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06:23
Detection of Nuclear Blebbing and DNA Leakage in Mammalian Cells by Immunofluorescence
Published on: January 17, 2025
Longwave UV light induces the aging-associated progerin.
Hirotaka Takeuchi1, Thomas M Rünger
1Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts, USA.
The Journal of Investigative Dermatology
|February 9, 2013
Summary
Ultraviolet A (UVA) radiation accelerates skin aging by inducing progerin, a protein linked to Hutchinson-Gilford progeria syndrome (HGPS). This UVA-induced progerin accumulation causes abnormal nuclear shapes, contributing to photoaging.
Area of Science:
- Cell Biology
- Dermatology
- Genetics
Background:
- Hutchinson-Gilford progeria syndrome (HGPS) involves premature aging due to LMNA gene mutations, leading to progerin accumulation and nuclear abnormalities.
- Progerin accumulation is also observed in normal intrinsic aging, suggesting a link between HGPS and the aging process.
Purpose of the Study:
- To investigate whether UV exposure accelerates progerin accumulation and abnormal nuclear shapes, contributing to skin photoaging.
- To elucidate the mechanism by which UVA induces progerin expression and its role in photoaging.
Main Methods:
- Cultured neonatal and aged fibroblasts were exposed to UVA or UVB radiation.
- Progerin expression, nuclear morphology, and the role of oxidative damage were assessed.
- The effect of a singlet oxygen quencher (sodium azide) was evaluated.
Main Results:
- UVA, but not UVB, induced progerin expression and HGPS-like abnormal nuclear shapes in fibroblasts.
- Aged cells showed a greater response to UVA compared to neonatal cells.
- Progerin induction by UVA was mediated by oxidative damage and alternative splicing, suppressed by sodium azide.
Conclusions:
- UVA exposure accelerates intrinsic aging processes by inducing progerin accumulation and nuclear abnormalities in skin cells.
- Photoaging is partly a consequence of damage-accelerated intrinsic aging, mediated by UVA-induced oxidative stress.
- This study reveals a novel pathway contributing to skin photoaging.
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