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Lamins are rapamycin targets that impact human longevity: a study in centenarians
Giovanna Lattanzi1, Michela Ortolani, Marta Columbaro
1National Research Council of Italy, Institute of Molecular Genetics, Unit of Bologna IOR, 40136 Bologna, Italy.
Journal of Cell Science
|October 25, 2013
Summary
Prelamin A accumulates in centenarians due to reduced ZMPSTE24, impacting chromatin and 53BP1. This mechanism, targeted by rapamycin, may promote healthy human aging and longevity.
Area of Science:
- Cell Biology
- Gerontology
- Molecular Biology
Background:
- Cell nucleus organization changes with growth, development, and senescence.
- The nuclear lamina and prelamin A are implicated in cellular senescence and organism aging.
- Centenarian cells serve as a model for normal aging processes.
Purpose of the Study:
- To investigate the role of prelamin A in normal aging using cells from centenarian subjects.
- To identify mechanisms underlying healthy aging and potential therapeutic targets.
Main Methods:
- Analysis of fibroblasts from centenarian subjects.
- Assessment of nuclear envelope constituents and chromatin organization.
- Investigation of prelamin A and 53BP1 interactions.
- Rapamycin treatment of cells from younger individuals.
Main Results:
- Prelamin A accumulates in centenarian fibroblasts due to downregulated ZMPSTE24.
- Accumulated prelamin A leads to loss of heterochromatin and recruitment of inactive 53BP1.
- These effects are reproducible with rapamycin treatment in younger cells.
- Prelamin A and 53BP1 are identified as rapamycin targets linked to longevity.
Conclusions:
- Prelamin A accumulation and associated nuclear changes are linked to healthy aging in centenarians.
- Rapamycin may promote healthy aging by targeting prelamin A and 53BP1 pathways.
- These findings suggest mechanisms for adapting the nuclear environment to stress, promoting longevity.
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