Dysregulation of protein posttranslational modification (PTM) can lead to a variety of pathological processes, such as abnormal sperm development, malignant tumorigenesis, depression, and aging process. SIRT7 is a NAD⁺-dependent protein deacetylase. Besides known deacetylation, SIRT7 may also have the capacity to remove other acylation. However, the roles of SIRT7-induced other deacylation in aging are still largely unknown. Here, we found that the expression of SIRT7 was significantly increased in senescent fibroblasts and aged tissues. Knockdown or overexpression of SIRT7 can inhibit or promote fibroblast senescence. Knockdown of SIRT7 led to increased pan-lysine crotonylation (Kcr) levels in senescent fibroblasts. Using modern mass spectrometry (MS) technology, we identified 5,149 Kcr sites across 1,541 proteins in senescent fibroblasts, and providing the largest crotonylome dataset to date in senescent cells. Specifically, among the identified proteins, we found SIRT7 decrotonylated PHF5A, an alternative splicing (AS) factor, at K25. Decrotonylation of PHF5A K25 contributed to decreased CDK2 expression by retained intron (RI)-induced abnormal AS, thereby accelerating fibroblast senescence, and supporting a key role of PHF5A K25 decrotonylation in aging. Collectively, our data revealed the molecular mechanism of SIRT7-induced k25 decrotonylation of PHF5A regulating aging and provide new ideas and molecular targets for drug intervention in cellular aging and the treatment of aging-related diseases, and indicating that protein crotonylation has important implications in the regulation of aging progress.

Glycosylation alterations, a key driver throughout tumorigenesis and tumor progression, could regulate the microenvironment and immune response as well as lead to harmful metabolism and cell signaling. In this study, we first comprehensively evaluated the glycosylation modification patterns of LGGs based on glycosyltransferase family genes and systematically integrated these modification patterns with tumor metabolism and immune microenvironment characteristics. Glycosylation score was also developed to quantify glycosylation modification patterns of individuals. As a result, two glycosylation modification patterns were identified, with distinct prognosis, metabolism, and immune microenvironment features. The glycosylation subtype A and cluster A were characterized by higher carbohydrates and amino acid metabolism activity, higher levels of infiltrating cells, and poor prognosis, whereas an opposite modification pattern was observed in glycosylation subtype B and cluster B. In addition, a high glycosylation score is closer to a microenvironment characterized by chronic inflammation, immunosuppression, and tumor promotion. Following analysis and validation, the glycosylation score was a reliable and independent prognostic index. More importantly, the glycosylation score influenced the response to immunotherapy, chemotherapy, or targeted therapy, which provided a novel insight into promoting personalized therapy in the future and may contribute to developing novel therapeutic drugs or exploring promising drug combination therapy strategies.