Alfonso Lopez’s Post

The aging of the world’s population has intensified interest in understanding the aging process and devising strategies and interventions to prolong a healthy life span. Cellular senescence, when cells become irreversibly growth arrested after a period of in vitro cell proliferation or in response to sublethal stress or oncogene expression (1, 2), plays a role in aging phenotypes and age-associated diseases (1). Increasing evidence shows that senescent cells also have essential physiological functions, such as in tumor suppression, development, wound healing, tissue remodeling, regeneration, and vasculature. This raises important questions about the similarities and differences between senescent cell types and how they function in homeostasis and pathology, and it creates additional challenges in targeting them therapeutically.

'Prelude' to neuromuscular disease SMA may offer chances for better treatment https://lnkd.in/dsYcJByf Spinal muscular atrophy (SMA) is a severe neurological disease for which there is presently no cure, although current therapies can alleviate symptoms. In the search for better treatment options, scientists are now drawing attention to previously unnoticed abnormalities in embryonic development. They base their argument on studies of so-called organoids: Laboratory-grown tissue cultures that can reconstruct disease processes.

The Dual Nature of Cellular Senescence: Beyond Aging Recent research has shed new light on cellular senescence, revealing its complex role in both health and disease. While long associated with aging and age-related disorders, senescent cells are now understood to play crucial physiological roles throughout our lives. Key Findings: Development and Growth: Senescent cells are vital for organ development, particularly in the lungs and placenta. Tissue Repair: They promote wound healing and tissue regeneration across various species, from hydra to mammals. Homeostasis: Senescent cells maintain blood-tissue barriers and contribute to insulin secretion in pancreatic beta cells. Tumor Suppression: Their role in cancer prevention remains a critical function. However, the picture is not entirely rosy. An excessive accumulation of senescent cells can indeed contribute to age-related decline and various pathologies. Implications for Therapeutics: The dual nature of senescent cells presents a challenge for developing anti-aging therapies. Future treatments may need to be highly precise, targeting harmful senescent cells while preserving those essential for normal physiology. This evolving understanding of cellular senescence opens new avenues for research in regenerative medicine, aging, and disease prevention. It underscores the complexity of biological processes and the need for nuanced approaches in medical interventions. https://lnkd.in/dixP9a7f #AgingResearch #Biotechnology #MedicalScience

#NeuroInflammation | #NeuroDegenerativeDisease | Quantifying #Microglia Morphology: An Insight into Function | OPEN ACCESS Review by Tabitha Green & Rachel Rowe Online at British Society for Immunology Journal #CEI 👏 | Microglia are specialized immune cells unique to the central nervous system (CNS). Microglia have a highly plastic morphology that changes rapidly in response to injury or infection. Qualitative and quantitative measurements of ever-changing microglial morphology are considered a cornerstone of many microglia-centric research studies. The distinctive morphological variations seen in microglia are a useful marker of inflammation and severity of tissue damage. Although a wide array of damage-associated microglial morphologies has been documented, the exact functions of these distinct morphologies are not fully understood. In this review*, the authors discuss how microglia morphology is not synonymous with microglia function, however, morphological outcomes can be used to make inferences about microglial function. For a comprehensive examination of the reactive status of a microglial cell, both histological and genetic approaches should be combined. However, the importance of quality immunohistochemistry-based analyses should not be overlooked as they can succinctly answer many research questions. *https://lnkd.in/eE79E8Dw Celentyx Ltd #human #microglia #drugdiscovery #platforms https://lnkd.in/eMWCkkDw Professor Nicholas Barnes PhD, FBPhS Omar Qureshi Catherine Brady

🔬Scientists have discovered that as mammals age, their guts experience an imbalance and buildup of faulty🧬mitochondrial DNA (mtDNA), but we don't fully understand how this affects gut health. They studied this in older male mice👴🐁and found that their small intestines had more mtDNA mutations, suggesting a link to aging. By comparing mice bred to accumulate these mutations with regular mice, they found that increasing mtDNA mutations led to poorer gut function, including reduced ability for intestinal stem cells to regenerate. They discovered that a specific response called the mitochondrial unfolded protein response (UPRmt), triggered by these mutations, worsens gut aging. However, when they supplemented the mice with NMN💊, a substance that boosts NAD+ levels, the aging process in the gut reversed. This research shows that by understanding and targeting these molecular pathways, scientists might be able to slow down gut aging in mammals. #longevity #newresearch #antiaging #NAD+ #GutHealth #MitochondrialDNA #ScienceNews #NMN #AgingResearch https://lnkd.in/ePXin8et

#neurodegenerativedisease #trehalose #neuroprotection Profiling neuroprotective potential of trehalose in animal models of neurodegenerative diseases: a systematic review https://lnkd.in/gxsG6KXg Universiti Sains Malaysia Trehalose, a unique nonreducing crystalline disaccharide, is a potential disease-modifying treatment for neurodegenerative diseases associated with protein misfolding and aggregation due to aging, intrinsic mutations, or autophagy dysregulation. This systematic review summarizes the effects of trehalose on its underlying mechanisms in animal models of selected neurodegenerative disorders (tau pathology, synucleinopathy, polyglutamine tract, and motor neuron diseases).

Is cellular senescence to be targeted to fight #aging? Seminal studies in mice (where senescent cells are genetically ablated and life span is increased) have prompted the development of senolytic drugs. However, increasing evidence shows that senescent cells also have essential physiological functions, such as in tumor suppression, development, wound healing, tissue vascularization, remodeling and regeneration. As such, effective therapies will need the precision to eliminate pathologic senescent cells while sparing healthy senescent cells. https://lnkd.in/eZxQF_fq

STING inhibition has neuroprotective effects in a neuropathic Gaucher Disease mouse model. Biallelic GBA1 mutations, encoding b-glucocerebrosidase, lead to Gaucher disease (GD), while monoallelic mutations are a risk factor for Parkinson's disease. Glucocerebrosidase deficiency triggers systemic glucosylceramide (GlcCer) accumulation, inducing neurodegeneration. Microglial GlcCer accumulation promotes mitochondrial DNA release and subsequent STING pathway activation. This disrupts damaged mitochondrial clearance, further exacerbating neuroinflammation. Notably, treatment with a STING inhibitor in a GD mouse model demonstrated neuroprotective effects, suggesting a potential therapeutic avenue for diseases with b-glucocerebrosidase deficiency. https://lnkd.in/exbDGncx #genetics #genomics #precisionmedicine #genomicmedicine #brain #neurology #neurodegeneration #neuroscience #raredisease #gaucherdisease #parkinson #inflammation #neuroinflammation #metabolism #physiology #therapeutics #biomarkers #biotechnology #innovation #research #science #sciencecommunication

They have found a subset of neutrophils from female patients with Alzheimer’s disease (AD), carrying APOE ε4 with overexpression of IL-17 and IL-1 both in blood neutrophils and in microglia, which implies greater infiltration to the brain and an immunosuppressive state regulated by IL-10, TGFβ, and immune checkpoints (LAG3 and PD-1), all of which have been associated with accelerated immune aging. A very interesting aspect of the mouse study is that deletion of APOE ε4 in neutrophils reduced this immunosuppressive phenotype and restored the microglial response to neurodegeneration, limiting plaque pathology. https://lnkd.in/ddpe4TZk