Relief of oxidative stress by ascorbic acid delays cellular senescence of normal human and Werner syndrome fibroblast cells.
Primary human cells have a definite life span and enter into cellular senescence before ceasing cell growth. Oxidative stress produced by aerobic metabolism has been shown to accelerate cellular senescence. Here, we demonstrated that ascorbic acid, used as an antioxygenic reagent, delayed cellular senescence in a continuous culture of normal human embryonic cells, human adult skin fibroblast cells, and Werner syndrome (WS) cells. The results using human embryonic cells showed that treatment with ascorbic acid phospholic ester magnesium salt (APM) decreased the level of oxidative stress, and extended the replicative life span. The effect of APM to extend the replicative life span was also shown in normal human adult cells and WS cells. To understand the mechanism of extension of cellular life span, we determined the telomere lengths of human embryonic cells, both with and without APM treatment, and demonstrated that APM treatment reduced the rate of telomere shortening. The present results indicate that constitutive oxidative stress plays a role in determining the replicative life span and that suppression of oxidative stress by an antioxidative agent, APM, extends the replicative life span by reducing the rate of telomere shortening.
Kashino
Genro
G
Division of Radiation Biology, Department of Radiology and Radiation Biology, Course of Life Sciences and Radiation Research, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Kodama
Seiji
S
Nakayama
Yukiko
Y
Suzuki
Keiji
K
Fukase
Kazuaki
K
Goto
Makoto
M
Watanabe
Masami
M
D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000378:metabolism / Q000494:pharmacology*; D002455:Cell Division; D002460:Cell Line; D002478:Cells, Cultured; D016922:Cellular Senescence; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D018384:Oxidative Stress; D016615:Telomere / Q000378:metabolism / Q000648:ultrastructure; D013997:Time Factors; D014898:Werner Syndrome / Q000378:metabolism*
D000975:Antioxidants; D001205:Ascorbic Acid