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Real-time in vivo monitoring of levodopa pharmacokinetics is essential to address its narrow therapeutic window in Parkinson's disease (PD) therapy. However, current methods require excessive sample volumes, suffer low sampling frequencies, and fail to capture complete pharmacokinetic profiles. Here, we present an in vivo monitoring system for real-time tracking of levodopa levels in interstitial fluid (ISF) using a spindle-shaped carbon nanotube (CNT) fiber electrochemical sensor functionalized...

Hundreds of human kinases, including PINK1-a protein kinase associated with familial Parkinson's disease-are regulated by Hsp90 and its cochaperones. While previous studies have elucidated the mechanism of kinase loading into the Hsp90 machinery, the subsequent regulation of kinases by Hsp90 and its cochaperones remains poorly understood. In this study, using complexes obtained through PINK1 pulldown, we determine the cryo-EM structures of the human Hsp90-Cdc37-PINK1 complex at 2.84 Å,...

Liraglutide, a glucagon-like peptide 1 (GLP-1) agonist and antidiabetic drug, has shown neuroprotective effects in animal models. In this study, we aimed to evaluate the safety and efficacy of liraglutide in mild to moderate Alzheimer's disease syndrome. 'Evaluating liraglutide in Alzheimer's disease' (ELAD) is a multicenter, randomized, double-blind, placebo-controlled phase 2b trial in 204 participants with mild to moderate Alzheimer's disease syndrome with no diabetes. Participants received...

Among the marine bioresources, sea urchins are emerging as a promising provider of bioactive compounds with broad therapeutic potentials, including for ageing and age-related diseases. This review highlights the therapeutic promise of sea urchin bioactive compounds, covering evidence from both laboratory and clinical studies. Compounds found in sea urchin such as carotenoids, polyhydroxynaphthoquinones (PHNQs), and flavonoids demonstrate antioxidant and anti-inflammatory properties with notable...

Eukaryotic cells rely on mitochondria to fine-tune their metabolism in response to environmental and nutritional changes. However, how mitochondria adapt to nutrient availability and how diets impact mitochondrial disease progression, remain unclear. Here, we show that lipid-derived diets influence the survival of Caenorhabditis elegans carrying a hypomorphic wah-1/AIFM1 mutation that compromises mitochondrial Complex I assembly. Comparative proteomic and lipidomic analyses reveal that the...

Oxidized phosphatidylcholines (OxPCs) are neurotoxic byproducts of oxidative stress elevated in the central nervous system (CNS) during progressive multiple sclerosis (P-MS). How OxPCs contribute to the pathophysiology of P-MS is unclear. Here we show that stereotactic OxPC deposition in the CNS of mice induces a chronic compartmentalized lesion with pathological features similar to chronic active lesions found in P-MS. Using this model, we found that although microglia protected the CNS from...

CONCLUSION: These preliminary findings suggest potential benefits of the dance intervention for physical and psychosocial well-being among older adults, warranting further evaluation in larger, adequately powered randomized studies. Future research can investigate the pathways of how intergenerational dance intervention may enhance older adults' cognitive, physical, and psychosocial function over a longer term, as well as the relationships among these variables. Hence, more comprehensive and...

CONCLUSION: Our findings highlight unhappiness as the key factor in the sarcopenia risk network among older adults with diabetes. The key factors vary across different age and diabetes duration, highlighting the necessity of tailoring intervention strategies to individual patients. Objective support demonstrates a broad impact on sarcopenia risk across this population.

CONCLUSIONS: Different dimensions of smoking show robust and dose-response relationships with composite biomarkers-based BA acceleration. Our findings confirm that there is no safe level of smoking and emphasize the public health significance of achieving small but population-wide shifts in biological age by strengthening tobacco control measures.

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CONCLUSIONS: Multidomain geriatric indicators including anthropometric status (body mass index), walking aid use, cognitive function, age, and exhaustion can guide pragmatic, community-based screening for possible sarcopenia. Simple, accessible assessments of these predictors may facilitate earlier identification and referral, and should be considered in sarcopenia screening and prevention strategies.

CONCLUSIONS: Individuals with BHL did not show increased visual or somatosensory reliance and overall as a group showed similar balance performance to adults with normal hearing. Greater severity of hearing loss was associated with worse performance regardless of age. This study supports the role of regular exercise as protective against balance dysfunction in aging with or without hearing loss.

Life-history trade-offs between reproduction and survival are well documented, yet the biological mechanisms underlying costs remain unclear. Telomere length (TL) is a potential biomarker for such costs, although its association with reproductive efforts is mixed. Bats, particularly the long-lived greater horseshoe bat (Rhinolophus ferrumequinum), provide a rare opportunity to explore these dynamics due to their longevity and low reproductive rates. We examined telomere dynamics in 202 female R....

Specific class of immune cells help keep virus at bay for months or years—even in the absence of drugs

Age-related neurodegenerative diseases involve reduced cell numbers and impaired behavioral capacity. Neurodegeneration and behavioral deficits also occur during aging, and notably in the absence of disease. The cerebellum, which modulates movement and cognition, is susceptible to cell loss in both aging and disease. Here, we demonstrate that cerebellar Purkinje cell loss in aged mice is not spatially random but rather occurs in a pattern of parasagittal stripes. We also find that aged mice...

The proprioceptive and visual systems play a major role in daily tasks by providing continuous feedback to the central nervous system (CNS) for coordinating movements. However, it remains unclear to what extent alterations in the proprioceptive system and CNS affect vibration-induced illusion of movement (VIM) with age and after a stroke. To address this, 29 young (26 ± 7 years), 30 older (63 ± 8 years), and 26 stroke participants (68 ± 12 years) with left arm impairment, all right-handed,...

Caloric (CR) or dietary (DR) restriction improves health and extends lifespan in multiple species. However, the beneficial effects of DR may diminish if introduced late in life, emphasizing the importance of timing for promoting healthspan and avoiding adverse outcomes. Using a metabolomics approach, we investigated the metabolic responses in plasma, liver, and kidney of mice on acute and chronic DR at various ages. Two hundred and five mice including young (2-month-old; n = 72), middle-aged...