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Machine learning reveals prominent spontaneous behavioral changes and treatment efficacy in humanized and transgenic Alzheimer's disease models

2 months ago
Computer-vision and machine-learning (ML) approaches are being developed to provide scalable, unbiased, and sensitive methods to assess mouse behavior. Here, we used the ML-based variational animal motion embedding (VAME) segmentation platform to assess spontaneous behavior in humanized App knockin and transgenic APP models of Alzheimer's disease (AD) and to test the role of AD-related neuroinflammation in these behavioral manifestations. We found marked alterations in spontaneous behavior in...
Stephanie R Miller

Mitochondria break free: Mitochondria-derived vesicles in aging and associated conditions

2 months ago
Mitophagy is the intracellular recycling system that disposes damaged/inefficient mitochondria and allows biogenesis of new organelles to ensure mitochondrial quality is optimized. Dysfunctional mitophagy has been implicated in human aging and diseases. Multiple evolutionarily selected, redundant mechanisms of mitophagy have been identified, but their specific roles in human health and their potential exploitation as therapeutic targets are unclear. Recently, the characterization of the...
Luigi Ferrucci

Rodent model intervention for prevention and optimal management of sarcopenia: A systematic review on the beneficial effects of nutrients & non-nutrients and exercise to improve skeletal muscle health

2 months ago
Sarcopenia is a common musculoskeletal disorder characterized by degenerative processes and is strongly linked to an increased susceptibility to falls, fractures, physical limitations, and mortality. Several models have been used to explore therapeutic and preventative measures as well as to gain insight into the molecular mechanisms behind sarcopenia. With novel experimental methodologies emerging to design foods or novel versions of conventional foods, understanding the impact of nutrition on...
Vijayakumar Mayakrishnan

HMGB1, an evolving pleiotropic protein critical for cellular and tissue homeostasis: Role in aging and age-related diseases

2 months ago
Aging is a universal biological process characterized by a progressive, cumulative decline in homeostatic capabilities and physiological functions, which inevitably increases vulnerability to diseases. A number of molecular pathomechanisms and hallmarks of aging have been recognized, yet we miss a thorough understanding of their complex interconnectedness. This review explores the molecular and cellular mechanisms underlying human aging, with a focus on the multiple roles of high mobility group...
Elena Ruggieri

Hallmarks of a genomically distinct subclass of head and neck cancer

2 months ago
Cancer is caused by an accumulation of somatic mutations and copy number alterations (CNAs). Besides mutations, these copy number changes are key characteristics of cancer development. Nonetheless, some tumors show hardly any CNAs, a remarkable phenomenon in oncogenesis. Head and neck squamous cell carcinomas (HNSCCs) arise by either exposure to carcinogens, or infection with the human papillomavirus (HPV). HPV-negative HNSCCs are generally characterized by many CNAs and frequent mutations in...
Tara Muijlwijk

RNA G-quadruplexes form scaffolds that promote neuropathological α-synuclein aggregation

2 months 1 week ago
Synucleinopathies, including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, are triggered by α-synuclein aggregation, triggering progressive neurodegeneration. However, the intracellular α-synuclein aggregation mechanism remains unclear. Herein, we demonstrate that RNA G-quadruplex assembly forms scaffolds for α-synuclein aggregation, contributing to neurodegeneration. Purified α-synuclein binds RNA G-quadruplexes directly through the N terminus. RNA G-quadruplexes...
Kazuya Matsuo

Expansion of the neocortex and protection from neurodegeneration by in vivo transient reprogramming

2 months 1 week ago
Yamanaka factors (YFs) can reverse some aging features in mammalian tissues, but their effects on the brain remain largely unexplored. Here, we induced YFs in the mouse brain in a controlled spatiotemporal manner in two different scenarios: brain development and adult stages in the context of neurodegeneration. Embryonic induction of YFs perturbed cell identity of both progenitors and neurons, but transient and low-level expression is tolerated by these cells. Under these conditions, YF...
Yi-Ru Shen

Expansion of the neocortex and protection from neurodegeneration by in vivo transient reprogramming

2 months 1 week ago
Yamanaka factors (YFs) can reverse some aging features in mammalian tissues, but their effects on the brain remain largely unexplored. Here, we induced YFs in the mouse brain in a controlled spatiotemporal manner in two different scenarios: brain development and adult stages in the context of neurodegeneration. Embryonic induction of YFs perturbed cell identity of both progenitors and neurons, but transient and low-level expression is tolerated by these cells. Under these conditions, YF...
Yi-Ru Shen

ASI-RIM neuronal axis regulates systemic mitochondrial stress response via TGF-β signaling cascade

2 months 1 week ago
Morphogens play a critical role in coordinating stress adaptation and aging across tissues, yet their involvement in neuronal mitochondrial stress responses and systemic effects remains unclear. In this study, we reveal that the transforming growth factor beta (TGF-β) DAF-7 is pivotal in mediating the intestinal mitochondrial unfolded protein response (UPR^(mt)) in Caenorhabditis elegans under neuronal mitochondrial stress. Two ASI sensory neurons produce DAF-7, which targets DAF-1/TGF-β...
Zihao Wang