Impact of Mlkl or Ripk3 deletion on age-associated liver inflammation, metabolic health, and lifespan.

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Tác giả: Nagib Ahsan, Shylesh Bhaskaran, Sathyaseelan S Deepa, Chao Jiang, Sabira Mohammed, Evan Nicklas, Phoebe Ohene-Marfo, Zongkai Peng, Ramasamy Selvarani, Amit Singh, Nidheesh Thadathil, Albert Tran, Dawei Wang, Zhibo Yang

Ngôn ngữ: eng

Ký hiệu phân loại: 271.6 *Passionists and Redemptorists

Thông tin xuất bản: Switzerland : GeroScience , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 50235

Chronic, low-grade inflammation is a hallmark of aging and various age-related diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD). The prevalence of metabolic dysfunction-associated steatohepatitis (MASH), an advanced form of MASLD, increases with age and contributes to morbidity and mortality among the elderly. This study investigates the role of necroptosis, a programmed cell death pathway that promotes inflammation, in liver inflammaging and age-associated MASLD by utilizing genetic ablation models of two key necroptosis proteins, Mlkl or Ripk3. The absence of Mlkl or Ripk3 significantly reduced liver inflammation, steatosis, and fibrosis in aged male mice, supporting the role of necroptosis in age-associated MASLD. Additionally, Mlkl or Ripk3 deletion impacted other non-necroptotic cellular processes that drive inflammation and MASLD, such as cellular senescence, apoptosis, and autophagy in aged liver. Levels of plasma TNFα and IL6, key proinflammatory cytokines associated with inflammaging, are reduced in Mlkl
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