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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...

CONCLUSION: The downregulation of many genes is a major contributor to brain aging and neurodegeneration. High levels of physical activity have been shown to effectively reactivate these genes, making it a promising strategy to slow brain aging.

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...

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...

Syrian researchers around the world begin to plan for the nation’s future

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...

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...

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...

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.

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...

CONCLUSION: We did not observe a meaningful association between depressive symptoms and obesity phenotypes. Also, other than malnutrition or its risk, various severities of depressive symptoms correlate with different sociodemographic and medical risk factors among male and female senior citizens.

Fatty acid oxidation is of uncertain importance in most stem cells. We show by ^(14)C-palmitate tracing and metabolomic analysis that hematopoietic stem/progenitor cells (HSPCs) engage in long-chain fatty acid oxidation that depends upon carnitine palmitoyltransferase 1a (CPT1a) and hydroxyacyl-CoA dehydrogenase (HADHA) enzymes. CPT1a or HADHA deficiency had little or no effect on HSPCs or hematopoiesis in young adult mice. Young HSPCs had the plasticity to oxidize other substrates, including...

CONCLUSIONS: Poor sleep quality is associated with increased likelihood of probable sarcopenia in older adults. This finding highlights the importance of addressing sleep quality in interventions aimed at preventing sarcopenia and promoting healthy aging.

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This special issue of the Journal of Experimental Gerontology explores the dynamic interplay between microbiomes and aging-related conditions. The four selected studies highlight the role of microbiota in Alzheimer's disease, cancer immunotherapy, myocardial infarction and tryptophan metabolism, providing insights into how microbiomes influence health and disease in aging. These studies underscore the potential for microbiome-targeted interventions to mitigate aging-related disorders and improve...

CONCLUSIONS: Fewer functional teeth were associated with low physical function in older adults. Our results emphasize the importance of maintaining adequate functional teeth to preserve physical function in community-dwelling older adults.