Hokkaido University · Medicine
Professor Yuki Saito's research lab focuses on the role of cellular senescence in tissue repair, fibrosis, and age-related diseases, with a particular emphasis on its dual role in promoting regeneration and contributing to chronic inflammation and fibrosis. The lab investigates how senescent cells—especially fibro-adipogenic progenitors (FAPs) and mesenchymal cells—regulate muscle and wound healing in the context of chronic myopathies and diabetes. Using preclinical models and clinical samples, the lab explores the therapeutic potential of targeting senescent cells to improve tissue repair and prevent fibrotic degeneration. Their work also extends to cancer metabolism, examining how metabolic reprogramming, such as ALDOA overexpression, drives epithelial-mesenchymal transition and tumor progression in cervical adenocarcinoma.
Figures are computed from collected data and may differ slightly.
Idiopathic inflammatory myopathies cause progressive muscle weakness and degeneration. Since high-dose glucocorticoids might not lead to full recovery of muscle function, physical exercise is also an important intervention, but some exercises exacerbate chronic inflammation and muscle fibrosis. It is unknown how physical exercise can have both beneficial and detrimental effects in chronic myopathy. Here we show that senescence of fibro-adipogenic progenitors (FAPs) in response to exercise-induce
A reliability study in which multiple raters evaluate multiple subjects was assumed in order to confirm the inter-rater reliability of rating scales. The two-way ANOVA model defining subjects and raters as random effects was applied, and the combination of the number of subjects and the number of raters that minimizes variance of the intraclass correlation coefficient (ICC) with a fixed total number of ratings (number of subjects x number of raters) was studied. The results revealed that the opt
Cellular senescence is the state in which cells undergo irreversible cell cycle arrest and acquire diverse phenotypes. It has been linked to chronic inflammation and fibrosis in various organs as well as to individual aging. Therefore, eliminating senescent cells has emerged as a potential target for extending healthy lifespans. Cellular senescence plays a beneficial role in many biological processes, including embryonic development, wound healing, and tissue regeneration, which is mediated by t
This cross-sectional study on a Japanese community-dwelling population revealed relationships between tooth loss and cognitive function. However, the interpretation of our results was hampered by a lack of data, including socioeconomic status and longitudinal observations. Future research exploring tooth loss and cognitive function is warranted.
Recent studies have revealed that metabolic reprogramming is closely associated with epithelial-mesenchymal transition (EMT) during cancer progression. Aldolase A (ALDOA) is a key glycolytic enzyme that is highly expressed in several types of cancer. In this study, we found that ALDOA is highly expressed in uterine cervical adenocarcinoma and that high ALDOA expression promotes EMT to increase malignant potentials, such as metastasis and invasiveness, in cervical adenocarcinoma cells. In human s
Pathologic diabetic wound healing is caused by sequential and progressive deterioration of hemostasis, inflammation, proliferation, and resolution/remodeling. Cellular senescence promotes wound healing; however, diabetic wounds exhibit low levels of senescent factors and accumulate senescent cells, which impair the healing process. Here we show that the number of p15<sup>INK4B</sup> + PDGFRα + senescent mesenchymal cells in adipose tissue increases transiently during early phases of wound healin
Skeletal muscle undergoes vigorous tissue remodeling after injury. However, aging, chronic inflammatory diseases, sarcopenia, and neuromuscular disorders cause muscle loss and degeneration, resulting in muscular dysfunction. Cellular senescence, a state of irreversible cell cycle arrest, acts during normal embryonic development and remodeling after tissue damage; when these processes are complete, the senescent cells are eliminated. However, the accumulation of senescent cells is a hallmark of a
Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease characterized by the involvement of multiple organs. Lupus nephritis (LN) is a major risk factor for overall morbidity and mortality in SLE patients. Hence, designing effective drugs is pivotal for treating individuals with LN. Fisetin plays a senolytic role by specifically eliminating senescent cells, inhibiting cell proliferation, and exerting anti-inflammatory, anti-oxidant, and anti-tumorigenic effects. However,
Cellular senescence is a biological mechanism that prevents abnormal cell proliferation during tissue repair, and it is often accompanied by the secretion of various factors, such as cytokines and chemokines, known as the senescence-associated secretory phenotype (SASP). SASP-mediated cell-to-cell communication promotes tissue repair, regeneration, and development. However, senescent cells can accumulate abnormally at injury sites, leading to excessive inflammation, tissue dysfunction, and intra
Neuropsychiatric manifestations targeting the central, peripheral, and autonomic nervous system are common in systemic lupus erythematosus (SLE); collectively, these symptoms are termed neuropsychiatric SLE (NPSLE). Among a wide variety of neuropsychiatric symptoms, depression is observed in about 24-39% of SLE patients. Several cytokines and chemokines have been identified as biomarkers or therapeutic targets of NPSLE; in particular, the levels of type 1 interferons, TNFs, and IL-6 are elevated
The LS-stage 2 group showed significantly different lower-limb kinematics compared with the non-LS group, including smaller peak angles of hip extension, hip flexion, and knee flexion. It would be useful to assess and improve these small peak joint angles during gait for individuals classified as LS-stage 2.
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