Department of Genetics, Harvard Medical School, Boston, United States.
Department of Orthopedics, Boston Children's Hospital, Boston, United States.
Elife. 2020 Jan 27;9:e50523. doi: 10.7554/eLife.50523.
The use of genetics has been invaluable in defining the complex mechanisms of aging and longevity. Zebrafish, while a prominent model for vertebrate development, have not been used systematically to address questions of how and why we age. In a mutagenesis screen focusing on late developmental phenotypes, we identified a new mutant that displays aging phenotypes at young adult stages. We find that the phenotypes are due to loss-of-function in the non-classical cadherin . The premature aging is not associated with increased cellular senescence or telomere length but is a result of a failure to maintain progenitor cell populations. We show that is essential for maintenance of stem cell progenitors in late stages. Caloric restriction can ameliorate aging phenotypes. These data suggest that function helps to mediate stem cell maintenance during maturation and homeostasis of tissues and thus regulates the onset or expressivity of aging phenotypes.
遗传学在阐明衰老和长寿的复杂机制方面发挥了巨大的作用。斑马鱼虽然是脊椎动物发育的重要模式生物，但尚未被系统地用于研究衰老的原因和机制。在一项针对晚期发育表型的诱变筛选中，我们发现了一个新的突变体，它在成年早期就表现出衰老表型。我们发现这些表型是由于非经典钙黏蛋白的功能丧失所致。这种早衰与细胞衰老或端粒长度的增加无关，而是由于祖细胞群体无法维持所致。我们表明，在晚期阶段，对于维持干细胞祖细胞是必需的。限制热量摄入可以改善的衰老表型。这些数据表明，功能有助于在组织的成熟和稳态过程中调节干细胞的维持，从而调控衰老表型的发生或表现度。
