| First Author | Zhang L | Year | 2021 |
| Journal | Aging Cell | Volume | 20 |
| Issue | 12 | Pages | e13486 |
| PubMed ID | 34734460 | Mgi Jnum | J:320250 |
| Mgi Id | MGI:6841042 | Doi | 10.1111/acel.13486 |
| Citation | Zhang L, et al. (2021) Novel small molecule inhibition of IKK/NF-kappaB activation reduces markers of senescence and improves healthspan in mouse models of aging. Aging Cell 20(12):e13486 |
| abstractText | Constitutive NF-kappaB activation is associated with cellular senescence and stem cell dysfunction and rare variants in NF-kappaB family members are enriched in centenarians. We recently identified a novel small molecule (SR12343) that inhibits IKK/NF-kappaB activation by disrupting the association between IKKbeta and NEMO. Here we investigated the therapeutic effects of SR12343 on senescence and aging in three different mouse models. SR12343 reduced senescence-associated beta-galactosidase (SA-beta-gal) activity in oxidative stress-induced senescent mouse embryonic fibroblasts as well as in etoposide-induced senescent human IMR90 cells. Chronic administration of SR12343 to the Ercc1(-/) () and Zmpste24(-/-) mouse models of accelerated aging reduced markers of cellular senescence and SASP and improved multiple parameters of aging. SR12343 also reduced markers of senescence and increased muscle fiber size in 2-year-old WT mice. Taken together, these results demonstrate that IKK/NF-kappaB signaling pathway represents a promising target for reducing markers of cellular senescence, extending healthspan and treating age-related diseases. |
