Inflammaging and immunosenescence-driven remodeling of the immune microenvironment in osteoarthritis: mechanisms, immune regulation and immune reprogramming
Aug 2026· Frontiers in Immunology· 0 citations· 141 references
TL;DR
It is highlighted that future OA treatment may gradually shift from symptom-oriented management toward disease-modifying therapy based on the identification of immune endotypes, and further studies are required to validate the underlying molecular mechanisms, evaluate safety, and conduct clinical trials, thereby facilitating the clinical translation of immune reprogramming strategies for OA.
Abstract
Osteoarthritis (OA) is a disorder of the whole-joint microenvironment involving mechanical loading, aging, metabolic stress, and dysregulated immune homeostasis. Within the OA joint microenvironment, senescent chondrocytes, synovial fibroblasts, and diverse immune cell populations contribute to a persistently amplified inflammatory network through the senescence-associated secretory phenotype (SASP), damage-associated molecular patterns (DAMPs), and signaling pathways mediated by metabolic reprogramming. In this context, inflammaging and immunosenescence are considered key mechanistic axes linking aging, chronic low-grade inflammation, cartilage matrix degradation, synovial inflammation, and subchondral bone remodeling, thereby playing central roles in OA pathogenesis. As a narrative review, this article aims to provide an integrated analysis of the cellular basis, molecular mechanisms, joint immune microenvironment, biomarkers, and immune reprogramming strategies related to inflammaging and immunosenescence in OA. Particular emphasis is placed on macrophage polarization, senescent cell clearance, SASP inhibition, and gene-editing approaches. This review highlights that future OA treatment may gradually shift from symptom-oriented management toward disease-modifying therapy based on the identification of immune endotypes. Nevertheless, further studies are required to validate the underlying molecular mechanisms, evaluate safety, and conduct clinical trials, thereby facilitating the clinical translation of immune reprogramming strategies for OA.
It is argued that formation of a tumour-intrinsic niche is a prerequisite for BRAF-mutant CRC seeding to distant organs and that interference with niche formation may help avoid metastatic relapse.
J. Bugter, L. El Bouazzaoui, E. Küçükköse et al.· bioRxiv· 2 citations
It is concluded that bridging the gap between foundational CRISPR research and its real-world applications is imperative and future efforts should focus on democratizing tools via open-source platforms, advancing delivery systems, and fostering sustainable innovation through synthetic biology integration to fully realize the transformative potential of genome editing in organisms beyond model organisms.
S. Sarsaiya, Archana Jain, Jishuang Chen et al.· Biotechnology Advances· 2 citations
Global agriculture faces a 2050 "perfect storm": rising temperatures, elevated CO2, and compound climate stresses – heatwaves, flash droughts, and floods – that cause non-linear yield losses. The Green revolution paradigm of maximizing yield potential (Yp) is no longer sufficient. We argue that the primary breeding target must shift decisively to yield stability (Ys): consistent performance across volatile and non-analog environments. Unlike prior trait-focused reviews that catalog physiological mechanisms without breeder-ready deployment tools, here we provide a breeder-ready roadmap of 20 keystone physiological traits, each with its genetic target, validated marker, donor germplasm, heritability, yield penalty, and deployment timeline. Traits such as SUB1A (submergence), HKT1;5 (salt exclusion), and DRO1 (deep rooting) are ready for immediate marker-assisted introgression. We highlight that the time and cost for modern breeding methods are reducing i.e., marker-assisted backcrossing (2–3 years; $1.50–$5.00 per marker), genomic selection (3–5 years; $15–$40 per sample), and speed breeding (reducing cycles by up to 60%). Critically, the regulatory landscape is diverging while the United States maintains a streamlined, notification-only process for transgene-free edits, the European Union has recently adopted a new framework (April 2026) that classifies gene-edited plants into two categories, aiming to reduce the historic $15M+ barrier for category-1 equivalents. This roadmap is distinctive in its direct translation of 100 physiological traits into 20 deployable keystone targets, with explicit genetic resources, cost timelines, and regulatory pathways, making it an actionable plan rather than a theoretical framework. We conclude with time-bound milestones: universal genotyping for all MAS-ready traits by 2030, harmonization of global regulatory pathways by 2035, and broad-scale genomic prediction deployment by 2040. The roadmap is not merely a beginning; it is an actionable plan for global food security.
M. A. Nawaz, K. Golokhvast· Integrative Plant Biotechnol...· 0 citations
The exogenous addition of xylose as a signal to initiate genetic editing achieved the spatiotemporal regulation of the target gene-activating gene editing that restricts growth only after the completion of the strain's growth phase, and raised the total pigment yield.
Jiawen Du, Long-Xiang Liu, Jiawen Gao et al.· Bioresource Technology· 0 citations
This review summarizes the trajectory of iPSC reprogramming technologies and identifies the core “translational triltrilas”, namely, the inherent tradeoffs between security, homogeneity, and scalability, and proposes a comprehensive strategy to overcome these bottlenecks.
Mengmeng Chen, Ning Zuo, Qi Wang et al.· Frontiers in Cell and Develo...· 0 citations
A new method for surgically removing training examples from a model reveals that as datasets grow, the link between what a model learns and what it produces dissolves.
MIT News · Artificial Intelligence· news.mit.eduAug 17, 2026
