Age-related changes of nuclear architecture in Caenorhabditis elegans.
Mutations in lamins cause premature aging syndromes in humans, including the Hutchinson-Gilford Progeria Syndrome (HGPS) and Atypical Werner Syndrome. It has been shown that HGPS cells in culture undergo age-dependent progressive changes in nuclear architecture. However, it is unknown whether similar changes in nuclear architecture occur during the normal aging process. We have observed that major changes of nuclear architecture accompany Caenorhabditis elegans aging. We found that the nuclear architecture in most nonneuronal cell types undergoes progressive and stochastic age-dependent alterations, such as changes of nuclear shape and loss of peripheral heterochromatin. Furthermore, we show that the rate of these alterations is influenced by the insulin/IGF-1 like signaling pathway and that reducing the level of lamin and lamin-associated LEM domain proteins leads to shortening of lifespan. Our work not only provides evidence for changes of nuclear architecture during the normal aging process of a multicellular organism, but also suggests that HGPS is likely a result of acceleration of the normal aging process. Because the nucleus is vital for many cellular functions, our studies raise the possibility that the nucleus is a prominent focal point for regulating aging.
Haithcock
Erin
E
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Dayani
Yaron
Y
Neufeld
Ester
E
Zahand
Adam J
AJ
Feinstein
Naomi
N
Mattout
Anna
A
Gruenbaum
Yosef
Y
Liu
Jun
J
D000375:Aging / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D015153:Blotting, Western; D017173:Caenorhabditis elegans / Q000648:ultrastructure*; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D034881:Nuclear Lamina / Q000648:ultrastructure*; D034622:RNA Interference; D015398:Signal Transduction
D007328:Insulin; D007334:Insulin-Like Growth Factor I