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Neuroprotective effects of idebenone in a zebrafish model of Parkinson's disease via regulating autophagy, mitigating apoptosis and oxidative stress

2 months 1 week ago
Idebenone (IDE), an analog of ubiquinone, has demonstrated therapeutic potential across various neurodegenerative disorders. Clinically, IDE has been shown to exert neuroprotective effects in Parkinson's disease (PD), being capable of alleviating motor symptoms as well as reducing depressive and anxious moods. However, the mechanism of action of IDE in PD has not been fully elucidated. Thus, the present study aims to investigate the potential effects of IDE on...
Yanqing Zhang

Mitochondrial double-stranded RNA drives aging-associated cognitive decline

2 months 1 week ago
Aging is the primary cause of cognitive decline. Despite extensive study, the molecular mechanisms driving aging-associated cognitive decline remain unclear. Here, we describe a proteostasis-independent function of SEC61A1 and its involvement in aging-associated cognitive decline. SEC61A1 regulates ER-mitochondria contact sites, affecting mitochondrial DNA and RNA synthesis and subsequently leading to changes in innate immune signaling mediated by mitochondrial double-stranded RNA (mt-dsRNA)....
Lixiao Zhang

Long-Term Care as a Global Challenge: The Role of the World Health Organization

2 months 1 week ago
Long-term care is today one of the most pressing issues in public policy. Its relevance is increasing everywhere but mostly, due to population aging, in low- and middle-income countries. Despite the advances in the past decades regarding the implementation of long-term care systems in several countries, the COVID-19 pandemic showed their fragility and called to rethink long-term care around the world. Issues like quality, workforce shortages, and financial sustainability are key in countries...
Pablo Villalobos Dintrans

Harmonization of late-life participation in cognitively stimulating activities across four cohort studies of cognitive aging

2 months 1 week ago
CONCLUSION: We statistically harmonized survey data measuring frequency of participation in cognitive activities across four studies of aging and subsequently validated the harmonized latent trait by linking it to ADRD outcomes. Findings demonstrate the utility of combining self-reported psychosocial survey data collected across multiple studies to thoroughly evaluate the impact of modifiable risk factors on later-life cognitive outcomes in heterogeneous populations.
A R Zammit

Mitochondrial double-stranded RNA drives aging-associated cognitive decline

2 months 1 week ago
Aging is the primary cause of cognitive decline. Despite extensive study, the molecular mechanisms driving aging-associated cognitive decline remain unclear. Here, we describe a proteostasis-independent function of SEC61A1 and its involvement in aging-associated cognitive decline. SEC61A1 regulates ER-mitochondria contact sites, affecting mitochondrial DNA and RNA synthesis and subsequently leading to changes in innate immune signaling mediated by mitochondrial double-stranded RNA (mt-dsRNA)....
Lixiao Zhang

Subtype-specific sirtuin expression signatures link mitochondrial-epigenetic networks to breast cancer survival

2 months 1 week ago
Sirtuins (SIRT1-SIRT7) are NAD⁺-dependent regulators of mitochondrial metabolism, chromatin remodeling, and stress resilience pathways-processes that are central to both aging biology and breast cancer (BC) heterogeneity. We systematically evaluated their prognostic and transcriptional patterns across molecular subtypes of BC. We constructed an integrated BC dataset comprising gene expression and survival data containing tumors from 55 datasets. Prognostic associations with recurrence-free...
Zoltan Ungvari

Breaking the Bonds of Aging: The Underappreciated Roles of Aberrant Cysteine Crosslinks and Protective Thiol Interventions

2 months 1 week ago
Aging is a complex process characterized by the accumulation of molecular damage that leads to cellular dysfunction and tissue deterioration. Among the various types of contributing molecular damage, aberrant protein crosslinks are recognized as a key contributor to age-related pathologies. Crosslinks occurring at lysine and arginine residues, such as advanced glycation end-products (AGEs) and carbamylation, have attracted considerable attention of the aging research community. In contrast, the...
Sheila N Duong

Combining xQTL and genome-wide association studies from diverse populations improves druggable gene discovery

2 months 1 week ago
Repurposing existing medicines to target disease-associated genes represents a promising strategy for developing effective treatments for complex diseases. However, progress has been hindered by a lack of viable candidate drug targets identified through genome-wide association studies. Gene-based association tests provide a more powerful alternative to traditional SNP-based methods, yet current approaches often fail to leverage shared heritability across populations and to effectively integrate...
Noah Lorincz-Comi

Genetic risk in Alzheimer's disease

2 months 1 week ago
Alzheimer's disease (AD) has a strong genetic predisposition. Genome-wide association studies have identified multiple risk loci, yet many non-coding variants remain uncharacterized. Machine learning-based polygenic risk scores (PRS) enhance prediction by modeling genetic epistasis and sex-specific risks. This review summarizes AD genetic risk factors, PRS methodologies, and ML-based AD risk prediction. It also highlights challenges such as population bias, functional validation, and integrating...
Yining Pan