Sirtuins, initially described as histone deacetylases and gene silencers in yeast, are now known to have many more functions and to be much more abundant in living organisms. The increasing evidence of sirtuins in the field of ageing and age-related diseases indicates that they may provide novel targets for treating diseases associated with aging and perhaps extend human lifespan. Here, we summarize some of the recent discoveries in sirtuin biology that clearly implicate the functions of sirtuins in the regulation of aging and age-related diseases. Furthermore, human sirtuins are considered promising therapeutic targets for anti-aging and ageing-related diseases and have attracted interest in scientific communities to develop small molecule activators or drugs to ameliorate a wide range of ageing disorders. In this review, we also summarize the discovery and development status of sirtuin-targeted drug and further discuss the potential medical strategies of sirtuins in delaying aging and treating age-related diseases.

Osteoarthritis (OA) is a progressive joint disease characterized by inflammation and cartilage destruction, and its progression is closely related to imbalances in the M1/M2 synovial macrophages. A two‐pronged strategy for the regulation of intracellular/extracellular nitric oxide (NO) and hydrogen protons for reprogramming M1/M2 synovial macrophages is proposed. The combination of carbonic anhydrase IX (CA9) siRNA and NO scavenger in “two‐in‐one” nanocarriers (NAHA‐CaP/siRNA nanoparticles) is developed for progressive OA therapy by scavenging NO and inhibiting CA9 expression in synovial macrophages. In vitro experiments demonstrate that these NPs can significantly scavenge intracellular NO similar to the levels as those in the normal group and downregulate the expression levels of CA9 mRNA (≈90%), thereby repolarizing the M1 macrophages into the M2 phenotype and increasing the expression levels of pro‐chondrogenic TGF‐β1 mRNA (≈1.3‐fold), and inhibiting chondrocyte apoptosis. Furthermore, in vivo experiments show that the NPs have great anti‐inflammation, cartilage protection and repair effects, thereby effectively alleviating OA progression in both monoiodoacetic acid‐induced early and late OA mouse models and a surgical destabilization of medial meniscus‐induced OA rat model. Therefore, the siCA9 and NO scavenger “two‐in‐one” delivery system is a potential and efficient strategy for progressive OA treatment.

The meniscus is a fibrocartilaginous tissue of the knee joint that plays an important role in load transmission, shock absorption, joint stability maintenance, and contact stress reduction. Mild meniscal injuries can be treated with simple sutures, whereas severe injuries inevitably require meniscectomy. Meniscectomy destroys the mechanical microenvironment of the knee joint, leading to cartilage degeneration and osteoarthritis. Tissue engineering techniques, as a strategy with diverse sources and customizable and adjustable mechanical and biological properties, have emerged as promising approaches for the treatment of meniscal injuries and are represented by 3D printing. Notably, the heterogeneity of the meniscus, including its anatomical structure, cell phenotype, extracellular matrix, and biomechanical properties, is crucial for its normal function. Therefore, the construction of heterogeneous tissue-engineered menisci (TEM) has become a research hotspot in this field. In this review, we systematically summarize the heterogeneity of menisci and 3D-printed strategies for tissue-engineered anisotropic menisci. The manufacturing techniques, biomaterial combinations, surface functionalization, growth factors, and bioreactors related to 3D-printed strategies are introduced and a promising direction for the future research is proposed.

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Editorial on the Research Topic Bio engineering and translational research for b one and joint diseasesMusculoskeletal disorders, commonly caused by sporting injuries, aging, accidents, and pathological factors, are one of the nonnegligible burdens that render severe pain and disability (Shang et al., 2022). As a long-term and costing disease, osteoarthritis occurs at a six folds higher rate, secondary to joint and bone lesions such as ligament rupture, cartilage defects, meniscus tear, and bone injuries (Snoeker et al., 2020). Different tissues show a great variation in the ability of post-injury self-repair. Due to increased angiogenesis and the capability to differentiate osteoblasts (Glowacki, 1998), bone is recognized as relatively prone to heal when lesions are small, whereas large instances remain challenging clinically and preclinically (Schemitsch, 2017). Unlike the adequation of blood supply in bone tissue, articular cartilage is an avascular, alymphatic, aneural, and hypocellular structure (Pathria et al., 2016). Chondrocytes, the predominant and welldifferentiated type of cells in cartilage, cluster in the lacuna rich in water, proteoglycans, and collagens. Under natural situations, articular cartilage microstructure degenerates in pace with systemic aging, such as a loss in water volume and thinning of the calcified cartilage layer (Hoemann et al., 2012). Due to its biological properties, once injured, cartilage can hardly heal itself, rather injury progresses to the deeper layers and is finally in need of arthroplasty (Baumann et al., 2019). Current strategies, including conservative surgeries like arthroscopic debridement and chondroplasty (Chilelli et al., 2017), bone marrow stimulating therapy like microfracture (Allahabadi et al., 2021), and autologous transfer therapy such as osteochondral autograft transfer (McCormick et al., 2014) cated on the tibia plateau, are indispensable structures that facilitate load transmission, shock absorption, joint lubrication, and proprioception (Fox et al., 2015). Meniscus tears, commonly due to trauma or degenerative diseases, badly influence the mobility of knees, especially in athletes (Fox et al., 2015). With adequate vascularity only in the outer red-red zone, tears occurring in the inner white-white zone cannot self-repair (Makris et al., 2011). Tendon and ligament injuries are also health problems that cause pain and instability of