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Uncoupling of mTORC1 from E2F activity maintains DNA damage and senescence

10 months 4 weeks ago
DNA damage is a primary trigger for cellular senescence, which in turn causes organismal aging and is a promising target of anti-aging therapies. Most DNA damage occurs when DNA is fragile during DNA replication in S phase, but senescent cells maintain DNA damage long-after DNA replication has stopped. How senescent cells induce DNA damage and why senescent cells fail to repair damaged DNA remain open questions. Here, we combine reversible expression of the senescence-inducing CDK4/6 inhibitory...
Leighton H Daigh

The role of the dynamic epigenetic landscape in senescence: orchestrating SASP expression

10 months 4 weeks ago
Senescence and epigenetic alterations stand out as two well-characterized hallmarks of aging. When cells become senescent, they cease proliferation and release inflammatory molecules collectively termed the Senescence-Associated Secretory Phenotype (SASP). Senescence and SASP are implicated in numerous age-related diseases. Senescent cell nuclei undergo epigenetic reprogramming, which intricately regulates SASP expression. This review outlines the current understanding of how senescent cells...
Nirmalya Dasgupta

Cyclophilin D plays a critical role in the survival of senescent cells

10 months 4 weeks ago
Senescent cells play a causative role in many diseases, and their elimination is a promising therapeutic strategy. Here, through a genome-wide CRISPR/Cas9 screen, we identify the gene PPIF, encoding the mitochondrial protein cyclophilin D (CypD), as a novel senolytic target. Cyclophilin D promotes the transient opening of the mitochondrial permeability transition pore (mPTP), which serves as a failsafe mechanism for calcium efflux. We show that senescent cells exhibit a high frequency of...
Margherita Protasoni

The landscape of RNA binding proteins in mammalian spermatogenesis

10 months 4 weeks ago
Science, Volume 386, Issue 6720, October 2024.
Yang Li, Yuanyuan Wang, Yue-Qiu Tan, Qiuling Yue, Yueshuai Guo, Ruoyu Yan, Lanlan Meng, Huicong Zhai, Lingxiu Tong, Zihan Yuan, Wu Li, Cuicui Wang, Shenglin Han, Sen Ren, Yitong Yan, Weixu Wang, Lei Gao, Chen Tan, Tongyao Hu, Hao Zhang, Liya Liu, Pinglan…