Please use this identifier to cite or link to this item: http://hdl.handle.net/2067/48981
Title: Young transgenic hMTH1 mice are protected against dietary fat-induced metabolic stress—implications for enhanced longevity
Authors: Marcon, Francesca
Meschini, Roberta 
Iorio, Egidio
Palleschi, Simonetta
De Luca, Gabriele
Siniscalchi, Ester
Conti, Luigi
Chirico, Mattea
Pisanu, Maria Elena
De Battistis, Francesca
Rossi, Barbara
Minoprio, Anna
Giuliani, Alessandro
Karran, Peter
Bignami, Margherita
Journal: AGING CELL 
Issue Date: 2022
Abstract: 
hMTH1 protects against mutation during oxidative stress. It degrades 8-oxodGTP to exclude potentially mutagenic oxidized guanine from DNA. hMTH1 expression is linked to ageing. Its downregulation in cultured cells accelerates RAS-induced senescence, and its overexpression in hMTH1-Tg mice extends lifespan. In this study, we analysed the effects of a brief (5 weeks) high-fat diet challenge (HFD) in young (2 months old) and adult (7 months old) wild-type (WT) and hMTH1-Tg mice. We report that at 2 months, hMTH1 overexpression ameliorated HFD-induced weight gain, changes in liver metabolism related to mitochondrial dysfunction and oxidative stress. It prevented DNA damage as quantified by a comet assay. At 7 months old, these HFD-induced effects were less severe and hMTH1-Tg and WT mice responded similarly. hMTH1 overexpression conferred lifelong protection against micronucleus induction, however. Since the canonical activity of hMTH1 is mutation prevention, we conclude that hMTH1 protects young mice against HFD by reducing genome instability during the early period of rapid growth and maximal gene expression. hMTH1 protection is redundant in the largely non-growing, differentiated tissues of adult mice. In hMTH1-Tg mice, expression of a less heavily mutated genome throughout life provides a plausible explanation for their extended longevity.
URI: http://hdl.handle.net/2067/48981
ISSN: 1474-9726
DOI: 10.1111/acel.13605
Rights: Attribution 4.0 International
Appears in Collections:A1. Articolo in rivista

Files in This Item:
File Description SizeFormat
Marcon et al.pdf1.47 MBAdobe PDFView/Open
Show full item record

SCOPUSTM   
Citations

4
Last Week
0
Last month
checked on Mar 22, 2024

Page view(s)

42
Last Week
0
Last month
1
checked on Mar 27, 2024

Download(s)

5
checked on Mar 27, 2024

Google ScholarTM

Check

Altmetric


This item is licensed under a Creative Commons License Creative Commons