Aggregator

Bone marrow stromal cells, marked by leptin receptor (Lepr) and C-X-C motif chemokine ligand 12 (Cxcl12), orchestrate osteogenesis and maintain bone homeostasis. Following injury, these stromal cells directly generate reparative bone and subsequently restore the marrow microenvironment, a process widely regarded as a reliable regenerative response. However, it remains unclear whether stromal cells retain full regenerative capacity after prior injury. Here, we show that Lepr^(+)Cxcl12^(+) stromal...

No abstract

Alzheimer's disease (AD) remains one of the most challenging neurodegenerative disorders, primarily due to the lack of reliable tools for its early and non-invasive diagnosis. Exosomes, nanosized extracellular vesicles secreted by neural and peripheral cells, have emerged as promising biomarkers reflecting the molecular alterations associated with AD pathogenesis. Fourier Transform Infrared (FTIR) spectroscopy, with its capacity to capture unique biochemical fingerprints of biomolecules,...

No abstract

Our previous study identified CD4 cytotoxic T lymphocytes (CD4 CTLs) as a hallmark of supercentenarians. CD4 CTLs have primarily been studied in disease contexts; however, their role in healthy aging remains unclear. Using single-cell immune profiling, we analyzed T cells from supercentenarians and found that CD4 CTLs begin to expand around the age of 100, characterized by sequential CD27/CD28 loss without exhaustion. CD4 CTLs were dominated by large clones, with top clones averaging 33.3%,...

Air pollution is the leading environmental cause of disease burden worldwide and is increasingly recognized as a potent driver of accelerated biological aging. Rather than acting through organ-specific toxicity alone, air pollutants appear to affect the fundamental hallmarks of aging itself, including oxidative stress, chronic inflammation, epigenetic dysregulation, telomere attrition, mitochondrial dysfunction, and cellular senescence. The pollutants of greatest concern are fine and ultrafine...

Aging features two linked immune traits: immunosenescence and chronic low-grade inflammaging. Other than senescent lymphocytes, pathologically remodelled macrophages are key drivers of age-related immune dysfunction, mainly via tryptophan (Trp) metabolism through the kynurenine pathway (KP) and microbiota-related indole pathway. This review suggests a bidirectional amplification loop model, in which dysbiosis of the microbiota in the aged gut causes decreased production of microbial indoles and...

Tau protein aggregates adopt distinct conformations across tauopathies, yet the protein interactions engaged by disease-specific polymorphs remain poorly characterized. Here, we demonstrate that conformationally distinct tau polymorphs associate with disease-specific interaction networks across Alzheimer's disease (AD), progressive supranuclear palsy (PSP), and dementia with Lewy bodies (DLB). Interactome profiling of tau aggregates from PBS- and sarkosyl-soluble brain fractions identified 493...

Synucleinopathies, including idiopathic Parkinson's Disease, are driven by misfolding and aggregation of the 140 residue α-synuclein protein that plays a role in presynaptic vesicle regulation. We describe effects of a modifier, neuronal overexpression of the mouse calcium-activated potassium channel subunit Kcnn1, on a mouse model in which transgenic Thy1.2-driven human A53T α-synuclein directs fully penetrant lethal motor disease. Kcnn1 overexpression increased median survival of these mice...

Regulatory T (T(reg)) cells prevent autoimmune diseases but limit antitumor immunity. Tumor‑infiltrating Treg (Ti‑T(reg)) cells exhibit metabolic traits as potential antitumor targets. Here, we find that Ti-T(reg) cells upregulate glutamate dehydrogenase 1 (GDH1), increasing α-ketoglutarate (α-KG) levels. Elevated GDH1 in Ti-T(reg) cells accelerates tumor progression. Mechanistically, in a lactate rich microenvironment, GDH1 lactylation boosts α-KG production to fuel ALKBH5-mediated Wnt2...

No abstract

CONCLUSIONS: In our sample of studies evaluating CKD palliative care interventions, limited quality domains were addressed, a variety of measurement tools were used, and less than a quarter of studies were conducted only in older adults. Future research should address the holistic nature of palliative care, apply standardized instruments, and increase inclusion of older adults.

CONCLUSIONS: These findings highlight the adverse association of central adiposity and the limitations of BMI-only classification for mortality risk stratification in older adults.

CONCLUSIONS: Significant gaps exist in the integration of geriatric competencies across postgraduate medical training programs. Coordinated efforts are needed to integrate and assess these competencies to prepare physicians to care for aging populations.

CONCLUSION: These findings suggest that abdominal CT-derived liver attenuation and relative adiposity phenotypes may capture systemic tissue-level metabolic variations relevant to MRI-derived brain aging in women.

Alzheimer's disease (AD) has long been framed around amyloid-beta (Aβ) and tau pathology, yet mounting evidence indicates that dysfunctional microglia-astrocyte crosstalk is an important, and often underappreciated, contributor to disease progression that operates alongside-rather than in place of-neuronal, vascular, and proteinopathic mechanisms. Here we propose a three-stage framework in which glial communication transitions from silent vulnerability through organized defense to maladaptive...

CONCLUSIONS: Cardiorespiratory fitness seems to be a determinant of the resting metabolic rate in older adults, and lower 1-MET values would be expected in individuals with poorer vs. higher VO(2peak).

This perspective distinguishes two standards that are often used as if they were interchangeable. Optimal health is a standard built by medicine and expressed through guideline targets and biomarkers. Adequate health is the threshold of functioning that allows a person to live in a way they themselves experience as sufficient and dignified. Building on the concept of homeodynamic space as the biological substrate of adequate independence, on the older salutogenic tradition that asked what...

Understanding how osteoblasts build and remodel bone matrix in vivo remains a fundamental challenge because cellular metabolism and matrix turnover are difficult to resolve across time and space within mineralized tissues. Here, we developed an integrated imaging platform combining stable isotope labeling with correlative electron microscopy and nanoscale secondary ion mass spectrometry (NanoSIMS) to visualize bone cell metabolism and matrix dynamics at nanometer resolution in vivo. This...

The consequence of enhanced energy metabolism for health and life span of organisms is a fundamental yet controversially discussed issue of life and aging among others because of the fact that increasing energy metabolism often entails the risk of oxidative damage. To resolve this paradox, we introduce the bacterial-derived lipoic acid protein ligase A (LplA) as an orthogonal and defined molecular tool to enhance energy metabolism and at the same time to foster a low oxidative stress...