Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
National Institute of Biological Sciences (NIBS), Beijing 102206, China.
G3 (Bethesda). 2023 Apr 11;13(4). doi: 10.1093/g3journal/jkad029.
Abnormal nuclear morphology is suggested to be a hallmark of aging and one such abnormality is nuclear blebbing. However, little is known about whether and how nuclear blebbing participates in animal aging, and what regulates it. In this study, we show that the frequency of nuclear blebbing in the hypodermis increases during aging in wild-type C. elegans. These nuclear blebs are enveloped by the nuclear lamina, the inner and the outer nuclear membrane, and 42% of them contain chromatin. Although nuclear blebbing could lead to DNA loss if chromatin-containing blebs detach and fuse with lysosomes, we find by time-lapse imaging that nuclear blebs rarely detach, and the estimated lifetime of a nuclear bleb is 772 h or 32 days. The amount of DNA lost through nuclear blebbing is estimated to be about 0.1% of the total DNA loss by adult Day 11. Furthermore, the frequency of nuclear blebbing does not correlate with the rate of aging in C. elegans. Old age does not necessarily induce nuclear blebbing, neither does starvation, heat stress, or oxidative stress. Intriguingly, we find that proliferation of germ cells promotes nuclear blebbing.
异常的核形态被认为是衰老的标志之一,其中一种异常是核泡化。然而,人们对于核泡化是否以及如何参与动物衰老,以及是什么调节了它知之甚少。在这项研究中,我们表明,在野生型秀丽隐杆线虫的皮下组织中,核泡化的频率随着衰老而增加。这些核泡被核纤层、内、外核膜所包裹,其中 42%的核泡含有染色质。尽管含有染色质的核泡如果脱离并与溶酶体融合可能导致 DNA 丢失,但我们通过延时成像发现,核泡很少脱离,并且一个核泡的估计寿命为 772 小时或 32 天。通过核泡化丢失的 DNA 量估计约占成年第 11 天总 DNA 丢失量的 0.1%。此外,核泡化的频率与秀丽隐杆线虫的衰老速度无关。衰老不一定会诱导核泡化,饥饿、热应激或氧化应激也不会。有趣的是,我们发现生殖细胞的增殖促进了核泡化。