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Meningeal lymphatic vessels drain brain fluid and waste into the cervical lymph nodes, but how removing these nodes during surgery affects brain health is unknown. Retrospective analysis of cancer patients who underwent neck lymphadenectomy without chemo-radiation therapy found that up to 25% developed mild-to-severe cognitive impairment, and neuroimaging showed accelerated temporal horn enlargement after bilateral surgery. To determine mechanistically how cervical lymphadenectomy contributes to...

Circumventricular organs (CVOs) are small brain regions lacking a blood-brain barrier, giving neurons direct access to blood-borne signals, yet how these microenvironments shape the origin and phenotype of local macrophages remains unclear. Using multi-omics, we characterized the immune landscape of two CVOs, the area postrema (AP) and median eminence (ME), revealing brain-border-like environments with a unique macrophage compartment. CVO microglia showed a distinct, heterogeneous phenotype,...

AMP-activated protein kinase (AMPK) is a key evolutionarily conserved sensor of energy homeostasis and plays a central role in metabolic health and disease. AMPK has also been implicated in ageing; however, most in vivo drug studies rely on the use of indirect activators, such as metformin, which have complex modes-of-action, therefore making conclusions on the specific role of AMPK more challenging. Here, we demonstrate that direct activation of AMPK with the compound 991 extends lifespan in...

Cellular senescence and chronic low-grade inflammation occupy a central, mechanistically coupled position among the hallmarks of aging. Natural killer (NK) cells decline in per-cell cytotoxicity with age, and lower NK cell cytotoxicity has been associated with higher cancer incidence and infection-related mortality in older adults. NK cells are also endogenous effectors of senescent-cell clearance, engaging stress-induced NKG2D and DNAM-1 ligands and depending on perforin-mediated cytolysis....

Large-scale functional connectivity gradients provide a compact description of cortical organization, capturing hierarchical transitions from unimodal sensory systems to transmodal association cortex. Although these gradients have become a central framework for studying macroscale brain organization, it remains unclear whether they systematically map onto regional cortical biology. Here we show that functional gradient position robustly predicts cortical thickness and regional glucose...

Tauopathies, including Alzheimer's disease, are age-related neurodegenerative disorders characterized by abnormal phosphorylation and buildup of microtubule-associated protein tau. Gene expression dysregulation is a key molecular feature of tauopathies, but how aging and disease interact to disrupt crucial transcriptional regulators and pathways remains largely unknown. Here, we examined how pathological tau affects gene expression programs in age-related neurodegenerative disease using a...

CONCLUSION: The prevalence of pain is relatively high among older people in Mexico. Targeted intervention measures should be taken to improve awareness of the risk factors and the prevention of pain.

Age-related megakaryocyte (MK) dysfunction disrupts platelet production and may increase thrombotic risk, but whether coenzyme Q10 (CoQ10) restores MK homeostasis through autophagy remains unclear. Male C57BL/6J mice aged 1, 9, 15, 19, 21, or 23 months received CoQ10 for 12 weeks. Bone marrow MK proliferation, CD41/CD61 expression, DNA polyploidy, autophagy-associated proteins, and platelet phenotypes were evaluated. H(2)O(2)-induced senescent MEG-01 cells were used for pharmacological...

Age-related hearing loss (ARHL) is a prevalent sensory disorder in the elderly, yet the molecular mechanisms underlying cochlear aging remain incompletely understood. While insulin-like growth factor 1 (IGF-1) has been implicated in ARHL, its role in the stria vascularis, particularly in pericyte-mediated blood-labyrinth barrier (BLB) regulation, is poorly defined. We performed transcriptomic analysis of FACS-purified pericytes from young and aged mouse stria vascularis. Functional studies were...

Atherosclerosis, recognized as a prototypical age-associated vascular disease, is driven by macrophage foam cell formation. Individuals with Parkinson's disease (PD) exhibit an elevated risk for stroke. While α-synuclein (α-Syn) is known for its neuronal role in PD, its presence in the circulation and potential vascular effects remain unexplored. Here, we identify α-Syn as a previously unrecognized circulating factor that promotes atherosclerosis. α-Syn was detected in human atherosclerotic...

Senolytic CAR-T cells targeting uPAR induce dose-dependent toxicities. Although dosage adjustment mitigates these toxicities in laboratory mice, clinical translation remains challenging owing to the unpredictability of CAR-T cell proliferation across heterogeneous patient populations. In contrast, bispecific T-cell engagers (BiTEs) offer a safer alternative with superior dose-titratability. Here, we have developed a GFD-CD3 BiTE by employing the growth factor-like domain (GFD) of the natural...

Maintenance of lipid and redox homeostasis is essential for stress resistance and longevity, but the transcriptional networks coordinating these processes remain incompletely understood. In Caenorhabditis elegans, the transcription factors SKN-1A/Nrf1 and SKN-1C/Nrf2 mediate distinct stress responses that promote proteostasis, lipid homeostasis, and oxidative stress resistance. Here, we identify the Krüppel-like factor KLF-1 as a regulator of lipid accumulation that modulates SKN-1 activity....

Cognitive impairment (CI) associated with aging and immunosenescence is linked to metabolic alterations. Microglial senescence and dysregulated autophagy have been implicated as major contributors to this process, but the underlying metabolic regulators remain unclear. This study aimed to identify key metabolic regulators of CI and elucidate their underlying mechanisms. Human cohort analyses, older and D-galactose (D-gal)-induced mouse models, and microglial cell models were integrated to...