RRC ID 57295
Author Jeon HJ, Kim YS, Kim JG, Heo K, Pyo JH, Yamaguchi M, Park JS, Yoo MA.
Title Effect of heterochromatin stability on intestinal stem cell aging in Drosophila.
Journal Mech Ageing Dev
Abstract Chromatin change is one of the crucial causes of aging. Specifically, maintenance of heterochromatin stability is critical for cellular integrity, and its loss induces genomic instability and cellular aging. However, the causes and effects of heterochromatin instability in multicellular tissue aging still remain unclear. Here, in the adult Drosophila midgut, we report age-related loss of heterochromatin stability in enterocytes (ECs) due to the loss and dispersion of tri-methylated histone H3 Lys9 (H3K9me3) and heterochromatin protein 1 (HP1). Our study further shows that EC-specific knockdown of Su(var)3-9, histone lysine methyltransferase for H3K9me3 formation, or HP1a leads to intestinal stem cell (ISC) aging through genomic stress, JNK signaling, and apoptotic death in ECs. Our findings revealed the plausible causes of age-related loss of heterochromatin stability in ECs, including oxidative stress and nutrient-sensing AKT/TOR signaling. Taken together, the loss of heterochromatin stability may be the crucial niche aging mechanism for ISC aging which is the prime determinant of intestinal tissue aging. Furthermore, our study provides new clues on the link between heterochromatin and aging.
Volume 173
Pages 50-60
Published 2018-7-1
DOI 10.1016/j.mad.2018.04.001
PII S0047-6374(17)30292-0
PMID 29625135
MeSH Aging / genetics Aging / metabolism* Aging / pathology Animals Drosophila Proteins / genetics Drosophila Proteins / metabolism Drosophila melanogaster Gene Knockdown Techniques Heterochromatin / genetics Heterochromatin / metabolism* Heterochromatin / pathology Histone-Lysine N-Methyltransferase / genetics Histone-Lysine N-Methyltransferase / metabolism Intestinal Mucosa / metabolism* Intestines / pathology Signal Transduction* Stem Cells / metabolism* Stem Cells / pathology
IF 3.603
Times Cited 7