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- W4360985414 abstract "Abstract Accumulation of senescent cells (SNCs) with a senescence‐associated secretory phenotype (SASP) has been implicated as a major source of chronic sterile inflammation leading to many age‐related pathologies. Herein, we provide evidence that a bifunctional immunotherapeutic, HCW9218, with capabilities of neutralizing TGF‐β and stimulating immune cells, can be safely administered systemically to reduce SNCs and alleviate SASP in mice. In the diabetic db/db mouse model, subcutaneous administration of HCW9218 reduced senescent islet β cells and SASP resulting in improved glucose tolerance, insulin resistance, and aging index. In naturally aged mice, subcutaneous administration of HCW9218 durably reduced the level of SNCs and SASP, leading to lower expression of pro‐inflammatory genes in peripheral organs. HCW9218 treatment also reverted the pattern of key regulatory circadian gene expression in aged mice to levels observed in young mice and impacted genes associated with metabolism and fibrosis in the liver. Single‐nucleus RNA Sequencing analysis further revealed that HCW9218 treatment differentially changed the transcriptomic landscape of hepatocyte subtypes involving metabolic, signaling, cell‐cycle, and senescence‐associated pathways in naturally aged mice. Long‐term survival studies also showed that HCW9218 treatment improved physical performance without compromising the health span of naturally aged mice. Thus, HCW9218 represents a novel immunotherapeutic approach and a clinically promising new class of senotherapeutic agents targeting cellular senescence‐associated diseases." @default.
- W4360985414 created "2023-03-30" @default.
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- W4360985414 date "2023-03-26" @default.
- W4360985414 modified "2023-10-14" @default.
- W4360985414 title "Immunotherapeutic approach to reduce senescent cells and alleviate senescence‐associated secretory phenotype in mice" @default.
- W4360985414 cites W1524549603 @default.
- W4360985414 cites W1976521197 @default.
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- W4360985414 cites W1978888457 @default.
- W4360985414 cites W2001353514 @default.
- W4360985414 cites W2007851039 @default.
- W4360985414 cites W2033885016 @default.
- W4360985414 cites W2052388837 @default.
- W4360985414 cites W2069414088 @default.
- W4360985414 cites W2070756507 @default.
- W4360985414 cites W2087404852 @default.
- W4360985414 cites W2090067193 @default.
- W4360985414 cites W2095033284 @default.
- W4360985414 cites W2111450457 @default.
- W4360985414 cites W2114785705 @default.
- W4360985414 cites W2130049617 @default.
- W4360985414 cites W2142352545 @default.
- W4360985414 cites W2147263332 @default.
- W4360985414 cites W2154903097 @default.
- W4360985414 cites W2158106881 @default.
- W4360985414 cites W2171078009 @default.
- W4360985414 cites W2171518963 @default.
- W4360985414 cites W2214536705 @default.
- W4360985414 cites W2266290735 @default.
- W4360985414 cites W2332434525 @default.
- W4360985414 cites W2401987785 @default.
- W4360985414 cites W2549447033 @default.
- W4360985414 cites W2574138833 @default.
- W4360985414 cites W2589117823 @default.
- W4360985414 cites W2605674430 @default.
- W4360985414 cites W2615498501 @default.
- W4360985414 cites W2620914886 @default.
- W4360985414 cites W2768033029 @default.
- W4360985414 cites W2773432877 @default.
- W4360985414 cites W2777786283 @default.
- W4360985414 cites W2804116873 @default.
- W4360985414 cites W2884146924 @default.
- W4360985414 cites W2884950178 @default.
- W4360985414 cites W2886713406 @default.
- W4360985414 cites W2898855247 @default.
- W4360985414 cites W2899984019 @default.
- W4360985414 cites W2906721882 @default.
- W4360985414 cites W2908922892 @default.
- W4360985414 cites W2921275786 @default.
- W4360985414 cites W2946521685 @default.
- W4360985414 cites W2947927825 @default.
- W4360985414 cites W2974643180 @default.
- W4360985414 cites W2979971613 @default.
- W4360985414 cites W2982649663 @default.
- W4360985414 cites W2988310131 @default.
- W4360985414 cites W3001036720 @default.
- W4360985414 cites W3003241421 @default.
- W4360985414 cites W3007758403 @default.
- W4360985414 cites W3008157654 @default.
- W4360985414 cites W3033290823 @default.
- W4360985414 cites W3036603151 @default.
- W4360985414 cites W3048393001 @default.