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Understanding the influence of TLR-mediated immune system on necroptosis-induced neurodegeneration in Parkinson's disease
Neurodegeneration is a hallmark of various neurological disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), stroke, and neurotropic viral infections. Although the precise etiology remains unclear, multiple pathological mechanisms contribute to disease progression, including mitochondrial dysfunction, protein aggregation, calcium excitotoxicity, endoplasmic reticulum (ER) stress, oxidative stress, immune system activation, and neuroinflammation. Among these, the immune...
Parkinson's disease in Malawi: A cross-sectional Study of clinical profiles and risk factors
Malawi is undergoing demographic shifts in age that will inevitably increase the prevalence of neurodegenerative disorders like Parkinson s disease (PD). However, there is a knowledge gap about the clinical profiles of patients with PD in the country. This cross-sectional study analyzed the clinical characteristics of thirty-two patients with PD at Queen Elizabeth Central Hospital in Blantyre Malawi using a structured questionnaire and the Movement Disorder Society Unified PD Rating Scale. The...
Prevalent mesenchymal drift in aging and disease is reversed by partial reprogramming
The loss of cellular and tissue identity is a hallmark of aging and numerous diseases, but the underlying mechanisms are not well understood. Our analysis of gene expression data from over 40 human tissues and 20 diseases reveals a pervasive upregulation of mesenchymal genes across multiple cell types, along with an altered composition of stromal cell populations, denoting a "mesenchymal drift" (MD). Increased MD correlates with disease progression, reduced patient survival, and an elevated...
Change in social isolation and risk of frailty among older adults: results from two prospective cohorts
CONCLUSIONS: Changes in social isolation are significantly associated with the incidence of frailty in older adults.
Biomarkers of multimorbidity: A systematic review
The development of multiple chronic diseases in the same individual (i.e., multimorbidity) results from the loss of homeostasis across several biological systems. Identifying pathophysiological pathways common to multiple diseases, using accessible biomarkers, could increase our understanding of multimorbidity and improve its prognostication and management. We conducted a systematic review of peer-reviewed articles published till September 2024 that investigated biomarkers of multimorbidity. Due...
L-deprenyl extends lifespan across mammalian species: A meta-analysis of 22 longevity experiments
Identifying interventions that reproducibly extend lifespan is a central aim in geroscience, with hopes of translating these findings to enhance the health and longevity of older adults. L-deprenyl, an FDA approved medication, has been investigated for its role in aging for over three decades. To evaluate the effect of L-deprenyl on lifespan in mammals we performed a random-effects meta-analysis on 22 rodent lifespan experiments. The results indicate L-deprenyl significantly increases average...
Light phase feeding and estradiol reverse ovariectomy-induced alterations in metabolism and liver clock gene expression in rat
During aging, the decline in ovarian hormone levels in women is associated with increased weight gain, fat accumulation, and alterations in the circadian timing system. Aligning eating with the activity phase improves metabolic outcomes. In contrast, misalignment entrains the circadian clock in peripheral organs and raises spontaneous locomotor activity (SLA) before mealtime. Given that ovarian estradiol (E2) modulates both metabolism and circadian function, this study aimed to investigate the...
Conserved nucleocytoplasmic density homeostasis drives cellular organization across eukaryotes
The confinement of macromolecules has profound implications for cellular biochemistry. It generates environments with specific physical properties affecting diffusion, macromolecular crowding, and reaction rates. Yet, it remains unknown how intracellular density distributions emerge and affect cellular physiology. Here, we show that the nucleus is less dense than the cytoplasm and that living systems establish a conserved density ratio between these compartments due to a pressure balance across...
Lower diet quality accelerates DNA methylation-based age
A new DNA methylation biomarker, Dunedin Pace of Aging Calculated from the Epigenome (DunedinPACE), is associated with healthy lifespan in several European ancestry cohorts. Few studies have examined the relation between dietary quality and DunedinPACE in African American and White adults with longitudinal assessments. To assess the relationship between diet quality and DunedinPACE, we used longitudinal data from African American and White 30-64 year old adults living above and below poverty....
BrainAGE in superagers: cross-sectional and longitudinal analyses in older adults aged 80+ with youthful episodic memory
Episodic memory, the ability to recall past events, is particularly vulnerable to ageing. A decline in episodic memory performance is generally considered part of ageing. However, the episodic memory performance of superagers -defined as individuals aged 80+ years old with episodic memory of people 30 years younger- is superior to that typical of their chronological age. The aim of this study was to determine whether the discrepancy between the superager's episodic memory and chronological age...
Anisotropy reveals contact sliding and aging as a cause of post-seismic velocity changes
Rocks exhibit astonishing time-dependent mechanical properties, like memory of experienced stress or slow dynamics, a transient recovery of stiffness after a softening induced by almost any type of loading. This softening and transient recovery is observed in the subsurface and in buildings after earthquakes, or in laboratory samples. Here, we investigate the anisotropy of nonlinear elastic effects in a sandstone sample under uniaxial loading. We report that slow dynamics is observed...
Alpha-synuclein abundance and localization are regulated by the RNA-binding protein PUMILIO1
The protein α-synuclein, encoded by SNCA, accumulates in Parkinson's disease (PD) and other synucleinopathies for reasons that remain unclear. Here, we investigated whether SNCA is regulated in vivo by the RNA-binding protein PUM1. We establish that PUM1 binds to SNCA's 3' UTR in mouse and human cells. In induced neurons from patients with SNCA locus triplication, PUM1 mRNA levels are lower than in healthy controls, but increasing PUM1 normalizes both SNCA mRNA and α-synuclein protein levels,...
Mineralogical controls of the oceanic nickel cycle
Transition metals and their isotopes are promising paleo-productivity proxies, but their utility depends on understanding their cycling between sediment and seawater. Using nickel (Ni) as an example, we show how manganese (Mn) minerals control its isotopic composition in oxic marine sediments. By analysing synthetic and natural samples, and simulating sediment diagenesis, we find that most Ni isotope variability in modern Mn-rich sediments is driven by the relative contribution of two bonding...
Quantitative assessment of asymptomatic spinal cord compression using MRI: a multi-center study
Aging is associated with an increased risk of neurodegenerative conditions, including degenerative cervical myelopathy (DCM), a leading cause of neurological disability in older adults. Asymptomatic spinal cord compression (ASCC) represents a potential precursor to DCM, characterized by spinal cord compression in individuals without overt clinical symptoms. Early identification and quantification of ASCC are critical for preventing age-related neurological decline. However, a standardized...
Frailty phenotype state transitions among older adults with a history of cancer and diabetes
CONCLUSIONS: Diabetes and cancer were both associated with an increased frailty prevalence; however, only older adults with diabetes or cooccurring diabetes and cancer had an increased 9-year incidence of frailty relative to older adults without a history of either condition. Future research should explore the underlying mechanisms driving frailty state transitions among chronic disease populations and evaluate targeted interventions to mitigate frailty progression.
Fostering active aging in older adults: results of a communication and social skills program
CONCLUSION: This study contributes valuable evidence supporting psychosocial interventions for active aging. To advance this field, further research should focus on the long-term impact, cultural adaptability, and multimodal strategies that comprehensively address physical, cognitive, and social domains.
T-CLASS: An Online Tool for the Identification and Classification of Aging and Senescence Using Transcriptome Data
Transcriptome analysis has become increasingly utilized in aging research. However, the identification of the key molecular changes underlying aging processes and longevity-promoting regimens from transcriptome data remains challenging. Here, we present Transcriptomic CLassification via Adaptive learning of Signature States (T-CLASS), an online tool that identifies, from transcriptome data, gene sets of several hundred genes that provide an optimal representation of longevity and aging...