Reactive oxygen species produced in mitochondria are involved in age-dependent changes of hematopoietic and mesenchymal progenitor cells in mice. A study with the novel mitochondria-targeted antioxidant SkQ1.
Lifelong treatment of mice with the effective mitochondria-targeted antioxidant SkQ1 [10-(6'-plastoquinonyl) decyltriphenylphosphonium] does not affect hematopoietic stem cells (HSC) and more differentiated hematopoietic progenitors but significantly decelerates age-dependent changes in peripheral blood. During the first 13 months, SkQ1 (0.9 or 28.8 nmol/kg day) prevents age-dependent myeloid shift (increase in the proportion of granulocytes and decrease in the proportion of lymphocytes). During the next year of treatment the effect disappears, and the hemogram of 2-year-old treated mice does not differ from the control. The number of mesenchymal stem cells (MSC) in the bone marrow does not change during 2 years of treatment with SkQ1, but the concentration of MSC progeny fibroblast colony-forming units (CFU-F) increases with dose of SkQ1. The concentration of CFU-F after 1 and 2 years treatment with SkQ1 is twice higher than in young mice. Our data indicate that the stromal environment of hematopoietic cells could be the primary target of age-dependent changes mediated by reactive oxygen species produced in mitochondria. The anti-aging effects of SkQ1 described here are in perfect agreement with the inhibitory effects of this antioxidant on aging observed in the other models.
Shipounova
I N
IN
National Hematological Research Center, Russian Academy of Medical Sciences, Moscow, Russian Federation.
Svinareva
D A
DA
Petrova
T V
TV
Lyamzaev
K G
KG
Chernyak
B V
BV
Drize
N I
NI
Skulachev
V P
VP
D000375:Aging / Q000187:drug effects*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D005260:Female; D006098:Granulocytes / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000187:drug effects*; D010971:Plastoquinone / Q000031:analogs & derivatives* / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism
C532038:10-(6'-plastoquinonyl)decyltriphenylphosphonium; D000975:Antioxidants; D017382:Reactive Oxygen Species; D010971:Plastoquinone