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Heterochronic parabiosis regulates the extent of cellular senescence in multiple tissues.
GeroScience ( IF 5.3 ) Pub Date : 2020-04-13 , DOI: 10.1007/s11357-020-00185-1
Matthew J Yousefzadeh 1, 2, 3 , John E Wilkinson 4 , Brian Hughes 1, 2 , Namrata Gadela 3 , Warren C Ladiges 4 , Nam Vo 5 , Laura J Niedernhofer 1, 2, 3 , Derek M Huffman 6 , Paul D Robbins 1, 2, 3
Affiliation  

An increase in the burden of senescent cells in tissues with age contributes to driving aging and the onset of age-related diseases. Genetic and pharmacologic elimination of senescent cells extends both health span and life span in mouse models. Heterochronic parabiosis in mice has been used to identify bloodborne, circulating pro- and anti-geronic factors able to drive or slow aging, respectively. However, whether factors in the circulation also regulate senescence is unknown. Here, we measured the expression of senescence and senescence-associated secretory phenotype (SASP) markers in multiple tissues from 4- to 18-month-old male mice that were either isochronically or heterochronically paired for 2 months. In heterochronic parabionts, the age-dependent increase in senescence and SASP marker expression was reduced in old mice exposed to a young environment, while senescence markers were concurrently increased in young heterochronic parabionts. These findings were supported by geropathology analysis using the Geropathology Grading Platform that showed a trend toward reduced hepatic lesions in old heterochronic parabionts. In summary, these results demonstrate that senescence is regulated in part by circulating geronic factors and suggest that one of the possible mediators of the rejuvenating effects with heterochronic parabiosis is through the reduction of the senescent cell burden.

中文翻译:

异时生物共生调节多种组织中细胞衰老的程度。

随着年龄的增长,组织中衰老细胞的负担增加导致衰老和与年龄有关的疾病的发作。遗传性和药理性消除衰老细胞可延长小鼠模型的健康寿命和寿命。小鼠异时共生已被用于鉴定能够分别驱动或减缓衰老的血液传播,循环的促衰老和抗衰老因子。但是,尚不清楚循环中的因素是否也调节衰老。在这里,我们测量了4至18个月大的雄性小鼠的多个组织中等时或异时配对2个月的衰老和衰老相关的分泌表型(SASP)标记的表达。在异时生物中,暴露于年轻环境的老年小鼠的衰老和SASP标记表达随年龄的增加而降低,而年轻异时生物的衰老标记则同时升高。这些发现得到了使用Geropathology分级平台进行的Geropathology分析的支持,该平台显示出在老年异时性抛物型生物中肝病灶减少的趋势。总而言之,这些结果表明,衰老部分受循环中的衰老因子调控,并表明异时共生的复兴作用的可能介质之一是通过减少衰老细胞负担。这些发现得到了使用Geropathology分级平台进行的Geropathology分析的支持,该平台显示出在老年异时性抛物型生物中肝病灶减少的趋势。总而言之,这些结果表明,衰老部分受循环中的衰老因子调控,并表明异时共生的复兴作用的可能介质之一是通过减少衰老细胞负担。这些发现得到了使用Geropathology分级平台进行的Geropathology分析的支持,该平台显示出在老年异时性抛物型生物中肝病灶减少的趋势。总而言之,这些结果表明,衰老部分受循环中的衰老因子调控,并表明异时共生的复兴作用的可能介质之一是通过减少衰老细胞负担。
更新日期:2020-04-13
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