Biology of extracellular vesicles secreted from senescent cells as senescence‐associated secretory phenotype factors

Abstract

The increase of the morbidity rate in age‐related diseases, such as cancer, Alzheimer’s disease, arteriosclerosis and pulmonary fibrosis, has become a profound social problem. Recent reports have pointed out that senescent cells accumulated in the body with aging might cause these aged‐related pathologies. Cellular senescence is known as an irreversible cell cycle arrest induced by various stresses, and can function as an important tumor suppression mechanism to exclude the premalignant cells. In contrast, senescent cells provoke the phenomenon, termed the senescence‐associated secretory phenotype, which causes the secretion of various inflammatory proteins, and it is at risk of facilitating chronic inflammation and oncogenic transformation to surrounding cells. We have previously reported that senescent cells secrete not only inflammatory proteins, but also extracellular vesicles (EV). EV include various cellular components, such as proteins, lipids and nucleic acids, which are proven to be important factors for cell‐to‐cell communication. Recent evidence suggests that EV secreted from senescent cells might contribute to tumorigenesis and age‐associated pathologies as new senescence‐associated secretory phenotype factors. In addition, we also showed that the EV secretion pathway is one of the essential defense mechanisms to maintain cellular homeostasis by excretion of intercellular toxic substances into extracellular space. Herein, this review shows the biological functions of EV secreted from senescent cells. Geriatr Gerontol Int 2020; ••: ••–••.

Identifying Blood Transcriptome Biomarkers of Alzheimer’s Disease Using Transgenic Mice

“…The expression of five gene transcripts ( Cdkn2a , Apobec3 , Magi2 , Parp3 , and Cass4 ) significantly increased with age, and their expression in the blood was correlated to that in the hippocampus only in AD mice (Table 3 ). CDKN2A is a well-known molecular player in cellular senescence, cell proliferation, survival, adhesion, and apoptosis [ 23 , 24 ]. An increased level of Cdkn2a is present in both brain and blood cells from APP/PS1 mice [ 29 ].…”

“…To verify the reliability of the microarray data, we selected Cdkn2a for qPCR experiments because this gene exhibited the greatest changes among the five candidate genes and is well known as an aging-and cellular senescence-associated gene [23,24]. This analysis aimed to not only validate the correlations between the microarray and real-time PCR data but also confirm the detection of well-known changes.…”

Extracellular Vesicles for the Treatment of Radiation Injuries

“…This process collectively refers to as senescence-associate secretory phenotype (SASP) ( Li et al, 2018 ). The molecules secreted from SASP can also be packed in EV format ( Misawa et al, 2020 ). This persistent insult from SASP leads to the delayed effect of irradiation-induced senescence, such as fibrosis in the lung ( Citrin et al, 2013 ; He et al, 2019 ), oral mucositis ( Iglesias-Bartolome et al, 2012 ), cardiovascular disease ( Stewart et al, 2013 ), hypo-salivation ( Peng et al, 2020 ), hematopoietic cell senescence ( Wang et al, 2011 ).…”

“…In another study, downregulation of antioxidant enzyme genes and cellular redox system (iNOS2) genes was observed in non-irradiated mice as a bystander effect when injected with bone marrow-EVs from irradiated mice ( Hargitai et al, 2021 ). In the same token, recent evidence suggests that EVs as SASP, secreted from senescent cells might contribute to tumorigenesis and age-associated pathologies ( Misawa et al, 2020 ). It can be a potential mechanism to explain a high incidence of cancer developed in the survivors after radiation exposure.…”

Inhibition of the P53/P21 Pathway Attenuates the Effects of Senescent Nucleus Pulposus Cell‐Derived Exosomes on the Senescence of Nucleus Pulposus Cells

“…SASP has been regarded as a critical factor in the occurrence and development of age-related diseases 7 . Some studies have indicated that senescent cells secrete not only inflammatory cytokines, chemokines, and matrix metalloproteinases but also exosomes 8 . Exosomes are double-layered membrane vesicles secreted by cells and play a crucial role in the material exchange and information transduction between cells 9 .…”