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Title: Inhibition of Cdc42 activity extends lifespan and decreases circulating inflammatory cytokines in aged female C57BL/6 mice
Author: Florian, Maria Carolina
Leins, Hanna
Gobs, Michael
Han, Yang
Marka, Gina
Soller, Karin
Vollmer, Angelika
Sakk, Vadim
Nattamai, Kalpana J.
Rayes, Ahmad
Zhao, Xueheng
Setchell, Kenneth
Mulaw, Medhanie
Wagner, Wolfgang
Zheng, Yi
Geiger, Hartmut
Keywords: Cèl·lules eucariotes
Ratolins (Animals de laboratori)
Eukaryotic cells
Mice (Laboratory animals)
Issue Date: 4-Aug-2020
Publisher: Wiley
Abstract: Cdc42 is a small RhoGTPase regulating multiple functions in eukaryotic cells. The activity of Cdc42 is significantly elevated in several tissues of aged mice, while the Cdc42 gain-of-activity mouse model presents with a premature aging-like phenotype and with decreased lifespan. These data suggest a causal connection between elevated activity of Cdc42, aging, and reduced lifespan. Here, we demonstrate that systemic treatment of aged (75-week-old) female C57BL/6 mice with a Cdc42 activity-specific inhibitor (CASIN) for 4 consecutive days significantly extends average and maximum lifespan. Moreover, aged CASIN-treated animals displayed a youthful level of the aging-associated cytokines IL-1β, IL-1α, and INFγ in serum and a significantly younger epigenetic clock as based on DNA methylation levels in blood cells. Overall, our data show that systemic administration of CASIN to reduce Cdc42 activity in aged mice extends murine lifespan.
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It is part of: Aging Cell, 2020, vol. 19, num. 9, p. e13208
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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