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In vivo metabolic tagging and targeting of circulating red blood cells

11 hours 54 minutes ago
Engineering red blood cells (RBCs) has been widely explored for drug delivery, imaging, vaccination, and other applications. However, effective strategies to directly engineer RBCs in vivo are still lacking. Here, we report successful metabolic glycan labeling of RBCs in vivo. We demonstrate that systemically administered azido-sugars can metabolically label circulating RBCs with azido groups, through labeling of both mature RBCs and RBC precursor cells. The surface azido tags on RBCs can...
Yusheng Liu

Cannabinoids and cognition in Parkinson's disease: Insights from animal models and emerging clinical evidence

1 day 11 hours ago
Parkinson's disease (PD) is a progressive, multisystem neurodegenerative disorder characterized not only by motor impairments but also by a broad spectrum of debilitating non-motor symptoms, including cognitive decline. The cognitive function depends on neuronal plasticity, which is tightly regulated by multiple signaling systems, among which the endocannabinoid system (ECS) plays a significant role. Over the past three decades, substantial evidence has accumulated regarding how endogenous...
Valentina F Kitchigina

The p75NTR Signaling Axis: Bridging Neurodevelopmental Homeostasis, Pathological Mechanisms, and Therapeutic Strategies in Neurodegenerative Diseases

1 day 11 hours ago
The neurotrophin receptor p75 (p75NTR) plays dual, context-dependent roles in the nervous system that are regulated by ligand binding, co-receptor interactions, and microenvironmental cues. During neurodevelopment, synaptic plasticity, and in neurodegenerative disorders, p75NTR orchestrates opposing cellular responses: it can support neuronal homeostasis through pro-survival pathways, while also initiating apoptotic and inflammatory cascades that exacerbate disease progression. In Alzheimer's...
Jiawei Wu

Modeling and evaluating longitudinal brain maintenance and cognitive reserve using episodic memory, brain structure, and functional connectivity in older adults

1 day 11 hours ago
Cognitive reserve (CR) and brain maintenance (BM) reflect better than expected cognition despite brain pathology and minimal age-related brain changes that explain stable cognition, respectively. Despite being commonly used, joint quantification of these concepts has been limited; our aim is to derive longitudinal CR and BM measures and investigate CR's relationship with education and functional connectivity. We analyzed longitudinal data from 451 participants (241 female, age(mean) = 68.5...
Rachel M Morse

Biological evidence of the life expectancy limit in human aging

1 day 11 hours ago
Life expectancy (LE) at birth has increased in many countries throughout the twentieth and twenty-first centuries. Future LE values are estimated by extrapolating existing data. However, it remains difficult to determine the LE limit using mathematical models such as the Kannisto model and the Gompertz function due to significant random fluctuations in centenarian mortality rates. There are 12 biological hallmarks of ageing, including epigenetic changes and senescent cells. These microscopic...
Yasuhiro Kitazoe

Unlocking the role of microbiome through gut-skin axis to alleviate aging: current perspectives and future scope

1 day 11 hours ago
The microbiota of intestinal origin has a significant impact on the aging process, affecting skin health and overall cell longevity. Aging is marked by physiological alterations, such as enhanced oxidative stress, which is intensified by external factors like UV radiation and environmental pollution. The gut microbiota profoundly influences immune functions and results in reduced inflammation, which contributes to the anti-aging process. The present review is an attempt to showcase the current...
Arun Kumar Mishra

Aging disrupts sympathetic innervation of the thymus

1 day 11 hours ago
The thymus, a primary lymphoid organ essential for lifelong T cell development, undergoes progressive age-related involution. The thymus is innervated by the sympathetic nervous system (SNS), but the extent of innervation and its relationship to the microenvironment or age-related involution remain unclear. Here, we provide a detailed mapping of thymic sympathetic innervation using advanced imaging methods to characterize its distribution and relationship with vascular structures, capsule, and...
Randall S Carpenter

Cellular and molecular landscapes of human tendons across the lifespan revealed by spatial and single-cell transcriptomics

1 day 11 hours ago
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...
Alina Kurjan

Mediterranean diet preserves renal mitochondrial homeostasis and attenuates early diabetic kidney injury in db/db mice

1 day 11 hours ago
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.
Giovanna Mercurio

Socio-economic influences from egg to exit: emerging biology

1 day 11 hours ago
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...
Marja Jylhä

Structural basis for prostaglandin and drug transport via SLCO2A1

1 day 11 hours ago
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...
Chitra Joshi

Mitorubin, berberrubine-based compounds that improve mitochondrial function, exhibit cardioprotective effects against age-related cardiac dysfunction

1 day 11 hours ago
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...
Michio Sato

Modified letrozole vs GnRH antagonist protocols in ovarian aging women for IVF: an open-label, multicenter, randomized controlled trial

1 day 11 hours ago
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)...
Yang Zhao

Spontaneous aging-associated inflammation and genome instability in the immune system of turquoise killifish

1 day 11 hours ago
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...
Gabriele Morabito