4.4 Article

Nucleophagy delays aging and preserves germline immortality

期刊

NATURE AGING
卷 3, 期 1, 页码 34-+

出版社

SPRINGERNATURE
DOI: 10.1038/s43587-022-00327-4

关键词

-

向作者/读者索取更多资源

The degradation of nuclear components mediated by ANC-1 and its counterparts nesprin-1 and nesprin-2 plays a crucial role in limiting nucleolar size and function, and is involved in soma longevity and germline immortality mechanisms. Autophagy of nuclear proteins is important for fertility and aging, and impairment of nucleophagy can diminish stress resistance, germline immortality, and longevity.
Nuclear morphology changes with aging, but the role of these changes and the underlying mechanisms are not fully understood. The authors find that the nuclear envelope anchor protein ANC-1 in worms, and its counterpart nesprin-1 and nesprin-2 in mammals, promotes the degradation of nuclear components to limit nucleolar size and function in a soma longevity and germline immortality mechanism. Marked alterations in nuclear ultrastructure are a universal hallmark of aging, progeroid syndromes and other age-related pathologies. Here we show that autophagy of nuclear proteins is an important determinant of fertility and aging. Impairment of nucleophagy diminishes stress resistance, germline immortality and longevity. We found that the nematode Caenorhabditis elegans nuclear envelope anchor protein, nuclear anchorage protein 1 (ANC-1) and its mammalian ortholog nesprin-2 are cleared out by autophagy and restrict nucleolar size, a biomarker of aging. We further uncovered a germline immortality assurance mechanism, which involves nucleolar degradation at the most proximal oocyte by ANC-1 and key autophagic components. Perturbation of this clearance pathway causes tumor-like structures in C. elegans, and genetic ablation of nesprin-2 causes ovarian carcinomas in mice. Thus, autophagic recycling of nuclear components is a conserved soma longevity and germline immortality mechanism that promotes youthfulness and delays aging under conditions of stress.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.4
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据