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Chaperone-mediated autophagy manipulates PGC1α stability and governs energy metabolism under thermal stress

3 weeks 5 days ago
Thermogenic proteins are down-regulated under thermal stress, including PGC1α· However, the molecular mechanisms are not fully understood. Here, we addressed that chaperone-mediated autophagy could regulate the stability of PGC1α under thermal stress. In mice, knockdown of Lamp2a, one of the two components of CMA, in BAT showed increased PGC1α protein and improved metabolic phenotypes. Combining the proteomics of brown adipose tissue (BAT), structure prediction, co-immunoprecipitation- mass...
Yixiao Zhuang

pS396/pS404 (PHF1) tau vaccine outperforms pS199/pS202 (AT8) in rTg4510 tauopathy model

3 weeks 5 days ago
Tauopathies, including Alzheimer's disease (AD) and Frontotemporal Dementia (FTD), are histopathologically defined by the aggregation of hyperphosphorylated pathological tau (pTau) as neurofibrillary tangles in the brain. Site-specific phosphorylation of tau occurs early in the disease process and correlates with progressive cognitive decline, thus serving as targetable pathological epitopes for immunotherapy development. Previously, we developed a vaccine (Qβ-pT181) displaying phosphorylated...
Jonathan P Hulse

Multiplex imaging of amyloid-β plaques dynamics in living brains with quinoline-malononitrile-based probes

3 weeks 5 days ago
The dynamic behaviour of amyloid-β (Aβ) plaques in Alzheimer's disease remains poorly understood, and accumulation and distribution of Aβ plaques must be inferred from in vitro pathological changes in brain tissue. In situ detection of Aβ plaques in live imaging is challenging because of the lack of adequate probes. Here we report the design of unimolecular quinoline-malononitrile-based Aβ probes, termed QMFluor integrative framework, that binds in vivo to Aβ plaques, making them detectable via...
Jianfeng Dai

Identifying New Risk Factors for Comorbidities in the Elderly

3 weeks 5 days ago
CONCLUSION: This study underscores the importance of HDL-C and FBG as critical biomarkers for assessing comorbidity risk in the elderly and reveals the potential application of the nomogram prediction model in the risk prediction and management of elderly comorbidities. These findings support using these indicators in predicting and intervening comorbidities in the elderly, providing substantial evidence for further research and clinical practice.
Yuge Jiang

The Impact of Living at Moderate Altitude in the United States: Epidemiology and Key Research Questions

3 weeks 5 days ago
Over the last twenty years, the United States (US) has seen a significant population migration into moderate elevation locations (defined as elevations 1,800- 2,500 meters (m) for the purposes of this review). While considerable research has investigated how chronic diseases are impacted on acute ascent to high altitude, little research has examined how residing at high altitude impacts longer term health including risk of various disease states and long-term morbidity, with even fewer studies...
Elan Small

A 20-Second Video-Based Assessment of Cognitive Frailty: Results from a Cohort Study within the Precision Aging Network

3 weeks 5 days ago
CONCLUSIONS: The 20-second vFM test offers a practical, non-invasive, easy-to-implement, and accessible solution for objectively evaluating cognitive frailty, demonstrating high predictive accuracy in distinguishing at-risk individuals. Its integration into telehealth platforms could enhance early detection and enable timely interventions, promoting healthier aging trajectories. Further longitudinal studies are recommended to validate its utility in tracking cognitive and physical decline over...
Bijan Najafi

Decoding Precision Aging: The Intersection of Cognitive Decline, Frailty, and Hormonal Biomarkers

3 weeks 5 days ago
CONCLUSIONS: This study highlights practical and efficient methods for assessing frailty emphasizing the value of dual-task testing and cortisol measures in identifying individuals at higher risk for cognitive and physical decline. The findings underscore the importance of integrating hormonal markers with cognitive and physical assessments to enhance risk stratification and intervention planning in aging populations.
J Ray Runyon

Reference centiles for intrinsic capacity to monitor clinical health outcomes in real-world primary care cohorts

3 weeks 5 days ago
Intrinsic capacity (IC) refers to physical and mental capacities that determine healthy aging. IC is the central element of the World Health Organization care pathway 'Integrated Care for Older People' (ICOPE). However, the operationalization of a composite IC measurement in clinical settings remains to be defined. We used screening data from ICOPE implementation in a real-life population of 27,706 adults 60 years or older that were users of primary care services to elaborate and cross-validate...
Philipe de Souto Barreto

Safety and tolerability of intravenous liposomal GM1 in patients with Parkinson disease: A single-center open-label clinical phase I trial (NEON trial)

3 weeks 5 days ago
CONCLUSION: TLN is safe and well-tolerated in general. This prospective phase I trial revealed non-allergic habituating acute infusion reactions at the second, third, or fourth treatment that can be prevented by a slower rate of infusion. Importantly, the exploratory results suggest a consistent improvement of signs and symptoms of PD.
Stefan Halbherr

CaMK modulates sensory neural activity to control longevity and proteostasis

3 weeks 5 days ago
The impact of neural activity on aging and longevity remains poorly understood, with limited understanding of the specific neuron groups and molecular mechanisms that regulate lifespan. In this study, we uncover a correlation between human longevity and reduced CaMK4 expression in the frontal cortex. We further show that this link is conserved in Caenorhabditis elegans, where the loss of the homolog CMK-1 leads to increased longevity and enhanced proteostasis. These beneficial effects are...
Ranran Zhao

DLK/JNK3 Upregulation Aggravates Hair Cell Senescence in Mice Cochleae via Excessive Autophagy

3 weeks 5 days ago
Cell death mediated by the abnormal activation of autophagy has been observed in many neurodegenerative diseases. Dual leucine zipper kinase (DLK), a member of the mitogen-activated protein kinase cascade, plays a key role in regulating cellular autophagy and the progression of neurodegenerative diseases. However, its role in age-related hearing loss has not been reported. In this study, we found that DLK, phosphorylated c-Jun N-terminal kinase (p-JNK), and JNK3 expression increased in the...
Rui Ding

A cross-sectional study of how high-frequency hearing loss impacts cognitive functions in middle-aged-to-older adults

3 weeks 5 days ago
CONCLUSION: While both speech and higher-frequency hearing loss were associated with poorer cognition, only the former demonstrated effects beyond those of ageing. However, the present study only investigated two frequencies in the higher range, encouraging broader investigation of higher-frequency hearing's cognitive effects in the future.
Dona M P Jayakody