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Cellular and molecular landscapes of human tendons across the lifespan revealed by spatial and single-cell transcriptomics
Tendon injuries are common and heal poorly, whereas developing tendons repair with minimal scarring; how this capacity declines with age remains poorly understood. Here, we combine histology, single-nucleus, single-cell, and spatial transcriptomic profiling of human Achilles and quadriceps tendons across embryonic, fetal, and adult stages, including ruptured adult tendons. We identify seven embryonic progenitor states that are predicted to contribute to three tendon-associated...
Mediterranean diet preserves renal mitochondrial homeostasis and attenuates early diabetic kidney injury in db/db mice
CONCLUSIONS: A balanced MD-based dietary mix preserves renal structure and function in db/db mice by counteracting oxidative stress, mitochondrial dysfunction, and early fibrotic remodeling. These findings support the MD as a potential nutritional strategy to enhance renal resilience and mitigate metabolic stress-induced kidney aging in the context of diabetes and obesity.
Socio-economic influences from egg to exit: Emerging biology
Socio-economic status (SES) impacts life-long health from early development to old age. We review SES differences in biological factors that begin before fertilization and extend into later life, 'egg to exit'. SES gradients are shown in onset and prevalence of chronic conditions including cardiovascular disease, diabetes and dementia, leading up to a 15-year difference in life expectancy in some countries. Our analysis is limited to high-income countries and does not include detailed discussion...
Metabolic flexibility following resistance exercise and a high protein diet in older men: results from a 12-week randomized controlled trial
CONCLUSION: In older men, RE improved metabolic flexibility. PRO had a limited benefit. No synergistic effects were observed.
Structural basis for prostaglandin and drug transport via SLCO2A1
Organic anion-transporting polypeptide transporters (SLCO/OATPs) function as cellular gatekeepers, regulating intestinal absorption, hepatic and renal clearance, and the tissue distribution of drugs and metabolites in the human body. However, the mechanisms underlying substrate selection within the SLCO superfamily remain unclear, hampering efforts to rationalize the interaction of drugs and metabolites with these transporters. SLCO2A1 (also known as OATP2A1) is responsible for the distribution...
Mitorubin, berberrubine-based compounds that improve mitochondrial function, exhibit cardioprotective effects against age-related cardiac dysfunction
Mitochondria play a central role in cellular energy metabolism and homeostasis, and their dysfunction is closely linked to the progression of age-related diseases. The mitochondrial ubiquitin ligase MITOL (also known as MARCHF5) is a key regulator of mitochondrial dynamics and function, and reduced MITOL expression in the mouse heart has been implicated in mitochondrial dysfunction and cardiac aging. In this study, we identified berberrubine as a compound that promotes MITOL expression and...
Modified letrozole vs GnRH antagonist protocols in ovarian aging women for IVF: an open-label, multicenter, randomized controlled trial
For women with diminished ovarian reserve or of advanced age, controlled ovarian stimulation presents a significant challenge during in vitro fertilization cycles. This multi-center, open-label, randomized controlled trial enrolled 318 women with diminished ovarian reserve (defined as an antral follicle count < 5 or anti-Müllerian hormone level of 0.1-1.1 ng/mL) or advanced age (40-45 years) between 2020 and 2023. Participants were assigned to either a modified letrozole protocol (mLP, n = 159)...
Briefing Chat: Are scientists funny? The evidence is in - and it's no joke
No abstract
Spontaneous aging-associated inflammation and genome instability in the immune system of turquoise killifish
Turquoise killifish (Nothobranchius furzeri) are naturally short-lived vertebrates that recapitulate key aspects of human aging. However, the molecular and cellular causes of systemic aging in killifish are poorly understood. Here we ask whether killifish undergo age-dependent changes in the main hematopoietic organ (kidney marrow), which may contribute to systemic aging. To characterize immune aging in killifish, we used single-cell RNA sequencing, cytometry and functional in vitro assays on...
A Service-Learning Program Based on Comprehensive Geriatric Assessment and Health Promotion in Older Adults: Protocol for the GEROS Project
No abstract
Microscopic spikes on snakeskin block bacterial buildup
Structures on python scales could inspire chemical-free antimicrobial designs
First science from private Moon lander challenges lunar divide
Blue Ghost data suggest NASA’s growing commercial Moon program can deliver results
Energy Department merges nuclear and particle physics programs, unsettling researchers
In spite of synergies, physicists worry both fields are being sidelined in favor of AI
Impact of P-glycoprotein substrates on transendothelial transport of amyloid-β peptide in an in vitro model
Alzheimer's disease (AD) is a pervasive neurodegenerative disorder and the leading cause of dementia, strongly associated with amyloid β-peptide (Aβ) accumulation in the cerebrum. In most cases, this aggregation is primarily due to inefficiencies in the degradation and clearance of Aβ, notably its transport across the blood-brain barrier (BBB) into the bloodstream. This study investigates the role of P-glycoprotein (P-gp), a key transporter in transporting Aβ across endothelial-cell monolayers,...
Subtyping based on hippocampal cryptic exon burden reveals proteome-wide changes associated with TDP-43 and Alzheimer's disease pathology
TDP-43 pathology defines limbic-predominant age-related TDP-43 encephalopathy (LATE-NC) and frequently co-occurs with Alzheimer's disease neuropathologic change (ADNC), yet the molecular consequences of overlapping pathology remain unclear. We performed biochemical and proteomic analyses of postmortem hippocampal tissue from 90 individuals spanning control, LATE-NC, ADNC, and ADNC+LATE-NC groups. Cryptic exon (CE) inclusion was quantified across eight TDP-43-regulated transcripts and related to...
What percentage of neuromuscular strength reduction in older adults determines the decline in walking speed?
CONCLUSION: Losing 15% or more of neuromuscular strength reduces walking speed over time. Therefore, monitoring the percentage change in NS can serve as a useful tool for early detection of the risk of WS decline, allowing for more personalised clinical investigations and timely neuromuscular strengthening interventions to minimise adverse effects on mobility in older adults.
IFN-β as a therapeutic agent for influenza A virus infection in old mice
CONCLUSIONS: IFN-β administration to IAV-infected old mice improved overall outcome without worsening lung damage and inhibited neuroinflammatory and brain damage-associated pathways. These results suggest IFN-β warrants further investigation as adjunctive treatment for severe viral infections in select hosts.
A parsimonious six-predictor model for memory decline: cross-population validation in Chinese and Japanese aging cohorts
To develop and validate a parsimonious risk model for short-term memory decline in older adults and to evaluate its cross-population transportability between Chinese and Japanese cohorts. The model was developed in 5985 cognitively normal older adults from the China Health and Retirement Longitudinal Study (CHARLS, 2011-2015). Seven machine learning algorithms were compared, and a Cox proportional hazards (CoxPH) model was selected for its optimal balance between performance and parsimony. The...
FGF21-Mediated Upregulation of SIRT1 Delays Intervertebral Disc Degeneration by Promoting PINK1/Parkin Dependent Mitophagy Through Deacetylation of FOXO3
Intervertebral Disc Degeneration (IDD) is a common degenerative spinal disease and a leading cause of low back pain and disability. The senescence of nucleus pulposus cells (NPCs) is a central mechanism driving the pathological progression of IDD, though its regulatory mechanisms remain unclear. Bioinformatic analysis identified FGF21 as a key gene regulating NPCs senescence. In both human and rat degenerated intervertebral discs, FGF21 expression was significantly downregulated and closely...
Age-Like Methylation Changes of HSCs in GADD45B Knockout Mice Define Methylation Sites Associated With Loss of Function
Hematopoietic stem cells (HSCs) self-renew and differentiate into all blood cells maintaining the hematopoietic system. Age-related HSC dysfunction impacts all of hematopoiesis, with DNA methylation alterations in aged HSCs contributing to altered function. Growth Arrest and DNA Damage-inducible proteins (Gadd45a, Gadd45b, and Gadd45g) are expressed in HSC activation, and Gadd45b has been reported to induce DNA demethylation. Thus, we explored the relationship between Gadd45b, DNA methylation...