Identification of a novel senomorphic agent, avenanthramide C, via the suppression of the senescence-associated secretory phenotype. (December 2020)

• Record Type: Journal Article
• Authors: Lim, Jae Sung; Lee, Da Young; Kim, Hyung Seok; Park, Sang Chul; Park, Joon Tae; Kim, Hyeon Sik; Oh, Won Keun; Cho, Kyung A.
• Is Part Of: Mechanisms of ageing and development. Volume 192(2020)
• Publication Date: 2020-12
• Subjects: Senescent cells -- Senescence-associated secretory phenotype (SASP) -- Avenanthramide C -- Senomorphic; Aging -- Periodicals; Developmental biology -- Periodicals; Aging -- Periodicals; Developmental Biology -- Periodicals; Vieillissement -- Périodiques; Biologie du développement -- Périodiques; Aging; Developmental biology; Periodicals; 612.67
• DOI: 10.1016/j.mad.2020.111355
• Languages: English
• ISSNs: 0047-6374

Abstract

Highlights: Avn C lead a rescue of the senescence phenotypes. Avn C plays a different role in inhibiting NF-κB signaling between LPS-induced inflammation and inflammaging. Avn C can be a good candidate for the SASP modulator. Abstract: Senescent cells are deeply involved in the induction of tissue damage and aging-related diseases. The identification of factors that eliminate senescent cells or inhibit the senescence-associated secretory phenotype (SASP) in these cells is necessary. Here, we report an avenanthramice C (Avn C) extracted from oat as a new SASP modulator. Treatment with Avn C led to a significant reduction in the levels of markers of senescent cells, with no toxicity observed. The SASP was also inhibited by Avn C treatment, similar to non-senescent cells, and the suppression of cell division by autocrine signals associated with SASP was restored. To investigate the mechanism underlying SASP inhibition by Avn C, we analyzed the effect of Avn C in lipopolysaccharide (LPS)-induced inflammation in non-senescent cells. Avn C inhibited nuclear factor κB (NF-κB) activity and the secretion of inflammatory cytokines before or after LPS treatment. Although the activity of MAP kinases, which are NF-κB upstream signals, was inhibited by Avn C in LPS-induced inflammation, only p38 activity was specifically inhibited in senescent cells. Interestingly, the inhibition of p38 in senescent cells was observed through Avn C-induced 5′-adenosine monophosphate-activated protein kinase (AMPK) activity. Avn C-induced inhibition of the SASP is triggered by senescence-related stress.