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Olfactory deficit and gastrointestinal dysfunction precede motor abnormalities in alpha-Synuclein G51D knock-in mice

1 week 5 days ago
Parkinson's disease (PD) is typically a sporadic late-onset disorder, which has made it difficult to model in mice. Several transgenic mouse models bearing mutations in SNCA, which encodes alpha-Synuclein (α-Syn), have been made, but these lines do not express SNCA in a physiologically accurate spatiotemporal pattern, which limits the ability of the mice to recapitulate the features of human PD. Here, we generated knock-in mice bearing the G51D SNCA mutation. After establishing that their motor...
YoungDoo Kim

Ageing, proteostasis, and the gut: Insights into neurological health and disease

1 week 5 days ago
Recent research has illuminated the profound bidirectional communication between the gastrointestinal tract and the brain, furthering our understanding of neurological ailments facilitating possible therapeutic strategies. Technological advancements in high-throughput sequencing and multi-omics have unveiled significant alterations in gut microbiota and their metabolites in various neurological disorders. This review provides a thorough analysis of the role of microbiome-gut-brain axis in...
Mahmood Akbar

Mechanistic target of rapamycin (mTOR) pathway in Sertoli cells regulates age-dependent changes in sperm DNA methylation

1 week 5 days ago
Over the past several decades, a trend toward delayed childbirth has led to increases in parental age at the time of conception. Sperm epigenome undergoes age-dependent changes increasing risks of adverse conditions in offspring conceived by fathers of advanced age. The mechanism(s) linking paternal age with epigenetic changes in sperm remain unknown. The sperm epigenome is shaped in a compartment protected by the blood-testes barrier (BTB) known to deteriorate with age. Permeability of the BTB...
Saira Amir

Senoinflammation as the underlying mechanism of aging and its modulation by calorie restriction

1 week 5 days ago
Senoinflammation is characterized by an unresolved low-grade inflammatory process that affects multiple organs and systemic functions. This review begins with a brief overview of the fundamental concepts and frameworks of senoinflammation. It is widely involved in the aging of various organs and ultimately leads to progressive systemic degeneration. Senoinflammation underlying age-related inflammation, is causally related to metabolic dysregulation and the formation of senescence-associated...
Sang Gyun Noh

Ageing, proteostasis, and the gut: Insights into neurological health and disease

1 week 5 days ago
Recent research has illuminated the profound bidirectional communication between the gastrointestinal tract and the brain, furthering our understanding of neurological ailments facilitating possible therapeutic strategies. Technological advancements in high-throughput sequencing and multi-omics have unveiled significant alterations in gut microbiota and their metabolites in various neurological disorders. This review provides a thorough analysis of the role of microbiome-gut-brain axis in...
Mahmood Akbar

Age-related brain-region-specific changes in diffusion anisotropy in subarachnoid space of young adults

1 week 5 days ago
The glymphatic system theory postulates that brain waste is removed through the cerebrospinal fluid (CSF) flow. According to this theory, CSF in the subarachnoid space (SAS) moves to the perivascular space around the penetrating arteries, flows into parenchyma to mix with interstitial fluid and brain waste, and then moves to the perivenous space to be flushed out of the brain. Despite the controversies about the glymphatic theory, it is clear that SAS plays a key role in waste clearance. For...
Yujin Jung

Regional patterns of human cortex development correlate with underlying neurobiology

1 week 5 days ago
Human brain morphology undergoes complex changes over the lifespan. Despite recent progress in tracking brain development via normative models, current knowledge of underlying biological mechanisms is highly limited. We demonstrate that human cortical thickness development and aging trajectories unfold along patterns of molecular and cellular brain organization, traceable from population-level to individual developmental trajectories. During childhood and adolescence, cortex-wide spatial...
Leon D Lotter

Non-cell-autonomous regulation of germline proteostasis by insulin/IGF-1 signaling-induced dietary peptide uptake via PEPT-1

1 week 5 days ago
Gametogenesis involves active protein synthesis and is proposed to rely on proteostasis. Our previous work in C. elegans indicates that germline development requires coordinated activities of insulin/IGF-1 signaling (IIS) and HSF-1, the central regulator of the heat shock response. However, the downstream mechanisms were not identified. Here, we show that depletion of HSF-1 from germ cells impairs chaperone gene expression, causing protein degradation and aggregation and, consequently, reduced...
Tahir Muhammad

Challenges and recommendations for the translation of biomarkers of aging

1 week 5 days ago
Biomarkers of aging (BOA) are quantitative parameters that predict biological age and ideally its changes in response to interventions. In recent years, many promising molecular and omic BOA have emerged with an enormous potential for translational geroscience and improving healthspan. However, clinical translation remains limited, in part due to the gap between preclinical research and the application of BOA in clinical research and other translational settings. We surveyed experts in these...
Biomarkers of Aging Consortium

Contribution of A1 to macrophage survival in cooperation with MCL-1 and BCL-X<sub>L</sub> in a murine cell model of myeloid differentiation

1 week 5 days ago
Myeloid cells are the first line of defence against pathogens. Mitochondrial apoptosis signalling is a crucial regulator of myeloid cell lifespan and modulates the function of myeloid cells. The anti-apoptotic protein BCL-2-family protein BCL2A1/A1/BFL-1 is strongly upregulated in inflammation in macrophages. We analysed the contribution of A1 to apoptosis regulation in a conditional system of in vitro differentiation of murine macrophages from immortalised progenitors. We disabled the...
Juliane Vier

Fundamental equations linking methylation dynamics to maximum lifespan in mammals

1 week 5 days ago
We describe a framework that addresses concern that the rate of change in any aging biomarker displays a trivial inverse relation with maximum lifespan. We apply this framework to methylation data from the Mammalian Methylation Consortium. We study the relationship of lifespan with the average rate of change in methylation (AROCM) from two datasets: one with 90 dog breeds and the other with 125 mammalian species. After examining 54 chromatin states, we conclude three key findings: First, a...
Steve Horvath