Cox models estimated...
An integrated resource for systems-level analysis of aging hallmarks and associated genes
AgingHallmarksDB is an interactive web platform designed to facilitate systems-level aging research centered on 11 aging hallmarks. It comprises 3111 aging hallmark-associated genes integrated from seven established databases, including a high-confidence consensus set comprising 1089 genes. It further incorporates tissue, cell-type class, exosomes, protein-protein and regulatory interactions to facilitate deeper biological insights. AgingHallmarksDB enables over representation analysis (ORA) and...
Socioeconomic Differences in the Association Between the Big Five Personality Traits and Episodic Memory Trajectories in Midlife and Old Age
CONCLUSION: Our findings underscore the relevance of wealth as an important socioeconomic resource for cognitive health beyond income and education, particularly in old age, when income is typically reduced. Overall, the results support modest concurrent associations between personality, SES, and episodic memory levels, but provide hardly any evidence for longitudinal effects. More frequent and longer-term longitudinal assessments are needed to clarify potential effects on cognitive aging.
Epigenetic insights into extreme longevity in the world's oldest terrestrial animal, Jonathan
Aldabra giant tortoises (Aldabrachelys gigantea) are exceptionally long-lived. We sequenced the genome and methylome of Jonathan, a 194-year-old Aldabra, to explore the molecular basis of his longevity. Relative to other giant tortoises (A. gigantea and Chelonoidis abingdonii), Jonathan has unique gene variants in most aging pathways. Moreover, Jonathan has substantial DNA methylation and methylation entropy changes compared to four other Aldabras ranging in age from a 5-year-old juvenile to...
Endogenous retrovirus control of calbindin is essential for human early embryogenesis
The cis-regulatory potential of human endogenous retroviruses (HERVs) that have accumulated in our genome affects diverse host processes, including embryonic development and malignancy, where HERV epigenetic control is reduced. Non-small cell lung cancer optimal growth requires cancer cell-intrinsic expression of the calcium-binding protein calbindin under the control of a HERVH integrant on chromosome 8q21.3. Chimeric transcription of HERVH and CALB1, encoding calbindin, is also observed in...
Human trilayer engineered blood vessel reveals influence of fibroblasts on disease progression in model of Hutchinson-Gilford progeria
In vitro models of vascular disease have focused primarily on the pathophysiology of smooth muscle cell (SMC) or endothelial cell (EC). Adventitial fibroblasts can contribute to disease progression, but their specific influence is not well understood in different disease contexts. To elucidate fibroblast's impact on vascular pathology, we developed trilayer tissue-engineered blood vessels (TEBVs) with SMCs, ECs, and fibroblasts. We modeled atherosclerosis in the accelerated aging disease,...
Association between atherogenic dyslipidemia and DBS-derived p-tau217 in older adults: evidence from SHARE DBS data
CONCLUSION: In this cross-sectional analysis, higher AIP, reflecting atherogenic dyslipidemia, was associated with a modestly higher DBS-derived p-tau217 concentration in older adults. The biological and clinical significance of this association remains to be established in longitudinal and multimodal studies.
Average performance and performance variability on a brief functional fine motor test reflect distinct behavioral constructs in aging
Prior work in older adults has developed a brief functional fine motor test, which involves repeated timed trials of an upper-limb task. Performance has been associated with global and domain-specific neuropsychological tests as well as putative markers of Alzheimer's disease when scored using variability in trial time; however, the extent to which task performance depends on motor ability has not been established nor quantified. This retrospective study examined whether mean trial time and...
A computational-first proof-of-concept for dual-function metal chelation and aggregate neutralization in an Aβ42 <em>Drosophila</em> model
Alzheimer's disease (AD) pathology is amplified by a self-reinforcing metal-Aβ-ROS axis, in which redox-active Cu and Fe bound to Aβ N-terminal histidines catalyze Fenton-like ROS generation and accelerate aggregation. Existing single-target interventions - anti-amyloid antibodies, antioxidants, metal-protein attenuating compounds, aggregation inhibitors, and photooxygenation catalysts - each address only one node of this loop. We used a computational-first framework to evaluate a dual-function...
Deep cervical lymphovenous reconstruction in Alzheimer's disease: three target-defined interfaces with distinct mechanistic implications
Age-related impairment of brain solute clearance has been implicated in Alzheimer's disease (AD), yet procedures described as deep cervical lymphovenous reconstruction do not necessarily target the same lymphatic structure. This review examines glymphatic exchange, meningeal lymphatic drainage, cervical outflow, human lymphatic imaging, lymphatic surgery, early clinical studies, registered trials, and reported harms. Three interfaces can be distinguished: lymphatic flap-vein, lymph node-vein,...
Scientists reprogram immune cells inside the body to fight cancer
Scientists at UC San Francisco have developed a way to create cancer-fighting CAR-T cells directly inside the body, potentially avoiding the slow and extremely expensive process of removing, engineering, and reinfusing a patient’s immune cells. Using a two-particle delivery system, the researchers sent CRISPR gene-editing tools and new cancer-targeting DNA specifically into T cells, where the DNA was inserted at a precise location in the genome.