Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
Aging (Albany NY). 2020 Dec 22;12(24):24481-24483. doi: 10.18632/aging.202321.
Progeroid murine models represent an emerging tool to investigate mechanisms of aging in an expedient and efficient manner. One prominent mechanism of aging is the accumulation of DNA damage and subsequent increase in cellular senescence, leading to age related pathologies. hypomorphic mice, which have a reduced level of the ERCC1-XPF DNA repair endonuclease complex, accumulate spontaneously occurring endogenous DNA damage similar to naturally aged mice, but at a faster rate. The resulting genomic damage gives rise to a senescent cell burden that is comparable to that of a naturally aged mouse. In fact, the expression of senescence and senescence-associated secretory phenotype (SASP) markers in 4-5-month-old mice, along with other measurements of senescence, were equivalent and never exceeded the extent of that found in naturally aged mice. Furthermore, many features of both natural murine aging and human aging are present in mice. An emerging use of these mice is the ability to study age-related signaling pathways, including identifying different types of senescent cells and their key senescent cell anti-apoptotic pathways (SCAPs). Most importantly, this model represents a rapid, cost-effective mouse model for the evaluation of senolytic drugs and other gerotherapeutics.
早衰症小鼠模型是一种新兴的工具，可用于快速有效地研究衰老机制。衰老的一个突出机制是 DNA 损伤的积累和随后的细胞衰老增加，导致与年龄相关的病理。ERCC1-XPF DNA 修复内切酶复合物水平降低的功能获得性突变小鼠会自发积累内源性 DNA 损伤，类似于自然衰老的小鼠，但速度更快。由此产生的基因组损伤导致衰老细胞负担与自然衰老小鼠相当。事实上，4-5 个月大的 小鼠中衰老和衰老相关分泌表型 (SASP) 标志物的表达，以及其他衰老测量指标，与自然衰老小鼠相当，从未超过自然衰老小鼠的程度。此外，许多自然发生的小鼠衰老和人类衰老的特征都存在于 小鼠中。这些小鼠的一个新用途是研究与年龄相关的信号通路，包括鉴定不同类型的衰老细胞及其关键的衰老细胞抗凋亡途径 (SCAPs)。最重要的是，这种模型代表了一种快速、具有成本效益的小鼠模型，可用于评估衰老细胞溶解药物和其他衰老治疗药物。
