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Aging increases the risk of neurodegeneration, cognitive decline, and Alzheimer's disease (AD). We report that plasma concentrations of ubiquitin C-terminal hydrolase-L1 (UCH-L1) and neurofilament light (NfL) become exponentially higher from ages 2 to 85 in cross-sectional samples, serving as neuronal death/damage biomarkers across the lifespan. UCH-L1 concentrations rise faster in females, who exhibit increased AD risk. Glial fibrillary acidic protein (GFAP) concentrations increase...

Neuroimaging studies have highlighted both hyperconnectivity and hypoconnectivity across the Alzheimer's disease (AD) continuum, alongside task-induced activity changes. These alterations may reflect compensatory mechanisms or network breakdowns. While connectivity-based measures are not yet established as clinical biomarkers, they hold promises for evaluating therapeutic efficacy and informing the design of targeted interventions. Leveraging these insights, this review explores the potential of...

Alzheimer's disease (AD) is the most chronic neurodegenerative disease. The pathological hallmark of AD includes the accumulation of amyloid-beta plaques (Aβ), oxidative stress as well as chronic inflammatory reactions. Current treatments, such as acetylcholinesterase inhibitors, N-methyl-D-aspartate (NMDA) receptor antagonists, and recently approved monoclonal antibodies, offer symptomatic relief or slightly slow down progression. However, they too are constrained by high cost, side effects and...

Hydrogen sulfide is a gasotransmitter with biological functions, including roles in antioxidant defenses, mitochondrial bioenergetics, and cellular signaling via cysteine persulfidation. Several longevity-promoting interventions enhance endogenous hydrogen sulfide generation. However, whether enhanced hydrogen sulfide generation extends healthspan and lifespan in mammals remains unknown. Here, we investigated the in vivo effects of the non-enzymatic hydrogen sulfide generation promoted by...

Aging increases the risk of neurodegeneration, cognitive decline, and Alzheimer's disease (AD). We report that plasma concentrations of ubiquitin C-terminal hydrolase-L1 (UCH-L1) and neurofilament light (NfL) become exponentially higher from ages 2 to 85 in cross-sectional samples, serving as neuronal death/damage biomarkers across the lifespan. UCH-L1 concentrations rise faster in females, who exhibit increased AD risk. Glial fibrillary acidic protein (GFAP) concentrations increase...

CONCLUSIONS AND IMPLICATIONS: A long sleep duration (≥9 hours) is a risk factor for a decline in walking speed among men aged 60 years and older. Routine assessment of sleep duration in primary care provides a low-cost, scalable strategy to identify older adults at risk and guide early interventions aimed at maintaining mobility and independence, especially among older men.

CONCLUSIONS: In later life, being frail does not necessarily imply low IC, and vice versa. Frailty and low IC identify different groups in early older age, but the overlap between them becomes more pronounced with increasing age. Comprehensive assessment of ageing therefore requires measures that capture both vulnerability to decline and capacity.

Lithium-ion battery (LIB) recycling is crucial for energy security, environmental sustainability, and economic viability, as the finite lifespan of LIBs results in a significant annual accumulation of spent units. However, effectively and precisely recovering valuable metal ions such as Li^(+), Mn^(2+), Ni^(2+) and Co^(2+) from complex LIB leaching solutions remains a major challenge. Here, we present a scalable electro-membrane crystallization-assisted general recycling (e-MCGR) technology for...

White adipose tissue (WAT) is the primary energy storage organ and can be categorized mainly into subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). Although all WAT accumulates triglycerides to store excess energy, VAT is associated with pathological conditions, whereas SAT is considered beneficial for metabolic health. In fact, SAT and VAT are from distinct developmental origins. Moreover, within these depots, there is heterogeneity in developmental origin and in adipose...

CONCLUSION: These results demonstrated that plasma metabolomics, particularly amino acid and lipid metabolism, were associated with EAA and aging. The "cysteine and methionine metabolism" pathway emerged as a potential mechanism of aging, and may underpin metabolic alterations during the aging process, and its metabolites, such as methionine, 5-methylthioadenosine, and α-ketobutyrate, may serve as intervention targets.

This study examines the relationship between depression and clinical functioning among cognitively normal (CN) and mildly cognitively impaired (MCI) older adults, with a specific focus on cross-ethnic comparisons between Hispanic and White non-Hispanic (WNH) populations. Despite a significant body of research linking depression to cognitive decline, limited studies have explored how this relationship differs across ethnic groups. Using data from the 1Florida Alzheimer's Disease Research Center...

CONCLUSIONS: Among older adults in China, lifestyles only mediate a small proportion of frailty disparities in overall survival; consequently, without direct interventions for frailty or additional favorable measures, promoting healthy lifestyles alone is insufficient to significantly reduce frailty disparities in survival. Furthermore, individuals of frailty and unhealthy lifestyles experience significantly shorter survival, highlighting the urgent need for targeted interventions for this...

CONCLUSION: This study offers a culturally nuanced understanding of AIP, challenging the notion that 'place' is solely a physical or geographical location. It highlights the significance of social connectedness, emotional security, digital participation, and the desire to avoid institutional care. These findings provide valuable insights for policymakers and practitioners, underscoring the need to design ageing policies and care practices that address not only physical housing but also social...

Sophisticated bots risk contaminating surveys, games, and other approaches designed to shed light on human behavior

During deep co-evolution of viruses and host cells, viruses have selected specific host cellular proteins redirected from physiological functions to viral needs, thereby disturbing cellular proteostasis and increasing the risk of triggering protein misfolding diseases (PMDs). Identifying virus-specific, repurposed host proteins also allows the study of fundamental cellular events in "sporadic" PMDs, independent of the virus. Here, we identify a small molecule with very strong activity against...

Parkinson's disease (PD) patients show gait and motor timing impairments that can be improved with different behavioral therapies. This study involved an intervention with seventeen PD patients utilizing a pre-training-training-post-training protocol. The experimental paradigm included a march-in-place task (MPT) and an auditory synchronization-continuation stepping task (SCT). During these tasks, their foot movements were tracked with an infrared motion-capture system. In addition, patients...

Parkinson's Disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), which is associated with changes in microglia function. While age remains the biggest risk factor, the underlying molecular cause of PD onset and its concurrent neuroinflammation are not well understood. Many identified PD risk genes have been directly linked to dopamine neuron impairment, while others are linked to immune cell function. In this study, we found that the PD...

Black rice diets are enriched with unsaturated fatty acids that are thought to be beneficial for neurodegenerative disorders in aging. Here we find that α-linolenic acid (ALA) and 11,14-eicosadienoic acid (EDA), which are naturally enriched in black rice, inhibit amyloid pathology, rescue cognition and extend lifespan in mouse preclinical models of Alzheimer's disease via allosteric activation of G protein-coupled receptor 120 (GPR120) in plaque-associated macrophages and activated microglia. We...

Progressive neuronal loss and brain atrophy are principal determinants of cognitive decline in Alzheimer's disease (AD), yet most mouse models fail to recapitulate these features. Here we identify cyclin-dependent kinase 3 (CDK3) as a key driver of neurodegeneration in AD. CDK3 is elevated in human AD brains and correlates with disease severity. As laboratory mice carry a nonfunctional Cdk3 mutation, we generated two models with restored CDK3 activity and then crossed to AD backgrounds. Both...

With therapeutic progress in Alzheimer's disease (AD), more molecular and mechanistic targets are coming into focus. Beyond amyloid, emerging targets include tau, neuroinflammation and neurotransmitters. Targeting neuroinflammation in neurodegenerative diseases has been explored using cyclooxygenase inhibitors, but it has mostly been unsuccessful. Among the drug classes under investigation for AD are the glucagon-like peptide-1 receptor agonists (GLP-1RAs), which are approved for the treatment...