Table 5.

Improvement of the decline of stem cell functions in ageing individuals by NF-κB blockade.

NF-κB Gene	Genetic Modification	Involvement of NF-κB in the Ageing of Progenitor Cells. Proposed Mechanisms
		Muscle-derived stem/progenitor cells
Rela [172]	Rela haploinsufficient (aged p65+/−) mice.	Aged p65+/− MDSPCs retained myogenic potential in vitro and had a higher resistance to oxidative stress-induced cell death. Genetic inhibition of NF-κB activation increases myogenic differentiation and improves resistance to oxidative stress. 14-day-old and 24-month-old mice were studied.
Ikkβ, nemo [173]	IkkβCAMuSC mice express a constitutively active (CA) form of the Ikkβ gene in MuSCs. NemoKOMuSC: Mice deficient in Nemo subunit in MuSCs. Mdx mice: Dystrophin mutant mouse.	Persistent activation of NF-κB in IkkβCAMuSC mice leads to telomere shortening and impairment of regeneration; in Mdx/IkkβCAMuSC mice it exacerbates the progression of dystrophy. The mechanism involves Ku80 dysregulation (a protein that binds to telomeres, aid the localization of other shelterins, and regulate telomere length) and increased DNA damage, specifically on telomeres, resulting in MuSC loss and, subsequently, skeletal muscle regenerative failure. Mice between 2- and 12 months of age were analyzed.
		Osteoprogenitors
Ikkβ [107]	iNf-κb/OP mice: express a constitutively active mutant IKKβ in osteoprogenitor (OP)-lineage cells, upon Dox withdrawal in skeletally mature mice.	iNf-κb/OP mice showed reduced bone mineral density in the femur and tibia, and increased bone marrow fat, resembling human osteoporosis. Decreased expression levels of osteogenic marker (Runx2 and osteocalcin) and increased adipogenic marker (PPAR-γ and C/EBP) in mesenchymal stem cells (MSCs) of iNf-κb/OP mice. Mice of 12 and 36 weeks of age were studied.