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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...

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)....

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...

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.

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)....

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...

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...

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...

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...

CONCLUSIONS: Our framework establishes a powerful new paradigm for epigenetic research that can be extended to other complex diseases, offering both a valuable tool for variant effect interpretation and a promising strategy for uncovering novel disease mechanisms through epigenetic profiling.

In the context of cognitive neuroscience research on aging, older women are often overrepresented in observational research, whereas men are overrepresented in clinical trials. Factors underlying the selection bias between and across genders in research on aging are currently poorly understood. Addressing this knowledge gap is critical to provide guidance on how we might mitigate selection bias and improve the generalizability, robustness, and reproducibility of our findings. We aimed to...

Adiponectin is an adipose tissue-derived peptide hormone that exerts beneficial metabolic effects in many tissues throughout the body. It is most well-known for its ability to enhance insulin sensitivity and dampen chronic inflammation. The impact of age on adiponectin is controversial; levels of adiponectin in circulation in older individuals have been linked to both positive and negative effects. This review integrates genetic, mechanistic, and therapeutic perspectives on adiponectin in aging....

The abundance, dynamics, and context-dependent heterogeneity of DNA methylation, where a pattern considered abnormal in one cell type may be normal in another, complicate the identification of early methylation changes that drive or signal disease development. This complexity can obscure early markers of increased disease risk, making it challenging to detect and intervene in disease processes at their inception. Here, we report 31,744 CpG loci exhibiting highly consistent methylation profiles...

Extracellular vesicles (EVs) are key mediators of intercellular communication and may reflect physiological changes during aging. We analyzed plasma-derived EVs from a healthy aging cohort stratified by age, using size exclusion chromatography, surface profiling, nanoparticle tracking, and small RNA sequencing. While EV size and concentration remained largely unchanged, older individuals showed shifts in EV immunophenotype consistent with immunosenescence and displayed distinct miRNA signatures...

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ObjectivesPhysical health often declines with age, yet subjective well-being (SWB) tends to remain stable. Stereotype Embodiment Theory proposes that internalized self-perceptions of aging (SPAs) shape how physical changes are interpreted. This study tested whether SPA buffered the affective impact of health decline. The role of SPA was tested in midlife and late adulthood.MethodsData came from the ILSE, a population-based study of 1,002 adults initially aged 40 or 60 and followed for 20 years....