Nuclear lamina defects cause ATM-dependent NF-?B activation and link accelerated aging to a systemic inflammatory response
Language: 
English
Abstract: 

Alterations in the architecture and dynamics of the nuclear lamina have a causal role in normal and accelerated aging through both cell-autonomous and systemic mechanisms. However, the precise nature of the molecular cues involved in this process remains incompletely defined. Here we report that the accumulation of prelamin A isoforms at the nuclear lamina triggers an ATM- and NEMO-dependent signaling pathway that leads to NF-?B activation and secretion of high levels of proinflammatory cytokines in two different mouse models of accelerated aging (Zmpste24(-/-) and Lmna(G609G/G609G) mice). Causal involvement of NF-?B in accelerated aging was demonstrated by the fact that both genetic and pharmacological inhibition of NF-?B signaling prevents age-associated features in these animal models, significantly extending their longevity. Our findings provide in vivo proof of principle for the feasibility of pharmacological modulation of the NF-?B pathway to slow down the progression of physiological and pathological aging.

Author(s): 
Osorio, Fernando G.
B·rcena, Clea
Soria-Valles, Clara
Ramsay, Andrew J.
de Carlos, FÈlix
Cobo, Juan
Fueyo, Antonio
Freije, JosÈ M. P.
LÛpez-OtÌn, Carlos
Item Type: 
Journal Article
Publication Title: 
Genes & Development
Journal Abbreviation: 
Genes Dev.
Publication Date: 
10/15/2012
Publication Year: 
2012
Pages: 
2311-2324
Volume: 
26
Issue: 
20
ISSN: 
1549-5477
DOI: 
10.1101/gad.197954.112
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 23019125 PMCID: PMC3475803

Turabian/Chicago Citation

Fernando G. Osorio, Clea B·rcena, Clara Soria-Valles, Andrew J. Ramsay, FÈlix de Carlos, Juan Cobo, Antonio Fueyo, JosÈ M. P. Freije and Carlos LÛpez-OtÌn. 10/15/2012. "Nuclear lamina defects cause ATM-dependent NF-?B activation and link accelerated aging to a systemic inflammatory response." Genes & Development 26: 20: 2311-2324. 10.1101/gad.197954.112.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1101/gad.197954.112 | issn = 1549-5477 | volume = 26 | pages = 2311-2324 | last = Osorio | first = Fernando G. | coauthors = B·rcena, Clea, Soria-Valles, Clara, Ramsay, Andrew J., de Carlos, FÈlix, Cobo, Juan, Fueyo, Antonio, Freije, JosÈ M. P., LÛpez-OtÌn, Carlos | title = Nuclear lamina defects cause ATM-dependent NF-?B activation and link accelerated aging to a systemic inflammatory response | journal = Genes & Development | date = 10/15/2012 | pmid = | pmc = }} </ref>