In the course of TIS, cells undergo a profound epigenomic reorganization that underlies the development of a senescence-associated phenotype and formation of an inflammatory microenvironment.
Category: life extension
Glucocorticoid injection shows little benefit for knee osteoarthritis, clinical trial finds
Researchers in China have found no statistically significant advantage for infrapatellar fat pad glucocorticoid injection over saline for 12-week knee pain change or effusion synovitis volume change in inflammatory knee osteoarthritis.
Osteoarthritis affects approximately 595 million people worldwide, with knee joints identified as the most commonly affected. Symptomatic knee osteoarthritis is linked to physical disability, reduced quality of life, and increased mortality in older adults, while curative drugs remain lacking amid a rising burden tied to aging and obesity.
Some knee osteoarthritis involves inflammation, and inflammation can involve two nearby tissues—the fat pad under the kneecap and the joint lining—that are structurally interconnected and serve as important sources of inflammation in knee osteoarthritis.
This Common Blood Pressure Drug Boosts Lifespan And Slows Aging in Animals
The hypertension drug rilmenidine has been found to slow aging in worms – an effect that, if it translates to humans, could one day help us live longer and stay healthier in old age.
Rilmenidine appears to mimic the effects of caloric restriction on a cellular level, and reducing available energy while maintaining nutrition has been shown to extend lifespans in several animal models.
Whether this translates to human biology, or is a potential risk to our health, is a topic of ongoing debate. Finding ways to achieve the same benefits without the costs of extreme calorie cutting could lead to new ways to improve health in old age.
Scientists Discover Method To Erase Toxic Tau From Human Neurons
Researchers at the University of New Mexico have uncovered an unexpected role for OTULIN, an enzyme best known for its involvement in immune system regulation. The team found that OTULIN also plays a key role in the production of tau, a protein linked to many neurodegenerative disorders, along with brain inflammation and the biological processes associated with aging.
The findings were reported in the journal Genomic Psychiatry. In the study, scientists showed that disabling OTULIN stopped tau from being produced and cleared existing tau from neurons. This was achieved in two ways: by using a specially designed small molecule or by removing the gene responsible for producing the enzyme. The experiments were carried out in two types of cells, including cells derived from a person who had died from late-onset sporadic Alzheimer’s disease and human neuroblastoma cells that are commonly used in laboratory research.
Lifespan‐Extending Endogenous Metabolites
Endogenous metabolites are small molecules produced by an organism’s own metabolism. They encompass a wide range of molecules, such as amino acids, lipids, nucleotides, and sugars, which are pivotal for cellular function and organismal health (Baker and Rutter 2023). Beyond serving as biosynthetic precursors and energy substrates, many metabolites also function as dynamic modulators of signaling and gene regulatory networks by engaging in protein–metabolite interactions, allosteric regulation, and by serving as substrates for chromatin and other post-translational modifications (Boon et al. 2020 ; Hornisch and Piazza 2025). Metabolites can function as extracellular signals activating G protein-coupled receptors (GPCRs), such as free fatty acid receptors for fatty acids, GPR81 for lactate, SUCNR1 for succinate, and TGR5 for bile acids (Tonack et al. 2013). These GPCRs are expressed in gut, adipose tissue, endocrine glands, and immune cells, linking nutrient and metabolite levels to diverse physiological responses (Tonack et al. 2013). Other metabolites serve as enzyme cofactors or epigenetic regulators. For example, methyl donors like betaine provide methyl groups for DNA and histone methylation and also act as osmolytes to protect cells under stress (Lever and Slow 2010). Some metabolites even form specialized structural assemblies. For instance, guanine crystals can form structural color in feline eyes and contribute to enhanced night vision (Aizen et al. 2018).
Perturbations of endogenous metabolite levels or fluxes have been linked to genomic instability, metabolic dysfunction, and age-related diseases, motivating study of metabolites as both biomarkers and functional modulators of aging (Adav and Wang 2021 ; Tomar and Erber 2023 ; Xiao et al. 2025). Metabolomic studies reveal characteristic metabolite changes in diabetes, cardiovascular disease, and Alzheimer’s disease (AD) (Panyard et al. 2022), suggesting that metabolites not only reflect organismal state but also can actively influence aging pathways. In subsequent sections, we will examine specific endogenous metabolites implicated in longevity regulation.
Age-independent and targetable transcription factor networks regulating CD8+ T cell senescence in aging humans
Turano et al. reveal the transcription factor networks driving CD8+ T cell senescence in healthy aging humans. Inhibiting key transcription factors modulates the senescence program and partially restores responsiveness to TCR stimulation. They also show that CD8+ T cell senescence gene signatures predict response to CAR-T cell therapy in B cell lymphomas.
Tissue repair slows in old age. These proteins speed it back up
As we age, we don’t recover from injury or illness like we did when we were young. But new research from UCSF has found gene regulators—proteins that turn genes on and off—that could restore the aging body’s ability to self-repair.
The scientists looked at fibroblasts, which build the scaffolding between cells that give shape and structure to our organs.
Fibroblasts maintain this scaffolding in the face of normal wear, disease, and injury. But over time, they slow down, and the body suffers.
Programmable Macrophage Mimics for Inflammatory Meniscus Regeneration via Nanotherapy
JUST PUBLISHED: programmable macrophage mimics for inflammatory meniscus regeneration via nanotherapy
Click here to read the latest free, Open Access Article from Research.
The meniscus is a fibrocartilaginous tissue and organ in the human knee joint that serves critical functions, including load transmission, shock absorption, joint stability, and lubrication. Meniscal injuries are among the most common knee injuries, typically caused by acute trauma or age-related degeneration [1– 3]. Minor meniscal injuries are usually treated with in situ arthroscopic procedures or conservative methods, whereas larger or more severe injuries often necessitate total meniscus replacement. Recent advances in materials science and manufacturing techniques have enabled transformative tissue-engineering strategies for meniscal therapy [4, 5]. Several stem cell types, including synovium-derived mesenchymal stem cells, bone-marrow-derived mesenchymal stem cells, and adipose-derived stem cells (ADSCs), have been investigated as candidate seed cells for meniscal regeneration and repair. Notably, ADSCs are clinically promising because of their ease of harvest, high inducibility, innate anti-inflammatory properties, and potential to promote fibrocartilage regeneration [6– 8]. Our group has developed a series of decellularized matrix scaffolds for auricular, nasal, tracheal, and articular cartilage repair using 3-dimensional (3D) bioprinting techniques, successfully repairing meniscus defects and restoring physiological function [9– 12]. However, current tissue-engineering strategies for meniscus defect repair commonly rely on a favorable regenerative microenvironment. Pathological conditions such as osteoarthritis (OA) [13 – 16], the most prevalent joint disorder, often create inflammatory environments that severely hinder meniscus regeneration [17 – 21]. Moreover, meniscal injury exacerbates the local inflammatory milieu, further impeding tissue healing and inevitably accelerating OA progression. Therefore, there is an urgent need to establish a cartilaginous immune microenvironment that first mitigates early-stage inflammation after meniscal injury and then sequentially promotes later-stage fibrocartilage regeneration [22 – 25].
Currently, targeted regulation using small-molecule drug injections is commonly employed to treat inflammatory conditions in sports medicine [26,27]. Most of these drugs exhibit broad-spectrum anti-inflammatory effects and inevitably cause varying degrees of side effects by activating nonspecific signaling pathways. Polyethyleneimine is a highly cationic polymer. It is widely used to modulate inflammation by adsorbing and removing negatively charged proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), via electrostatic interactions [28–31]. Notably, modifying polyethyleneimine into its branched form (branched polyethyleneimine [BPEI]) has been shown to improve cytocompatibility and enhance in vivo metabolic cycling.