Abstract
Senescent astrocytes in aging brain express senescence-associated secretory phenotype (SASP) and link with increased brain aging and its related diseases. In order to determine whether ginsenosides ameliorate the astrocytic senescence in vitro, human astrocytic CRT cells and primary rat astrocytes were used in the present study. Ginsenosides Rg1, Re, Rb1 and Rg3 (5 μg/mL) could effectively prevent the astrocytic senescence induced by H2O2 exposure. However, these ginsenosides did not reverse the astrocytic senescence. Importantly, senescent astrocytes herein produce SASP. The expression of major components of SASP, IL-6 and IL-8, are greatly increased in senescent astrocytes. Ginsenoside Rg3 (10 μg/mL) effectively suppressed the expressions of IL-6 and IL-8, which is associated with regulations of NF-κB and p38MAPK activation. In addition, after incubation with Rg3, conditioned medium from senescent astrocytic CRT cells significantly decreased the ability to promote the proliferation of astrocytoma U373-MG, U87-MG and U251-MG cells compared with non-treated senescent samples. Similar patterns were confirmed in chemotherapy-induced glioblastoma senescent cells. The present study explored a potential candidate for amelioration of astrocytic senescence and SASP in brain aging, which provided a basis for developing strategies to reduce the dark side of senescence in normal or pathological aging process.
Highlights
Aging is characterized by a progressive loss of physiological function, giving rise to tissue dysfunction and increased vulnerability to diseases and death
The hallmarks of aging are summarized to identify pharmaceutical targets and improve human healthy lifespan. One of the these hallmarks is cellular senescence, which have a complex phenotype characterized by irreversible cell-cycle arrest mediated predominated by p16ink4a and p21, increased cellular size, altered morphology, resistance to apoptosis, and a unique secretory phenotype referred as senescent-associated secretory phenotype (SASP) [1]
Our results confirmed that oxidative stress induces astrocytic senescence and possible brain tumorigenesis process that involves SASP
Summary
Aging is characterized by a progressive loss of physiological function, giving rise to tissue dysfunction and increased vulnerability to diseases and death. The hallmarks of aging are summarized to identify pharmaceutical targets and improve human healthy lifespan. One of the these hallmarks is cellular senescence, which have a complex phenotype characterized by irreversible cell-cycle arrest mediated predominated by p16ink4a and p21, increased cellular size, altered morphology, resistance to apoptosis, and a unique secretory phenotype referred as senescent-associated secretory phenotype (SASP) [1]. Researches on the causes and mechanisms underlying the various types of cellular senescence are still in its infancy, telomere erosion, DNA lesion and reactive oxidation species (ROS). H2 O2 is the major precursor of ROS that may result in cellular damage and its excessive accumulation The damaging ROS known to be responsible for neurotoxicity are hydrogen peroxide (H2 O2 ), superoxide anions (O2 − ) and hydroxyl radicals (OH).
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