Aggregator

Machine learning can unravel heterogeneous patterns of brain aging and neurodegeneration, but existing methods offer limited insights into disease progression due to reliance on cross-sectional data. We introduce Coupled Cross-sectional and Longitudinal Non-negative Matrix Factorization (CCL-NMF) to capture dominant brain aging patterns by simultaneously leveraging cross-sectional and longitudinal neuroimaging data. CCL-NMF allows individuals to co-express multiple patterns, capturing mixed...

Aberrant activation of the classical complement pathway in the brain is implicated in contributing to synapse loss and neurodegeneration in various neurodegenerative conditions. Given that C3aR is a druggable target in the complement pathway, we evaluated the potential of C3aR knockout (KO) to rescue neurodegeneration in a tauopathy model and neuroinflammatory responses in an acute endotoxemia model. We found that C3aR KO did not rescue Tau pathology, microglia activation markers,...

The existence and functional significance of immature neurons in the adult human brain, particularly in the context of neurodegenerative disorders, remain an open question. Although rodent studies have highlighted active roles for adult-born immature neurons in the hippocampus both under healthy conditions and in Alzheimer's disease (AD), evidence from the human brain is limited and lacks detailed molecular characterization. To address this gap, we performed single-nucleus RNA sequencing in aged...

CONCLUSIONS: About four in five older Brazilians meeting dementia criteria had no prior clinical diagnosis, with marked sociodemographic and regional disparities. Both individual factors-such as age, education, and multimorbidity-and structural inequities across regions influenced diagnostic likelihood. Strengthening early-detection strategies, improved health professional training, and regionally tailored approaches may improve recognition of dementia in Brazil's public health system.

The existence and functional significance of immature neurons in the adult human brain, particularly in the context of neurodegenerative disorders, remain an open question. Although rodent studies have highlighted active roles for adult-born immature neurons in the hippocampus both under healthy conditions and in Alzheimer's disease (AD), evidence from the human brain is limited and lacks detailed molecular characterization. To address this gap, we performed single-nucleus RNA sequencing in aged...

Recent studies report that epithelial differentiated cells can undergo a reverse process called dedifferentiation in response to stem cell loss. However, the extent of this reversion and the plasticity of young versus aged-differentiated cells remain unclear. Here we show that dedifferentiated corneal epithelial cells acquire a transcriptomic state closely resembling native stem cells, sustain tissue homeostasis across lifespan and efficiently repair repeated tissue injury. Transplantation of...

Cellular senescence plays a significant role in age-related conditions like osteoarthritis (OA) and intervertebral disc degeneration, in part due to the accumulation of senescent cells (SCs) in musculoskeletal tissues. Identifying novel therapeutics that can clear SCs is crucial for improving musculoskeletal health in the elderly. The present study aimed to elucidate the changes in Class I histone deacetylases (HDACs) and their role during senescence. All Class I HDACs except HDAC1 were...

While exercise is shown to reduce hippocampal atrophy, the underlying molecular mechanisms remain to be fully elucidated. Animal studies suggest the myokine irisin underlies exercise-related hippocampal benefits, though human evidence is lacking. We cross-sectionally examined 74 healthy older adults (age 65.47 ± 8.56 years). Participants completed Godin Leisure-Time exercise questionnaires, provided fasting blood for irisin measurement and underwent structural MRI with hippocampal subfield...

Aging is commonly viewed as a passive consequence of accumulated damage; however, emerging evidence suggests that it may also represent an adaptive response to environmental stress. Here, we combined transcriptomic and metabolomic profiling of Saccharomyces cerevisiae to investigate how short-term, long-term, and recovery phases of stress exposure shape cellular physiology and lifespan. Short-term stress-induced protective pathways and longevity-associated metabolites, including trehalose and...

While exercise is shown to reduce hippocampal atrophy, the underlying molecular mechanisms remain to be fully elucidated. Animal studies suggest the myokine irisin underlies exercise-related hippocampal benefits, though human evidence is lacking. We cross-sectionally examined 74 healthy older adults (age 65.47 ± 8.56 years). Participants completed Godin Leisure-Time exercise questionnaires, provided fasting blood for irisin measurement and underwent structural MRI with hippocampal subfield...

Epithelial ovarian cancer (EOC) incidence and mortality increase with age, driven in part by chronic inflammation, diminished T cell output, and heightened regulatory T cell (Treg) mediated immunosuppression. In aged EOC-bearing mice, we observed reduced survival, accompanied by impaired CD4^(+) and CD8^(+) T cell responses and a marked expansion of FOXP3^(+) Tregs exhibiting elevated IL-10 and TGFβ expression. Metabolic profiling revealed enhanced oxidative phosphorylation in Tregs from aged...

Complex phenotypes, including aging, are influenced by a connected gene regulatory network with many interacting nodes. It has been proposed that some genes, termed "core genes," directly contribute to a trait, whereas "peripheral genes" influence the trait indirectly through network interactions. Yet demonstrating such a layered architecture and assigning genes to layers remains challenging. Using yeast aging, we developed an approach to infer network architecture underlying complex traits....

The transient upregulation of cellular senescence within wound tissues has been demonstrated to be an important biological process facilitating efficient tissue repair. Dysregulation of this transient wound-induced senescence response can result in impaired healing outcomes. Given the established age-related decline in tissue regenerative capacity, we hypothesized that alterations in this senescence response contribute to the delayed healing of cutaneous wounds in aged individuals. Our...

Cellular senescence and mitochondrial dysfunction are prevalent in adipose tissues and disrupt metabolic homeostasis during aging, but the mechanisms are poorly understood. Here, we investigated the role of histone deacetylase 9 (HDAC9), an epigenetic regulator of adipogenic differentiation, in aging-related adipose tissue senescence and mitochondrial dysfunction. HDAC9 expression correlated positively with age in mouse adipose tissues. Compared to age-matched wild-type (WT) mice, Hdac9 knockout...

Dismissal of the National Science Board is widely seen as latest move to erase NSF’s independence

Wearing-off (WO) is a common motor complication in Parkinson's disease (PD), characterized by the re-emergence of symptoms before the next dose of dopaminergic medication and still lacking objective, bedside-available neurophysiological biomarkers. In this study, we investigated cortical functional network alterations associated with WO using resting-state functional near-infrared spectroscopy (fNIRS), graph-theoretical analysis, and machine learning. Resting-state fNIRS signals were acquired...

Age-related neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and related dementias, are increasingly understood as multifactorial proteinopathies involving co-aggregation of amyloidogenic proteins such as Tubulin-associated unit protein (Tau), α-synuclein (α-syn), amyloid-β (Aβ), and TAR DNA-binding protein 43 (TDP-43). Rather than acting independently, these proteins often cross-seed, co-localize, and modulate each other's aggregation dynamics and...

No abstract

Aberrant activation of innate immune signaling is known to contribute to neuroinflammation in age-related neurological disorders, but the mechanisms underlying this activation remain unclear. Here, we discovered that protein S-nitrosylation, a redox-based posttranslational modification, regulates the stimulator of interferon genes (STING) protein in Alzheimer's disease (AD). Using a combination of redox chemical biology and mass spectrometry, we identified S-nitrosylation at cysteine 148 as a...

Nanoscopic aggregates of alpha-synuclein (ɑSyn) have been observed in Parkinson's disease (PD). However, the processes that occur in vivo leading to the formation of these small aggregates are not well understood. We used ultra-sensitive single-molecule methods, including single molecule array (SIMOA), and super-resolution microscopy to quantify and characterize ɑSyn aggregates harvested from human brain samples, alongside a mouse model of synucleinopathy, using different tissue processing...