| First Author | Osorio FG | Year | 2012 |
| Journal | Genes Dev | Volume | 26 |
| Issue | 20 | Pages | 2311-24 |
| PubMed ID | 23019125 | Mgi Jnum | J:188267 |
| Mgi Id | MGI:5440109 | Doi | 10.1101/gad.197954.112 |
| Citation | Osorio FG, et al. (2012) Nuclear lamina defects cause ATM-dependent NF-kappaB activation and link accelerated aging to a systemic inflammatory response. Genes Dev 26(20):2311-24 |
| abstractText | 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-kappaB 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-kappaB in accelerated aging was demonstrated by the fact that both genetic and pharmacological inhibition of NF-kappaB 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-kappaB pathway to slow down the progression of physiological and pathological aging. |
