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pmid:34229541

Declined expressions of vast mitochondria-related genes represented by CYCS and transcription factor ESRRA in skeletal muscle aging.

Jingbao Kan · Yifang Hu · Yaoqi Ge · WenSong Zhang · Shan Lu · Cuiping Zhao · Rihua Zhang · Yun Liu

Bioengineered · 2021 doi:10.1080/21655979.2021.1948951

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complete

Experiment

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Data

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Analysis

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title
Declined expressions of vast mitochondria-related genes represented by CYCS and transcription factor ESRRA in skeletal muscle aging.
doi
10.1080/21655979.2021.1948951
pmid
34229541
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[0]
Jingbao Kan
[1]
Yifang Hu
[2]
Yaoqi Ge
[3]
WenSong Zhang
[4]
Shan Lu
[5]
Cuiping Zhao
[6]
Rihua Zhang
[7]
Yun Liu
journal
Bioengineered
year
2021
abstract
Age-related skeletal muscle deterioration (sarcopenia) has a significant effect on the elderly's health and quality of life, but the molecular and gene regulatory mechanisms remain largely unknown. It is necessary to identify the candidate genes related to skeletal muscle aging and prospective therapeutic targets for effective treatments. The age-line-related genes (ALRGs) and age-line-related transcripts (ALRTs) were investigated using the gene expression profiles of GSE47881 and GSE118825 from the Gene Expression Omnibus (GEO) database. The protein-protein interaction (PPI) networks were performed to identify the key molecules with Cytoscape, and Gene Set Enrichment Analysis (GSEA) was used to clarify the potential molecular functions. Two hub molecules were finally obtained and verified with quantitative real-time PCR (qRT-PCR). The results showed that the expression of mitochondria genes involved in mitochondrial electron transport, complex assembly of the respiratory chain, tricarboxylic acid cycle, oxidative phosphorylation, and ATP synthesis were down-regulated in skeletal muscle with aging. We further identified a primary hub gene of CYCS (Cytochrome C) and a key transcription factor of ESRRA (Estrogen-related Receptor Alpha) to be associated closely with skeletal muscle aging. PCR analysis confirmed the expressions of CYCS and ESRRA in gastrocnemius muscles of mice of different ages were significantly different, and decreased gradually with age. In conclusion, the main cause of skeletal muscle aging may be the systematically reduced expression of mitochondrial functional genes. The CYCS and ESRRA may play significant roles in the progression of skeletal muscle aging and serve as potential biomarkers for future diagnosis and treatment.
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The relationships between ages and gene expressions in the GSE47881 and GSE118825 datasets were performed by Pearson correlation analysis and linear analysis.
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The datasets presented in this study can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo/).
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licence_read
false
[7] object · 15 fields
id
data:geo:GSE4667
role
raw
format
geo-series
media_type
application/vnd.ncbi.geo-series+json
uri
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE4667
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE4667
version
null
note
The datasets presented in this study can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo/).
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The datasets presented in this study can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo/).
access_statement_kind
data_availability_statement
sample_accessions array · 70 items
[0]
GSM105069
[1]
GSM105070
[2]
GSM105071
[3]
GSM105072
[4]
GSM105073
[5]
GSM105074
[6]
GSM105075
[7]
GSM105076
[8]
GSM105077
[9]
GSM105078
[10]
GSM105079
[11]
GSM105080
[12]
GSM105081
[13]
GSM105082
[14]
GSM105083
[15]
GSM105084
[16]
GSM105085
[17]
GSM105086
[18]
GSM105087
[19]
GSM105088
[20]
GSM105089
[21]
GSM105090
[22]
GSM105091
[23]
GSM105092
[24]
GSM105093
[25]
GSM105094
[26]
GSM105095
[27]
GSM105096
[28]
GSM105097
[29]
GSM105098
[30]
GSM105099
[31]
GSM105100
[32]
GSM105101
[33]
GSM105102
[34]
GSM105103
[35]
GSM105104
[36]
GSM105105
[37]
GSM105106
[38]
GSM105107
[39]
GSM105108
[40]
GSM105109
[41]
GSM105110
[42]
GSM105111
[43]
GSM105112
[44]
GSM105113
[45]
GSM105114
[46]
GSM105115
[47]
GSM105116
[48]
GSM105117
[49]
GSM105118
[50]
GSM105119
[51]
GSM105120
[52]
GSM105121
[53]
GSM105122
[54]
GSM105123
[55]
GSM105124
[56]
GSM105125
[57]
GSM105126
[58]
GSM105127
[59]
GSM105128
[60]
GSM105129
[61]
GSM105130
[62]
GSM105131
[63]
GSM105132
[64]
GSM105133
[65]
GSM105134
[66]
GSM105135
[67]
GSM105136
[68]
GSM105137
[69]
GSM105138
sample_count
70
group_sizes
null
group_sizes_basis
null
platform
97;96
taxon
Homo sapiens
title
Variations in gene expression among different types of human skeletal muscle
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[8] object · 15 fields
id
data:geo:GSE47881
role
raw
format
geo-series
media_type
application/vnd.ncbi.geo-series+json
uri
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE47881
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE47881
version
null
note
The datasets presented in this study can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo/).
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The datasets presented in this study can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo/).
access_statement_kind
data_availability_statement
sample_accessions array · 89 items
[0]
GSM1161771
[1]
GSM1161772
[2]
GSM1161773
[3]
GSM1161774
[4]
GSM1161775
[5]
GSM1161776
[6]
GSM1161777
[7]
GSM1161778
[8]
GSM1161779
[9]
GSM1161780
[10]
GSM1161781
[11]
GSM1161782
[12]
GSM1161783
[13]
GSM1161784
[14]
GSM1161785
[15]
GSM1161786
[16]
GSM1161787
[17]
GSM1161788
[18]
GSM1161789
[19]
GSM1161790
[20]
GSM1161791
[21]
GSM1161792
[22]
GSM1161793
[23]
GSM1161794
[24]
GSM1161795
[25]
GSM1161796
[26]
GSM1161797
[27]
GSM1161798
[28]
GSM1161799
[29]
GSM1161800
[30]
GSM1161801
[31]
GSM1161802
[32]
GSM1161803
[33]
GSM1161804
[34]
GSM1161805
[35]
GSM1161806
[36]
GSM1161807
[37]
GSM1161808
[38]
GSM1161809
[39]
GSM1161810
[40]
GSM1161811
[41]
GSM1161812
[42]
GSM1161813
[43]
GSM1161814
[44]
GSM1161815
[45]
GSM1161816
[46]
GSM1161817
[47]
GSM1161818
[48]
GSM1161819
[49]
GSM1161820
[50]
GSM1161821
[51]
GSM1161822
[52]
GSM1161823
[53]
GSM1161824
[54]
GSM1161825
[55]
GSM1161826
[56]
GSM1161827
[57]
GSM1161828
[58]
GSM1161829
[59]
GSM1161830
[60]
GSM1161831
[61]
GSM1161832
[62]
GSM1161833
[63]
GSM1161834
[64]
GSM1161835
[65]
GSM1161836
[66]
GSM1161837
[67]
GSM1161838
[68]
GSM1161839
[69]
GSM1161840
[70]
GSM1161841
[71]
GSM1161842
[72]
GSM1161843
[73]
GSM1161844
[74]
GSM1161845
[75]
GSM1161846
[76]
GSM1161847
[77]
GSM1161848
[78]
GSM1161849
[79]
GSM1161850
[80]
GSM1161851
[81]
GSM1161852
[82]
GSM1161853
[83]
GSM1161854
[84]
GSM1161855
[85]
GSM1161856
[86]
GSM1161857
[87]
GSM1161858
[88]
GSM1161859
sample_count
89
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
DERBY BBSRC RET Study: Impact of resistance exercise on human skeletal muscle gene expression
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[9] object · 15 fields
id
data:geo:GSE5086
role
raw
format
geo-series
media_type
application/vnd.ncbi.geo-series+json
uri
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE5086
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE5086
version
null
note
The datasets presented in this study can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo/).
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The datasets presented in this study can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo/).
access_statement_kind
data_availability_statement
sample_accessions array · 81 items
[0]
GSM114642
[1]
GSM114643
[2]
GSM114644
[3]
GSM114645
[4]
GSM114646
[5]
GSM114647
[6]
GSM114648
[7]
GSM114649
[8]
GSM114650
[9]
GSM114651
[10]
GSM114652
[11]
GSM114653
[12]
GSM114654
[13]
GSM114655
[14]
GSM114656
[15]
GSM114657
[16]
GSM114658
[17]
GSM114659
[18]
GSM114660
[19]
GSM114661
[20]
GSM114662
[21]
GSM114663
[22]
GSM114664
[23]
GSM114665
[24]
GSM114666
[25]
GSM114667
[26]
GSM114668
[27]
GSM114669
[28]
GSM114670
[29]
GSM114671
[30]
GSM114672
[31]
GSM114673
[32]
GSM114674
[33]
GSM114675
[34]
GSM114676
[35]
GSM114677
[36]
GSM114678
[37]
GSM114679
[38]
GSM114680
[39]
GSM114681
[40]
GSM114682
[41]
GSM114683
[42]
GSM114684
[43]
GSM114685
[44]
GSM114686
[45]
GSM114687
[46]
GSM114688
[47]
GSM114689
[48]
GSM114690
[49]
GSM114691
[50]
GSM114692
[51]
GSM114693
[52]
GSM114694
[53]
GSM114695
[54]
GSM114696
[55]
GSM114697
[56]
GSM114698
[57]
GSM114699
[58]
GSM114700
[59]
GSM114701
[60]
GSM114702
[61]
GSM114703
[62]
GSM114704
[63]
GSM114705
[64]
GSM114706
[65]
GSM114707
[66]
GSM114708
[67]
GSM114709
[68]
GSM114710
[69]
GSM114711
[70]
GSM114712
[71]
GSM114713
[72]
GSM114714
[73]
GSM114715
[74]
GSM114716
[75]
GSM114717
[76]
GSM114718
[77]
GSM114719
[78]
GSM114720
[79]
GSM114721
[80]
GSM114722
sample_count
81
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Transcriptional profile of aging human muscle
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[10] object · 15 fields
id
data:geo:GSE674
role
raw
format
geo-series
media_type
application/vnd.ncbi.geo-series+json
uri
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE674
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE674
version
null
note
The datasets presented in this study can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo/).
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The datasets presented in this study can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo/).
access_statement_kind
data_availability_statement
sample_accessions array · 30 items
[0]
GSM10354
[1]
GSM10355
[2]
GSM10356
[3]
GSM10359
[4]
GSM10360
[5]
GSM10361
[6]
GSM10362
[7]
GSM10363
[8]
GSM10364
[9]
GSM10365
[10]
GSM10366
[11]
GSM10367
[12]
GSM10368
[13]
GSM10369
[14]
GSM10370
[15]
GSM10374
[16]
GSM10375
[17]
GSM10376
[18]
GSM10377
[19]
GSM10378
[20]
GSM10379
[21]
GSM10380
[22]
GSM10381
[23]
GSM10382
[24]
GSM10383
[25]
GSM10384
[26]
GSM10385
[27]
GSM10386
[28]
GSM10387
[29]
GSM10388
sample_count
30
group_sizes
null
group_sizes_basis
null
platform
97;96
taxon
Homo sapiens
title
Normal Muscle - Female , Effect of Age
resolution_checked_at
2026-11-01T15:39:55Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[11] object · 15 fields
id
data:geo:GSE9013
role
raw
format
geo-series
media_type
application/vnd.ncbi.geo-series+json
uri
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE9013
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE9013
version
null
note
The datasets presented in this study can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo/).
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The datasets presented in this study can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo/).
access_statement_kind
data_availability_statement
sample_accessions array · 12 items
[0]
GSM228795
[1]
GSM228796
[2]
GSM228797
[3]
GSM228798
[4]
GSM228799
[5]
GSM228800
[6]
GSM228801
[7]
GSM228802
[8]
GSM228803
[9]
GSM228804
[10]
GSM228805
[11]
GSM228806
sample_count
12
group_sizes
null
group_sizes_basis
null
platform
1261
taxon
Mus musculus
title
Expression data from side-population sorted putative intestinal stem cells.
resolution_checked_at
2026-11-01T15:39:55Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
gaps array · 22 items
[0]
asset:data:geo:GSE118825 not downloaded
[1]
asset:data:geo:GSE118825 licence not read
[2]
asset:data:geo:GSE25941 not downloaded
[3]
asset:data:geo:GSE25941 licence not read
[4]
asset:data:geo:GSE28392 not downloaded
[5]
asset:data:geo:GSE28392 licence not read
[6]
asset:data:geo:GSE28422 not downloaded
[7]
asset:data:geo:GSE28422 licence not read
[8]
asset:data:geo:GSE362 not downloaded
[9]
asset:data:geo:GSE362 licence not read
[10]
asset:data:geo:GSE38718 not downloaded
[11]
asset:data:geo:GSE38718 licence not read
[12]
asset:data:geo:GSE4667 not downloaded
[13]
asset:data:geo:GSE4667 licence not read
[14]
asset:data:geo:GSE47881 not downloaded
[15]
asset:data:geo:GSE47881 licence not read
[16]
asset:data:geo:GSE5086 not downloaded
[17]
asset:data:geo:GSE5086 licence not read
[18]
asset:data:geo:GSE674 not downloaded
[19]
asset:data:geo:GSE674 licence not read
[20]
asset:data:geo:GSE9013 not downloaded
[21]
asset:data:geo:GSE9013 licence not read
analysis object · 4 fields
state
complete
methods array · 2 items
[0] object · 10 fields
id
method-1
family
correlation_analysis
specific
pearson
label
Correlation analysis
dsl_operations array · 1 item
[0]
pearson_r
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
paired_numeric_columns
evidence object · 3 fields
score
1
band
verbatim
quote
The relationships between ages and gene expressions in the GSE47881 and GSE118825 datasets were performed by Pearson correlation analysis and linear analysis.
[1] object · 10 fields
id
method-2
family
network_analysis
specific
ppi_network
label
Network / pathway analysis
dsl_operations array · 3 items
[0]
build_graph
[1]
centrality_scores
[2]
pathway_enrich
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
edge_list
evidence object · 3 fields
score
0.7
band
medium
quote
protein-protein interaction
targets array · 0 items
gaps array · 0 items
capability object · 3 fields
state
complete
requirements array · 1 item
[0] object · 6 fields
capability_id
capability:computational_analysis
label
Computational analysis platform
assay_families array · 9 items
[0]
meta_analysis
[1]
machine_learning
[2]
survival_analysis
[3]
statistical_regression
[4]
pca
[5]
molecular_docking
[6]
network_analysis
[7]
differential_expression
[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
gaps array · 0 items
readiness object · 8 fields
state
complete
tier
R1
blocked_on
nothing:replicable_now
axes object · 3 fields
method object · 5 fields
tier
R1
expressible
true
required_operations array · 1 item
[0]
pearson_r
missing_operations array · 0 items
basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: pearson.
capability object · 4 fields
tier
R1
capability_id
capability:computational_analysis
availability_state
owned
basis
The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
data object · 6 fields
tier
R1
reachable
true
accessions array · 11 items
[0]
GSE47881
[1]
GSE118825
[2]
GSE25941
[3]
GSE28392
[4]
GSE28422
[5]
GSE362
[6]
GSE38718
[7]
GSE5086
[8]
GSE674
[9]
GSE9013
[10]
GSE4667
resolved_accessions array · 11 items
[0]
GSE47881
[1]
GSE118825
[2]
GSE25941
[3]
GSE28392
[4]
GSE28422
[5]
GSE362
[6]
GSE38718
[7]
GSE5086
[8]
GSE674
[9]
GSE9013
[10]
GSE4667
statements array · 1 item
[0]
The datasets presented in this study can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo/).
basis
The paper names GSE47881, GSE118825, GSE25941, GSE28392, GSE28422, GSE362, GSE38718, GSE5086, GSE674, GSE9013, GSE4667 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
can_run object · 3 fields
dsl_operations array · 1 item
[0]
pearson_r
assets array · 2 items
[0]
source:pmid:34229541
[1]
data:geo:GSE118825
steps array · 1 item
[0]
run_analysis
must_build object · 5 fields
dsl_operations array · 0 items
converters array · 0 items
readers array · 0 items
capabilities array · 0 items
data_gaps array · 1 item
[0]
data:geo:GSE118825
gaps array · 0 items
review object · 5 fields
state
partial
machine_critique object · 5 fields
kind
extraction_review
reader object · 5 fields
model
MiniMax-M3.1-Flash
provider
minimax
provider_family
minimax
read_at
2026-10-31T18:31:55Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
3
usage object · 3 fields
prompt_tokens
22730
completion_tokens
2330
cached_tokens
784
stages array · 1 item
[0] object · 4 fields
id
extraction
state
complete
reader
MiniMax-M3.1-Flash
provider
minimax
gaps array · 3 items
[0]
review.independent_reader
[1]
review.machine_critique
[2]
review.human_critique
execution object · 5 fields
state
absent
status
not_run
mode
null
runs array · 0 items
gaps array · 1 item
[0]
execution.not_run
provenance object · 7 fields
entities array · 3 items
[0] object · 3 fields
id
pmid:34229541
type
paper
label
pmid:34229541
[1] object · 3 fields
id
source:pmid:34229541
type
manuscript
label
PMID 34229541 full text
[2] object · 3 fields
id
data:geo:GSE118825
type
dataset
label
GEO GSE118825
activities array · 3 items
[0] object · 4 fields
id
activity-reading-sci-2026-11-01
type
classification
used array · 3 items
[0] object · 3 fields
id
pmid:34229541
type
paper
label
pmid:34229541
[1] object · 3 fields
id
source:pmid:34229541
type
manuscript
label
PMID 34229541 full text
[2] object · 3 fields
id
data:geo:GSE118825
type
dataset
label
GEO GSE118825
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-34229541
type
extraction
used array · 1 item
[0]
source:pmid:34229541
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE118825
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE118825
agent
agent:corpus-assay-engine
agents array · 2 items
[0] object · 3 fields
id
agent:corpus-assay-engine
type
software
label
Corpus assay engine
[1] object · 3 fields
id
agent:minimax-reader
type
software
label
MiniMax literature reader
source_run_id
reading-sci-2026-11-01
dsl_catalogue_fingerprint
343fb30756ba6ec3
capability_table_fingerprint
2cb3e42f047d2ecf
snapshot_id
ba34b49490d9bfaf
lineage object · 4 fields
parent_id
pmid:34229541
parent_hash
sha256:3a8c6e6fd88b8d0e7bce0b2ab6637ae819224c0ba5e88f9b53643c4899cda089
fork_of
null
gaps array · 26 items
[0]
asset:data:geo:GSE118825 licence not read
[1]
asset:data:geo:GSE118825 not downloaded
[2]
asset:data:geo:GSE25941 licence not read
[3]
asset:data:geo:GSE25941 not downloaded
[4]
asset:data:geo:GSE28392 licence not read
[5]
asset:data:geo:GSE28392 not downloaded
[6]
asset:data:geo:GSE28422 licence not read
[7]
asset:data:geo:GSE28422 not downloaded
[8]
asset:data:geo:GSE362 licence not read
[9]
asset:data:geo:GSE362 not downloaded
[10]
asset:data:geo:GSE38718 licence not read
[11]
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review.human_critique
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review.machine_critique
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ally obtained and verified with quantitative real-time PCR (qRT-PCR). The results showed that the expre
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The relationships between ages and gene expressions in the GSE47881 and GSE118825 datasets were performed by Pearson correlation analysis and linear analysis.
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34229541", "kind": "science-record", "revision": 7, "content_hash": "sha256:f69f179e56f05002f91bad8b9759ef9200a7e99a93a370ac683597fb51ad825e", "created_at": "2026-11-01T15:41:42Z", "updated_at": "2026-11-01T22:04:08Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Declined expressions of vast mitochondria-related genes represented by CYCS and transcription factor ESRRA in skeletal muscle aging.", "doi": "10.1080/21655979.2021.1948951", "pmid": "34229541", "authors": ["Jingbao Kan", "Yifang Hu", "Yaoqi Ge", "WenSong Zhang", "Shan Lu", "Cuiping Zhao", "Rihua Zhang", "Yun Liu"], "journal": "Bioengineered", "year": 2021, "abstract": "Age-related skeletal muscle deterioration (sarcopenia) has a significant effect on the elderly's health and quality of life, but the molecular and gene regulatory mechanisms remain largely unknown. It is necessary to identify the candidate genes related to skeletal muscle aging and prospective therapeutic targets for effective treatments. The age-line-related genes (ALRGs) and age-line-related transcripts (ALRTs) were investigated using the gene expression profiles of GSE47881 and GSE118825 from the Gene Expression Omnibus (GEO) database. The protein-protein interaction (PPI) networks were performed to identify the key molecules with Cytoscape, and Gene Set Enrichment Analysis (GSEA) was used to clarify the potential molecular functions. Two hub molecules were finally obtained and verified with quantitative real-time PCR (qRT-PCR). The results showed that the expression of mitochondria genes involved in mitochondrial electron transport, complex assembly of the respiratory chain, tricarboxylic acid cycle, oxidative phosphorylation, and ATP synthesis were down-regulated in skeletal muscle with aging. We further identified a primary hub gene of CYCS (Cytochrome C) and a key transcription factor of ESRRA (Estrogen-related Receptor Alpha) to be associated closely with skeletal muscle aging. PCR analysis confirmed the expressions of CYCS and ESRRA in gastrocnemius muscles of mice of different ages were significantly different, and decreased gradually with age. In conclusion, the main cause of skeletal muscle aging may be the systematically reduced expression of mitochondrial functional genes. 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