Showing papers by "Darren J. Baker published in 2015"
TL;DR: Current progress and challenges in understanding the stressors that induce senescence in vivo, the cell types that are prone to senesce, and the autocrine and paracrine properties of senescent cells in the contexts of aging and age-related diseases as well as disease therapy are discussed.
Abstract: Cellular senescence, a process that imposes permanent proliferative arrest on cells in response to various stressors, has emerged as a potentially important contributor to aging and age-related disease, and it is an attractive target for therapeutic exploitation. A wealth of information about senescence in cultured cells has been acquired over the past half century; however, senescence in living organisms is poorly understood, largely because of technical limitations relating to the identification and characterization of senescent cells in tissues and organs. Furthermore, newly recognized beneficial signaling functions of senescence suggest that indiscriminately targeting senescent cells or modulating their secretome for anti-aging therapy may have negative consequences. Here we discuss current progress and challenges in understanding the stressors that induce senescence in vivo, the cell types that are prone to senesce, and the autocrine and paracrine properties of senescent cells in the contexts of aging and age-related diseases as well as disease therapy.
1,282 citations
TL;DR: This work focuses on the types of DNA damage found in aged stem cells, and discusses emerging mechanisms by which genomic instability may contribute to stem cell impairments and organismal aging, with particular emphasis on insights obtained from progeroid mouse models.
Abstract: Organismal aging is characterized by a progressive loss of tissue homeostasis and impaired function over time. Multi-cellular organisms activate stem and progenitor cells to replace damaged cells in order to continuously meet the functional demands of tissues. Along with tissue dysfunction, stem cell self-renewal and differentiation capacities diminish with age in concert with the accumulation of genomic damage, suggesting a potential link between genetic instability and aging. Here, we focus on the types of DNA damage found in aged stem cells, and discuss emerging mechanisms by which genomic instability may contribute to stem cell impairments and organismal aging, with particular emphasis on insights obtained from progeroid mouse models. Additionally, we discuss how age-related systemic changes may impact stem cell genomic integrity and function.
2 citations