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Deciphering Aging Linking senescence with DNA Damage and the cell cycle
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Participating Experts: Sheila A. Stewart, PhD (WUSTL) and James L. Kirkland, MD PhD, (Mayo Clinic) • ⬇️ Expand “Show More” to view Abstract and Table of Contents • Download the Senescence Signaling Pathway Diagram: https://cst-science.com/tkawkd • Senescence describes the complex cellular response to stress that includes irreversible arrest of the cell cycle and thus prevention of the proliferation of defective or damaged cells. This effect makes senescence a key component in the body’s tumor suppression response and initialization of repair pathways, providing a health-promoting mechanism. Conversely, senescent cells can accumulate in the affected tissues of persons with age-related diseases such as dementias, arthritis, atherosclerosis, and others—such accumulation is considered a hallmark of aging that drives many age-related pathologies. These seemingly contradictory roles make cellular senescence an interesting research target for developing cancer suppression therapies as well as improving health maintenance and extending the human lifespan. • Table of Contents: • 0:40 Welcome and overview • 2:51 Sheila Stewart speaker profile • 3:33 Age-related stromal changes drive tumorigenesis • 5:12 Senescent fibroblasts promote tumorigenesis • 7:28 Senescent cells express pro-tumorigenic factors • 8:25 Senescent cells and immune cell infiltration are increased with age in human skin • 10:51 Immune infiltration is increased in animal model of accelerated “aging” in the stromal compartment – the FASST mouse • 12:02 Senescent fibroblasts direct the localization of immune cells within FASST skin • 13:36 Senescent cells create an immunosuppressive, tumor permissive microenvironment • 15:02 Does aging impact the premetastatic niche within the bone? • 18:20 Ectopic expression of p27kip induces OB senescence and SASP expression • 19:24 transgene activation leads to IL6 expression in osteoblasts • 20:49 FASST mice with senescent osteoblasts have increased bone metastasis • 23:34 Loss of stromal p38MAPK leads to reduced primary tumor growth • 24:43 CAFs and senescent fibroblasts promote tumorigenesis through common mechanisms • 27:39 Senescent cells express p38-MK2-dependent pro-tumorigenic factors • 29:27 Tumor cells drive increase in osteoclasts, which drives increased tumor cell proliferation • 31:23 p38MAPK and MK2 inhibition inhibits bone metastasis and preserves bone integrity • 33:17 James Kirkland speaker profile • 34:05 Aging, chronic disease, and senolytic drugs • 38:24 Senescence overview • 40:53 Senescent cells accumulate in human adipose tissue with aging • 42:28 Transplanting senescent cells into knees causes osteoarthritis-like joint destruction • 45:05 Transplanted senescent cells spread senescence to host cells • 45:50 networks of anti-apoptotic regulators confer resistance to apoptosis in senescent cells • 49:35 Senolytic agents, senescent cell anti-apoptotic pathways (SCAPs), and cell types targeted • 51:25 D+Q clears transplanted luciferase-expressing senescent preadipocytes • 51:51 D+Q is senolytic in freshly-isolated human adipose tissue • 53:20 Senolytics delay neurologic dysfunction in progeroid mice • 54:14 Senolytics alleviate Alzheimer’s-like changes in Tau+ mice • 56:01 A single dose of senolytics alleviates radiation-induced gait disturbance for 7 months • 58:12 Senolytics reduce intimal calcification in ApoE / atherosclerotic mice • 59:42 Senolytics decrease frailty and extend lifespan in old mice • 1:01:08 Clinical scenarios for testing agents that target aging processes • About CST®: Cell Signaling Technology (CST) is a private, family-owned company, founded by scientists and dedicated to providing high-quality research tools to the biomedical research community. Our employees operate worldwide from our U.S. headquarters in Massachusetts, and our offices in the Netherlands, China, and Japan. https://cellsignal.com/about • Cell Signaling Technology and CST are registered trademarks of Cell Signaling Technology, Inc. All other trademarks are the property of their respective owners. • #antibody #CSTWebinar
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