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The cover art of the October 2013 edition of Alberta Native News is a detail from “Southwest Visit” by internationally acclaimed artist Alex Janvier. From...

Crucial for skin homeostasis, synthesis and degradation of extracellular matrix components are orchestrated by dermal fibroblasts. During aging, alterations of component expression, such as collagens and enzymes, lead to reduction of the mechanical cutaneous tension and defects of skin wound healing. The aim of this study was to better understand the molecular alterations underwent by fibroblasts during aging by comparing secretomic and proteomic signatures of fibroblasts from young (<35years) and aged (>55years) skin donors, in quiescence or TGF-stimulated conditions, using HLPC/MS. The comparison of the secretome from young and aged fibroblasts revealed that 16 proteins in resting condition, and 11 proteins after a 24h-lasting TGF-β1-treatment, were expressed in significant different ways between the two cell groups (fold change>2, p-value <0.05), with a 77% decrease in the number of secreted proteins in aged cells. Proteome comparison between young and aged fibroblasts identified a significant change of 63 proteins in resting condition, and 73 proteins in TGF-β1-stimulated condition, with a 67% increase in the number of proteins in aged fibroblasts. The majority of the differentially-expressed molecules belongs to the cytoskeleton-associated proteins and aging was characterized by an increase in Coronin 1C (CORO1C), and Filamin B (FLNB) expression in fibroblasts together with a decrease in Cofilin (CFL1), and Actin alpha cardiac muscle 1 (ACTC1) detection in aged cells, these proteins being involved in actin-filament polymerization and sharing co-activity in cell motility. Our present data reinforce knowledge about an age-related alteration in the synthesis of major proteins linked to the migratory and contractile functions of dermal human fibroblasts.

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The recent unprecedented progress in ageing research and drug discovery brings together fundamental research and clinical applications to advance the goal of promoting healthy longevity in the human population. We, from the gathering at the Aging Research and Drug Discovery Meeting in 2023, summarised the latest developments in healthspan biotechnology, with a particular emphasis on artificial intelligence (AI), biomarkers and clocks, geroscience, and clinical trials and interventions for healthy longevity. Moreover, we provide an overview of academic research and the biotech industry focused on targeting ageing as the root of age-related diseases to combat multimorbidity and extend healthspan. We propose that the integration of generative AI, cutting-edge biological technology, and longevity medicine is essential for extending the productive and healthy human lifespan.

𝗈𝗂,ㅤ𝖽𝖺ㅤ𝗎𝗆𝖺ㅤ𝗈𝗅𝗁𝖺𝖽𝗂𝗇𝗁𝖺ㅤ𝗇𝗈ㅤ𝗆𝖾𝗎ㅤ𝗉𝖾𝗋𝖿𝗂𝗅.

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Radiotherapy is a crucial treatment option for various cancers. However, the results of radiotherapy can vary widely across different cancer types and even among patients with the same type of cancer. This variability presents a major challenge in optimizing treatment strategies and improving patient survival. Here, we collected radiotherapy phenotype and expression data from 32 TCGA cancer datasets and performed overall survival analysis for 32 cancer types. Additionally, we conducted a signaling pathway enrichment analysis to identify key pathways involved in radiotherapy resistance and sensitivity. Our findings show that radiotherapy improves survival outcomes in certain cancer types, such as glioblasoma multiforme (GBM), while worsening outcomes in others, such as low-grade glioma (LGG). Next, we focused on exploring the differences in radiotherapy outcomes between GBM and LGG, focusing on the molecular mechanisms contributing to these variations. We identify differential regulation of pathways related to programmed cell death, DNA repair, telomere maintenance, chromosome condensation, antiviral responses, and interferon signaling between GBM and LGG patients perhaps explaining radiotherapy efficacy. A genetic analysis confirmed the importance of immune response and radiotherapy outcome for LGG patients. These insights underscore the importance of personalized treatment approaches and the need for further research to improve radiotherapy outcomes in cancer patients.

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