Ogrodnik Mikolaj
Ludwig Boltzmann Research Group Senescence and Healing of Wounds, Vienna, Austria.
Ludwig Boltzmann Institute for Experimental and Clinical Traumatology in AUVA Research Center, Vienna, Austria.
Aging Cell. 2021 Apr;20(4):e13338. doi: 10.1111/acel.13338. Epub 2021 Mar 12.
The field of research on cellular senescence experienced a rapid expansion from being primarily focused on in vitro aspects of aging to the vast territories of animal and clinical research. Cellular senescence is defined by a set of markers, many of which are present and accumulate in a gradual manner prior to senescence induction or are found outside of the context of cellular senescence. These markers are now used to measure the impact of cellular senescence on aging and disease as well as outcomes of anti-senescence interventions, many of which are at the stage of clinical trials. It is thus of primary importance to discuss their specificity as well as their role in the establishment of senescence. Here, the presence and role of senescence markers are described in cells prior to cell cycle arrest, especially in the context of replicative aging and in vivo conditions. Specifically, this review article seeks to describe the process of "cellular aging": the progression of internal changes occurring in primary cells leading to the induction of cellular senescence and culminating in cell death. Phenotypic changes associated with aging prior to senescence induction will be characterized, as well as their effect on the induction of cell senescence and the final fate of cells reviewed. Using published datasets on assessments of senescence markers in vivo, it will be described how disparities between quantifications can be explained by the concept of cellular aging. Finally, throughout the article the applicational value of broadening cellular senescence paradigm will be discussed.
细胞衰老研究领域经历了从主要关注衰老的体外方面迅速扩展到动物和临床研究的广阔领域。细胞衰老由一组标志物定义，其中许多标志物在衰老诱导之前就已存在并逐渐积累，或者在细胞衰老的背景之外被发现。这些标志物现在用于衡量细胞衰老对衰老和疾病的影响以及抗衰老干预的结果，其中许多干预正处于临床试验阶段。因此，讨论它们的特异性以及它们在衰老建立中的作用至关重要。在这里，将描述衰老标志物在细胞周期停滞之前在细胞中的存在和作用，特别是在复制性衰老和体内条件的背景下。具体而言，这篇综述文章旨在描述“细胞衰老”的过程：原代细胞中发生的内部变化的进展，导致细胞衰老的诱导并最终导致细胞死亡。将表征衰老诱导之前与衰老相关的表型变化，以及它们对细胞衰老诱导和所审查细胞最终命运的影响。利用已发表的体内衰老标志物评估数据集，将描述如何通过细胞衰老的概念来解释定量之间的差异。最后，在整篇文章中，将讨论拓宽细胞衰老范式的应用价值。
