Aging & Longevity

Neurodegenerative diseases, such as amyotrophic lateral sclerosis, are often associated with mutations in stress granule proteins. Aberrant stress granule condensate formation is associated with disease, making it a potential target for pharmacological intervention. Here, we identified lipoamide, a small molecule that specifically prevents cytoplasmic condensation of stress granule proteins. Thermal proteome profiling showed that lipoamide stabilizes intrinsically disordered domain-containing...

Aging negatively impacts central nervous system function; however, there is limited information about the cellular impact of aging on peripheral nervous system function. Importantly, injury to vulnerable peripheral axons of dorsal root ganglion (DRG) neurons results in somatosensory dysfunction, such as pain, at higher rates in aged individuals. Cellular senescence is common to both aging and injury and contributes to the aged pro-inflammatory environment. We discovered DRG neuron senescence in...

CONCLUSION: The integration of the MPI into multidisciplinary taking care of old patients with hip fractures may provide a structured approach for individualizing treatment decisions, considering aspects such as prognosis, functional autonomy, and cognitive status. Further studies are needed to validate the long-term outcomes of this approach.

As the Pacific Plate migrates over the mantle plume below Hawai'i, magma flux decreases, resulting in changes in eruptive volume, style, and composition. It is thought that melt storage becomes deeper and ephemeral with the transition from highly voluminous tholeiitic (shield stage) to the less voluminous alkaline (post-shield and rejuvenation stages) magmatism. To quantitatively test this, we applied high-precision fluid inclusion barometry via Raman spectroscopy to samples from representative...

CONCLUSIONS: Loss of drug subsidies after Medicaid disenrollment was associated with higher mortality among low-income Medicare beneficiaries. (Funded by the National Institute on Aging and others.).

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New immunosenescence targets for preventing senescence-associated pathological cardiac hypertrophy (SA-PCH) need to be explored. In the present study, with physiologically aged human and mouse samples, the IL-17A level increased with physiological aging, heart failure (HF), and SA-PCH and was negatively correlated with thymic Bmi-1 expression. Bmi-1^(f/f)LckCre^(+) mice and Bmi-1^(f/f) littermates were generated to determine whether Bmi-1 delayed T cell aging by maintaining thymic T cell...

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.

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...

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...

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.

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...

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...

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...

CONCLUSION: These findings demonstrate the presence of obvious fractal physical activity complexity in aged adults with cSVD.

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.

The research focused on exploring the differences and relationships between gut microbiota and metabolites at various stages of Alzheimer's disease (AD), specifically using APP/PS1 mice at the ages of 6 months and 10 months. To assess metabolites in serum and cortex, and to evaluate gut microbiota profiles in cecal content, UPLC-MS/MS and 16S rRNA sequencing techniques were utilized, respectively. Findings indicated that, in comparison to younger mice, serum concentrations of L-Leucine, thymine,...

Brown adipose tissue (BAT) plays a vital role in non-shivering thermogenesis and energy metabolism and is influenced by factors like environmental temperature, ageing, and obesity. However, the molecular mechanisms behind BAT development and thermogenesis are not fully understood. Our study identifies the m⁶A reader protein YTHDC1 as a crucial regulator of postnatal interscapular BAT development and energy metabolism in mice. YTHDC1 directly interacts with PPARγ through its intrinsically...

Endothelial cell senescence is a key driver of cardiovascular aging, yet little is known about the mechanisms by which it is induced in vivo. Here we show that the gut bacterial metabolite phenylacetic acid (PAA) and its byproduct, phenylacetylglutamine (PAGln), are elevated in aged humans and mice. Metagenomic analyses reveal an age-related increase in PAA-producing microbial pathways, positively linked to the bacterium Clostridium sp. ASF356 (Clos). We demonstrate that colonization of young...

Sex differences in Parkinson's disease (PD) offer insights into mechanisms of dopaminergic cell resilience. Female dopamine (DA) neurons are more resilient via mechanisms that remain unclear. Here, we discovered key sex and regional differences in mitochondrial generation of cytotoxic reactive oxygen species (ROS) and their implications for DA neuron resilience using the Drosophila model. While aging raised mitochondrial ROS in DA neurons of both sexes, we observed a sexually dimorphic response...