PMID- 33233021
OWN - NLM
STAT- MEDLINE
DCOM- 20210818
LR  - 20210818
IS  - 1447-0594 (Electronic)
IS  - 1447-0594 (Linking)
VI  - 21
IP  - 1
DP  - 2021 Jan
TI  - Bioinformatics analysis of autophagy-lysosomal degradation in cardiac aging.
PG  - 108-115
LID - 10.1111/ggi.14098 [doi]
AB  - AIM: Cardiac aging, which causes cardiac diastolic dysfunction, frequently occurs 
      in older people. The role of autophagy in cardiac aging is the subject of 
      intensive research. Autophagy comprises steps called the autophagosome formation 
      and autophagosome-lysosome fusion. Caloric restriction (CR) is the gold standard 
      used to induce autophagosome formation, and autophagosome-lysosome fusion is 
      reduced by aging. However, few studies are available that survey and compare 
      signaling during CR (autophagosome formation induced status) and old (potentially 
      autophagosome-lysosome fusion-reduced status). Here we aimed to identify the 
      rate-limiting step of autophagic disorders during cardiac aging. METHODS: We 
      employed bioinformatics to analyze publicly available DNA microarray datasets. 
      The first dataset compared the hearts of young and old C57BL6 mice (OLD). The 
      second dataset compared the hearts of young C57BL6 mice fed a normal diet with 
      those of young C57BL6 mice subjected to CR. RESULTS: We analyzed OLD-upregulated 
      genes that were significantly associated with the Gene Ontogeny term "Autophagy," 
      indicating that autophagic genes were upregulated in OLD mice. The 
      autophagy-related gene Atg5 and Atg5-related genes were upregulated in OLD and CR 
      mice. The identified hub and bottleneck genes are autophagic autophagosome 
      formation suppressors such as Sirt2, Ilk and Islr, as well as the 
      autophagosome-lysosome fusion inducer Snapin. CONCLUSIONS: Autophagosome 
      formation genes were upregulated in aging mice subjected to CR, indicating that 
      an upregulated autophagosome formation is not a change specific to cardiac aging. 
      However, autophagosome-lysosome fusion genes, particularly the lysosome 
      transportation-related gene Snapin, were downregulated in aging, indicating that 
      autophagosome-lysosome fusion may cause autophagic disorders in cardiac aging. 
      Geriatr Gerontol Int 2021; 21: 108-115.
CI  - (c) 2020 Japan Geriatrics Society.
FAU - Kamihara, Takahiro
AU  - Kamihara T
AUID- ORCID: 0000-0003-4592-4170
AD  - Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, 
      Japan.
FAU - Murohara, Toyoaki
AU  - Murohara T
AD  - Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, 
      Japan.
LA  - eng
PT  - Journal Article
DEP - 20201124
PL  - Japan
TA  - Geriatr Gerontol Int
JT  - Geriatrics & gerontology international
JID - 101135738
RN  - 0 (Snapin protein, mouse)
RN  - 0 (Vesicular Transport Proteins)
SB  - IM
MH  - Aging/genetics
MH  - Animals
MH  - Autophagy
MH  - *Computational Biology
MH  - *Lysosomes
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Vesicular Transport Proteins
OTO - NOTNLM
OT  - aging
OT  - autophagy
OT  - cardiology
OT  - computational biologyly
OT  - sosomes
EDAT- 2020/11/25 06:00
MHDA- 2021/08/19 06:00
CRDT- 2020/11/24 20:12
PHST- 2020/09/24 00:00 [received]
PHST- 2020/10/21 00:00 [revised]
PHST- 2020/11/03 00:00 [accepted]
PHST- 2020/11/25 06:00 [pubmed]
PHST- 2021/08/19 06:00 [medline]
PHST- 2020/11/24 20:12 [entrez]
AID - 10.1111/ggi.14098 [doi]
PST - ppublish
SO  - Geriatr Gerontol Int. 2021 Jan;21(1):108-115. doi: 10.1111/ggi.14098. Epub 2020 
      Nov 24.