scholarly journals A TORC1-histone axis regulates chromatin organisation and non-canonical induction of autophagy to ameliorate ageing

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Yu-Xuan Lu ◽  
Jennifer C Regan ◽  
Jacqueline Eßer ◽  
Lisa F Drews ◽  
Thomas Weinseis ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Small Intestine ◽  
Chromatin Organization ◽  
Healthy Longevity ◽  
Age Related ◽  
Elevated Expression ◽  
Chromatin Organisation ◽  
Multicellular Organisms ◽  
Intestinal Enterocytes ◽  
Age Related Changes

Age-related changes to histone levels are seen in many species. However, it is unclear whether changes to histone expression could be exploited to ameliorate the effects of ageing in multicellular organisms. Here we show that inhibition of mTORC1 by the lifespan-extending drug rapamycin increases expression of histones H3 and H4 post-transcriptionally, through eIF3-mediated translation. Elevated expression of H3/H4 in intestinal enterocytes in Drosophila alters chromatin organization, induces intestinal autophagy through transcriptional regulation, prevents age-related decline in the intestine. Importantly, it also mediates rapamycin-induced longevity and intestinal health. Histones H3/H4 regulate expression of an autophagy cargo adaptor Bchs (WDFY3 in mammals), increased expression of which in enterocytes mediates increased H3/H4-dependent healthy longevity. In mice, rapamycin treatment increases expression of histone proteins and Wdfy3 transcription, and alters chromatin organisation in the small intestine, suggesting the mTORC1-histone axis is at least partially conserved in mammals and may offer new targets for anti-ageing interventions.

Age-related changes in the distribution and frequency of myeloid and T cell populations in the small intestine of calves

2011 ◽  
Vol 271 (2) ◽  
pp. 428-437 ◽  
Author(s):  
Patrick N. Fries ◽  
Yurij I. Popowych ◽  
Le Luo Guan ◽  
Philip J. Griebel
Keyword(s):  
Small Intestine ◽  
T Cell ◽  
Cell Populations ◽  
Age Related ◽  
Age Related Changes

scholarly journals Age-related changes in the mRNA levels of CYP1A1, CYP2B1/2 and CYP3A1 isoforms in rat small intestine

2011 ◽  
Vol 7 (2) ◽  
pp. 197-207 ◽  
Author(s):  
Artur Pałasz ◽  
Anna Wiaderkiewicz ◽  
Ryszard Wiaderkiewicz ◽  
Piotr Czekaj ◽  
Beata Czajkowska ◽  
...  
Keyword(s):  
Small Intestine ◽  
Mrna Levels ◽  
Rat Small Intestine ◽  
Age Related ◽  
Age Related Changes

scholarly journals Age-related changes in the proteostasis network in the brain of the naked mole-rat: Implications promoting healthy longevity

2015 ◽  
Vol 1852 (10) ◽  
pp. 2213-2224 ◽  
Author(s):  
Judy C. Triplett ◽  
Antonella Tramutola ◽  
Aaron Swomley ◽  
Jessime Kirk ◽  
Kelly Grimes ◽  
...  
Keyword(s):  
Healthy Longevity ◽  
Age Related ◽  
Mole Rat ◽  
Naked Mole Rat ◽  
The Brain ◽  
Age Related Changes

scholarly journals Transcriptional factor Pdx1 is involved in age-related GIP hypersecretion in mice

2018 ◽  
Vol 315 (2) ◽  
pp. G272-G282
Author(s):  
Eri Ikeguchi ◽  
Norio Harada ◽  
Yoshinori Kanemaru ◽  
Akiko Sankoda ◽  
Shunsuke Yamane ◽  
...  
Keyword(s):  
Small Intestine ◽  
Gastric Inhibitory Polypeptide ◽  
Cell Number ◽  
Transcriptional Factor ◽  
Specific Gene ◽  
Fat Accumulation ◽  
K Cells ◽  
Age Related ◽  
Pdx1 Expression ◽  
Age Related Changes

Fat accumulation with aging is a serious problem; glucose-dependent insulinotropic polypeptide/gastric inhibitory polypeptide (GIP) is an incretin that plays an important role in fat accumulation. GIP receptor knockout mice show reduced fat mass and improved insulin sensitivity associated with aging. Therefore, GIP is involved in fat accumulation and insulin resistance with aging. However, age-related changes of GIP secretion remain unclear. The present study aimed to elucidate age-related changes of GIP secretion and enteroendocrine K cells using GIP reporter [GIP-green fluorescent protein (GFP) knock-in heterozygous (GIPgfp/+)] mice. Aged 1-yr-old GIPgfp/+ mice exhibited a phenotype of fat accumulation, insulin resistance, and GIP hypersecretion compared with young (3–4 mo old) GIPgfp/+ mice. In aged mice, K-cell number in the small intestine and the mRNA expression levels of GIP and transcriptional factor pancreatic and duodenal homeobox-1 (Pdx1) in K cells were increased. K-cell number, GIP mRNA expression and content in small intestine, and GIP secretion were decreased after posteriori suppression of Pdx1 using intestine-specific gene transfer. Thus, Pdx1 positively regulates GIP mRNA and K-cell number in small intestine. Increased Pdx1 expression might be involved in GIP hypersecretion with aging. NEW & NOTEWORTHY Age-related changes of glucose-dependent insulinotropic polypeptide/gastric inhibitory polypeptide (GIP) secretion and K cells were investigated. We found that K-cell number and GIP and pancreatic and duodenal homeobox-1 (Pdx1) expression in K cells were increased in aged mice, which showed greater GIP secretion compared with young mice. In addition, we have succeeded in posteriori suppression of Pdx1 in small intestine using the method of intestine-specific gene transfer, and showed that K-cell number, GIP expression, and GIP secretion were decreased in the Pdx1-knockdown intestine.

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