aging United States | DDIT4 has been identified as a candidate target

aging United States |  DDIT4 has been identified as a candidate target for HDAC4-related skin aging

image: Figure 2. Integrative transcriptional analysis identifies DDIT4 as a candidate target.
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Credit: Nachin et al.

Buffalo, New York – June 15, 2022 – A new research paper has been published in aging (US aging) on the cover Volume 14, Issue 11authorized, “Histone deacetylase 4 reverses cellular senescence via DDIT4 in dermal fibroblasts. “

The researchers — from Seoul National University, Seoul National University School of Medicine, Seoul National University Graduate School, and Daegu Gyeongbuk Institute of Science and Technology (DGIST) — previously demonstrated that histone deacetylase 4 (HDAC4) is consistently reduced in aging and ultraviolet (UV) radiation. )) – irradiated human skin. However, there is little research on how HDAC4 causes skin aging.

“To elucidate the potential role of HDAC4 in the regulation of cellular senescence and skin aging, we established oxidative and UV-induced cellular senescence models using human primary dermal fibroblasts (HDFs).”

After overexpression or knockdown of HDAC4 in primary HDFs, RNA sequencing identified the candidate molecular targets of HDAC4.

“Integrative analyzes of current and public mRNA expression profiles identified DNA damage-inducing transcript 4 (DDIT4) as a critical aging factor regulated by HDAC4.”

Although the function of DDIT4 has been extensively investigated in the areas of cancer and autophagy, little is known about its role in skin aging. The researchers found that DDIT4 expression was significantly decreased in aging skin in vivo, in proliferating HDFs, and in senescent fibroblasts under repeated H₂O₂ or UV-irradiation treatment. During oxidative stress and UV-induced aging, both DDIT4 and HDAC4 expressions were reduced.

In addition, HDAC4 overexpression rescues cells from the senescence-induced deficiency of DDIT4 and the senescent phenotype (which was prevented by DDIT4 knockdown). DDIT4 overexpression reversed changes in senescence-related secretory phenotypes and senescence-related genes, indicating that DDIT4 mediates reversal of cellular senescence via HDAC4.

“Collectively, our results identify DDIT4 as a promising target regulated by HDAC4 associated with cellular aging and epigenetic skin aging.”

“These findings provide new insights into the regulatory role of the HDAC4-DDIT4 pathway in epigenetic skin aging.”

DOI: https://doi.org/10.18632/aging.204118

Corresponding authors: Dahi Huang, Dong Hun Lee, Jin Ho Chung

E-mail: daehee@snu.ac.krAnd the ivymed27@snu.ac.krAnd the jhchung@snu.ac.kr

Key words: Cellular senescence, DNA damage transcript 4, histone deacetylase 4, oxidative stress, UV radiation

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It was launched in 2009, aging (US aging) She publishes papers of general interest and biological significance in all areas of research on aging and age-related disease, including cancer — and now, with a particular focus on the vulnerability of COVID-19 as an age-dependent syndrome. Topics in aging Transcending traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, and signal transduction pathways (eg, p53, sirtuins, and PI-3K/AKT/ mTOR, among others), and approaches to modify these signaling pathways.

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