Sex-specific preservation of neuromuscular function and metabolism following systemic transplantation of multipotent adult stem cells in a murine model of progeria.
Sex-specific preservation of neuromuscular function and metabolism following systemic transplantation of multipotent adult stem cells in a murine model of progeria.
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DOI：
10.1007/s11357-023-00892-5
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发表时间：
2024-02
期刊：
影响因子：
5.6
通讯作者：
Lavasani, Mitra
中科院分区：
文献类型：
--
作者：
Thompson, Seth D. D.;Barrett, Kelsey L. L.;Rugel, Chelsea L. L.;Redmond, Robin;Rudofski, Alexia;Kurian, Jacob;Curtin, Jodi L. L.;Dayanidhi, Sudarshan;Lavasani, Mitra
关键词：
骨质疏松症是一种以肌肉质量和功能随年龄增长而丧失为特征的疾病，其发病和发病率在性别之间存在很大差异。目前，还没有临床干预措施成功阻止与年龄相关的肌肉损伤，因为这种下降往往是多因素的。此前，我们发现，系统移植我们独特的成年多潜能肌源性干细胞/祖细胞(MDSPC)-从幼鼠中分离出来-但不是老年-延长了DNA损伤的早衰症小鼠模型的健康跨度，早衰症是一种加速衰老的疾病。此外，在肌肉和大脑中诱导新生血管-在那里没有检测到移植细胞-强烈表明了一种系统性治疗机制，可能是通过循环分泌因子激活的。在这里，我们使用ZMPSTE24缺陷小鼠，一个层蛋白A缺陷的早衰症模型，来研究年轻的MDSPC保存神经肌肉组织结构和功能的能力。我们发现孕激素ZMPST24缺陷小鼠忠实地表现出骨质疏松症和年龄相关的代谢功能障碍。然而，将年轻的MDSPC系统移植到ZMPSTE24缺乏孕激素的小鼠体内，以性别特异性的方式在其6个月的生命周期中维持肌肉组织的健康功能和组织病理学。事实上，系统移植了年轻的MDSPC的雌性-而不是雄性-小鼠表现出显著的肌肉耐力、肌肉纤维大小、线粒体呼吸测量和神经肌肉连接形态计量学的保存。这些新的发现有力地表明，年轻的MDSPC通过分泌再生因子来调节老年动物的系统环境，以性别特有的方式维持健康的动态平衡，并且女性肌肉微环境在老年时仍然对外源再生线索做出反应。这项工作突出了神经肌肉组织退化中与年龄和性别相关的差异，以及通过系统再生治疗保护老年人健康的未来前景。网上版载有补充材料，可在10.1007/s11357.023-00892-5查阅。
Onset and rates of sarcopenia, a disease characterized by a loss of muscle mass and function with age, vary greatly between sexes. Currently, no clinical interventions successfully arrest age-related muscle impairments since the decline is frequently multifactorial. Previously, we found that systemic transplantation of our unique adult multipotent muscle-derived stem/progenitor cells (MDSPCs) isolated from young mice—but not old—extends the health-span in DNA damage mouse models of progeria, a disease of accelerated aging. Additionally, induced neovascularization in the muscles and brain—where no transplanted cells were detected—strongly suggests a systemic therapeutic mechanism, possibly activated through circulating secreted factors. Herein, we used ZMPSTE24-deficient mice, a lamin A defect progeria model, to investigate the ability of young MDSPCs to preserve neuromuscular tissue structure and function. We show that progeroid ZMPST24-deficient mice faithfully exhibit sarcopenia and age-related metabolic dysfunction. However, systemic transplantation of young MDSPCs into ZMPSTE24-deficient progeroid mice sustained healthy function and histopathology of muscular tissues throughout their 6-month life span in a sex-specific manner. Indeed, female—but not male—mice systemically transplanted with young MDSPCs demonstrated significant preservation of muscle endurance, muscle fiber size, mitochondrial respirometry, and neuromuscular junction morphometrics. These novel findings strongly suggest that young MDSPCs modulate the systemic environment of aged animals by secreted rejuvenating factors to maintain a healthy homeostasis in a sex-specific manner and that the female muscle microenvironment remains responsive to exogenous regenerative cues in older age. This work highlights the age- and sex-related differences in neuromuscular tissue degeneration and the future prospect of preserving health in older adults with systemic regenerative treatments. The online version contains supplementary material available at 10.1007/s11357-023-00892-5.
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影响因子：
8.1
作者：
Englund, Davis A.;Jolliffe, Alyssa;Aversa, Zaira;Zhang, Xu;Sturmlechner, Ines;Sakamoto, Ayumi E.;Zeidler, Julianna D.;Warner, Gina M.;McNinch, Colton;White, Thomas A.;Chini, Eduardo N.;Baker, Darren J.;van Deursen, Jan M.;LeBrasseur, Nathan K.
通讯作者：
LeBrasseur, Nathan K.
影响因子：
3.7
作者：
Bloemberg D;Quadrilatero J
通讯作者：
Quadrilatero J
DOI：
10.1073/pnas.192460799
发表时间：
2002-10-01
影响因子：
11.1
作者：
Bergo, MO;Gavino, B;Young, SG
通讯作者：
Young, SG
DOI：
10.1159/000319997
发表时间：
2010-01-01
期刊：
BODY COMPOSITION AND AGING
影响因子：
--
作者：
Berger, Michael J.;Doherty, Timothy J.
通讯作者：
Doherty, Timothy J.
影响因子：
64.8
作者：
Conboy, IM;Conboy, MJ;Rando, TA
通讯作者：
Rando, TA