Sirt1 Protects Subventricular Zone-Derived Neural Stem Cells from DNA Double-Strand Breaks and Contributes to Olfactory Function Maintenance in Aging Mice.
Jie RenXianli WangChuanming DongGuang-Ming WangWenjun ZhangChunhui CaiMinxian QianDanjing YangBin LingKe NingZhiyong MaoBao-Hua LiuTinghua WangLiuliu XiongWenyuan WangAibin LiangZhengliang GaoJun XuPublished in: Stem cells (Dayton, Ohio) (2022)
DNA damage is assumed to accumulate in stem cells over time and their ability to withstand this damage and maintain tissue homeostasis is the key determinant of aging. Nonetheless, relatively few studies have investigated whether DNA damage does indeed accumulate in stem cells and whether this contributes to stem cell aging and functional decline. Here, we found that, compared with young mice, DNA double-strand breaks (DSBs) are reduced in the subventricular zone (SVZ)-derived neural stem cells (NSCs) of aged mice, which was achieved partly through the adaptive upregulation of Sirt1 expression and non-homologous end joining (NHEJ)-mediated DNA repair. Sirt1 deficiency abolished this effect, leading to stem cell exhaustion, olfactory memory decline, and accelerated aging. The reduced DSBs and the upregulation of Sirt1 expression in SVZ-derived NSCs with age may represent a compensatory mechanism that evolved to protect stem cells from excessive DNA damage, as well as mitigate memory loss and other stresses during aging.
Keyphrases
- dna damage
- stem cells
- dna repair
- oxidative stress
- poor prognosis
- ischemia reperfusion injury
- high fat diet induced
- dna damage response
- cell therapy
- circulating tumor
- neural stem cells
- working memory
- single molecule
- signaling pathway
- cell free
- cell proliferation
- long non coding rna
- binding protein
- skeletal muscle
- weight loss
- insulin resistance
- body mass index
- smoking cessation
- physical activity
- case control
- replacement therapy