IGFBP7 is a key component of the senescence-associated secretory phenotype (SASP) that induces senescence in healthy cells by modulating the insulin, IGF, and activin A pathways

Nov 13, 2024Cell communication and signaling : CCS

IGFBP7 triggers aging in healthy cells by affecting insulin, IGF, and activin A pathways as part of the aging cell secretions

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Abstract

The study identified that IGFBP7 plays a significant role in promoting cellular senescence.

Senescent cells release factors known as the senescence-associated secretory phenotype (), which can induce in healthy cells.
Reactive oxygen species (ROS) and prostaglandin signaling are involved in the release of IGFBP7.
Neutralizing antibodies against IGFBP7 reduced the SASP's ability to induce senescence.
IGFBP7 induces senescence by binding to insulin, inhibiting its growth-promoting effects.
IGFBP7 may enhance pro-senescence signaling from IGFII while blocking signals from IGF1R, dependent on specific cellular pathways.
Preliminary data suggest IGFBP7 interacts with Activin A and its receptors, potentially inducing senescence through SMAD pathways.

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Senescent cells exert their effects through the release of various factors, collectively referred to as the senescence-associated secretory phenotype (). The SASP can induce senescence in healthy cells (), modulate immune system function, reshape the extracellular matrix, and facilitate cancer progression.Among SASP components, certain factors act as key regulators in the induction of secondary senescence. In this study, we evaluated the role of IGFBP7, a crucial SASP component. Our results demonstrated that ROS-prostaglandin signaling is involved in the release of IGFBP7. Furthermore, neutralizing antibodies targeting IGFBP7 attenuated the SASP's pro-senescence activity. Cells incubated with IGFBP7 also entered a state of senescence.The senescence induced by IGFBP7 appears to be mediated through three primary pathways. First, IGFBP7 can bind to insulin, thereby inhibiting its anti-senescence and pro-growth effects. In addition to this inhibitory effect on the insulin pathway, IGFBP7 may enhance IGFII pro-senescence signaling by promoting its interaction with IGF2R while blocking IGF1R. These activities are dependent on ERK and AKT signaling pathways. Finally, IGFBP7 and Activin A, both of which can induce cellular senescence, appear to regulate and inhibit each other, suggesting a compensatory mechanism to prevent excessive senescence. Notably, our preliminary data indicate that IGFBP7, in addition to blocking Activin A, may interact with its receptors and induce senescence via SMAD pathways.Our findings highlight that IGFBP7, along with other members of the IGFBP family, plays a pivotal role in senescence-related signaling pathways. Therefore, IGFBP7 may serve as a potential target for anti-aging strategies aimed at reducing the burden of senescence on tissues and organs.

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IGFBP7 is a key component of the senescence-associated secretory phenotype (SASP) that induces senescence in healthy cells by modulating the insulin, IGF, and activin A pathways

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