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Broadscale dampening of uncertainty adjustment in the aging brain

8 months 3 weeks ago
The ability to prioritize among input features according to relevance enables adaptive behaviors across the human lifespan. However, relevance often remains ambiguous, and such uncertainty increases demands for dynamic control. While both cognitive stability and flexibility decline during healthy ageing, it is unknown whether aging alters how uncertainty impacts perception and decision-making, and if so, via which neural mechanisms. Here, we assess uncertainty adjustment across the adult...
Julian Q Kosciessa

Perceptions, opportunities and barriers of social engagement among the Chinese older adults: a qualitative study

8 months 3 weeks ago
CONCLUSION: The social engagement of the older adults in urban China reflects and is influenced by the wider socio-economic transformation of the country in the recent decades. Financial security afforded by the pension system has lessened the older adults' need to engage in income-generating activities. Combined with an increase in leisure time, this represents a luxury previously unavailable to earlier generations. However, institutional ageism and low digital literacy are important...
Jining Li

Neuronal constitutive endolysosomal perforations enable α-synuclein aggregation by internalized PFFs

8 months 3 weeks ago
Endocytosis, required for the uptake of receptors and their ligands, can also introduce pathological aggregates such as α-synuclein (α-syn) in Parkinson's Disease. We show here the unexpected presence of intrinsically perforated endolysosomes in neurons, suggesting involvement in the genesis of toxic α-syn aggregates induced by internalized preformed fibrils (PFFs). Aggregation of endogenous α-syn in late endosomes and lysosomes of human iPSC-derived neurons (iNs), seeded by internalized α-syn...
Anwesha Sanyal

Base editing of Ptbp1 in neurons alleviates symptoms in a mouse model of Parkinson's disease

8 months 3 weeks ago
Parkinson's disease (PD) is a multifactorial disease caused by irreversible progressive loss of dopaminergic neurons (DANs). Recent studies have reported the successful conversion of astrocytes into DANs by repressing polypyrimidine tract binding protein 1 (PTBP1), which led to the rescue of motor symptoms in a chemically-induced mouse model of PD. However, follow-up studies have questioned the validity of this astrocyte-to-DAN conversion model. Here, we devised an adenine base editing strategy...
Desiree Böck

Impairment of lipid homeostasis causes lysosomal accumulation of endogenous protein aggregates through ESCRT disruption

8 months 3 weeks ago
Protein aggregation increases during aging and is a pathological hallmark of many age-related diseases. Protein homeostasis (proteostasis) depends on a core network of factors directly influencing protein production, folding, trafficking, and degradation. Cellular proteostasis also depends on the overall composition of the proteome and numerous environmental variables. Modulating this cellular proteostasis state can influence the stability of multiple endogenous proteins, yet the factors...
John Yong

EEG brain networks modulation during sleep onset: the effects of aging

8 months 3 weeks ago
The aim of the present study is to investigate differences in brain networks modulation during the pre- and post-sleep onset period, both within and between two groups of young and older individuals. Thirty-six healthy elderly and 40 young subjects participated. EEG signals were recorded during pre- and post-sleep onset periods and functional connectivity analysis, specifically focusing on the small world (SW) index, applied to EEG data (i.e., frequency bands) was examined. Significant...
Francesca Miraglia

Variation in brain aging: A review and perspective on the utility of individualized approaches to the study of functional networks in aging

8 months 4 weeks ago
Healthy aging is associated with cognitive decline across multiple domains, including executive function, memory, and attention. These cognitive changes can often influence an individual's ability to function and quality of life. However, the degree to which individuals experience cognitive decline, as well as the trajectory of these changes, exhibits wide variability across people. These cognitive abilities are thought to depend on the coordinated activity of large-scale networks. Like...
Diana C Perez

A novel 14mer peptide, T14, is associated with age-dependent behaviour in female mice

8 months 4 weeks ago
Age-related cognitive decline presents a healthcare challenge. While age-related mechanisms are mainly studied in humans, animal models provide key insights. Despite evidence of sex-specific differences in aging and cognition, the impact of age on female rodent behaviour is underexplored. This study investigated age-related behavioural changes in female C57BL/6 mice over 8 months, alongside neurochemical markers amyloid, Tau, and T14, a novel peptide from acetylcholinesterase (AChE) that...
Sibah Hasan

The interplay of NAD and hypoxic stress and its relevance for ageing

8 months 4 weeks ago
Nicotinamide adenine dinucleotide (NAD) is an essential regulator of cellular metabolism and redox processes. NAD levels and the dynamics of NAD metabolism change with increasing age but can be modulated via the diet or medication. Because NAD metabolism is complex and its regulation still insufficiently understood, achieving specific outcomes without perturbing delicate balances through targeted pharmacological interventions remains challenging. NAD metabolism is also highly sensitive to...
Johannes Burtscher

Development and Validation of a Nutritional Frailty Phenotype for Older Adults Based on Risk Prediction Model: Results From a Population-Based Prospective Cohort Study

8 months 4 weeks ago
CONCLUSIONS AND IMPLICATIONS: A novel nutritional frailty phenotype may have direct implications for decreasing risk of adverse outcomes in older adults. Weakness and slowness play a major role in the progression of nutritional frailty, emphasizing that nutritional supplementation combined with exercise may be one of the feasible pathways to prevent or delay adverse outcomes.
Hongpeng Liu

A unique inflammaging profile generated by T cells from people with obesity is metformin resistant

8 months 4 weeks ago
The alarmingly high prevalence of obesity in older adults coupled with the negative health effects of chronic inflammation in both obesity and aging highlight the importance of studies investigating the impacts of obesity on age-related inflammation. Since shifts in peripheral T-cell metabolism and function drive systemic inflammation in both obesity and aging, we hypothesize that obesity impacts the Th17-dominated inflammaging profile we identified in lean subjects and thus modifies the...
S SantaCruz-Calvo