Evidence map›Paper›PMID 33244887›Full record

ArticleJournal of cachexia, sarcopenia and muscle2021

The hypothalamic-pituitary-gonadal axis controls muscle stem cell senescence through autophagosome clearance.

Ji-Hoon Kim, Inkuk Park, Hijai R Shin, Joonwoo Rhee, Ji-Yun Seo, Young-Woo Jo, Kyusang Yoo, Sang-Hyeon Hann, Jong-Seol Kang, Jieon Park and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of cachexia, sarcopenia and muscle, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.3field-weighted citation impact, top 42% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 15 citations in OpenAlex.

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  11. Autophagy in muscle regeneration: potential therapies for myopathies.Journal of cachexia, sarcopenia and muscle · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 2 countries.

Ji-Hoon KimSchool of Biological Sciences, Seoul National University, Seoul, South Korea.
Inkuk ParkSchool of Biological Sciences, Seoul National University, Seoul, South Korea.
Hijai R ShinDepartment of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
Joonwoo RheeSchool of Biological Sciences, Seoul National University, Seoul, South Korea.
Ji-Yun SeoSchool of Biological Sciences, Seoul National University, Seoul, South Korea.
Young-Woo JoSchool of Biological Sciences, Seoul National University, Seoul, South Korea.
Kyusang YooSchool of Biological Sciences, Seoul National University, Seoul, South Korea.
Sang-Hyeon HannSchool of Biological Sciences, Seoul National University, Seoul, South Korea.
Jong-Seol KangSchool of Biological Sciences, Seoul National University, Seoul, South Korea.
Jieon ParkSchool of Biological Sciences, Seoul National University, Seoul, South Korea.
Ye Lynne KimSchool of Biological Sciences, Seoul National University, Seoul, South Korea.
Ju-Yeon MoonCollege of Pharmacy, The Catholic University of Korea, Gyeonggi-do, South Korea.
Man Ho ChoiMolecular Recognition Research Center, KIST, Seoul, South Korea.
Young-Yun KongSchool of Biological Sciences, Seoul National University, Seoul, South Korea.
Seoul National University · KRCatholic University of Korea · KRInstitute on Aging · USKorea Pharma (South Korea) · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundWith organismal aging, the hypothalamic-pituitary-gonadal (HPG) activity gradually decreases, resulting in the systemic functional declines of the target tissues including skeletal muscles. Although the HPG axis plays an important role in health span, how the HPG axis systemically prevents functional aging is largely unknown.

methodsWe generated muscle stem cell (MuSC)-specific androgen receptor (Ar) and oestrogen receptor 2 (Esr2) double knockout (dKO) mice and pharmacologically inhibited (Antide) the HPG axis to mimic decreased serum levels of sex steroid hormones in aged mice. After short-term and long-term sex hormone signalling ablation, the MuSCs were functionally analysed, and their aging phenotypes were compared with those of geriatric mice (30-month-old). To investigate pathways associated with sex hormone signalling disruption, RNA sequencing and bioinformatic analyses were performed.

resultsDisrupting the HPG axis results in impaired muscle regeneration [wild-type (WT) vs. dKO, P < 0.0001; Veh vs. Antide, P = 0.004]. The expression of DNA damage marker (in WT = 7.0 ± 1.6%, dKO = 32.5 ± 2.6%, P < 0.01; in Veh = 13.4 ± 4.5%, Antide = 29.7 ± 5.5%, P = 0.028) and senescence-associated β-galactosidase activity (in WT = 3.8 ± 1.2%, dKO = 10.3 ± 1.6%, P < 0.01; in Veh = 2.1 ± 0.4%, Antide = 9.6 ± 0.8%, P = 0.005), as well as the expression levels of senescence-associated genes, p16

conclusionsOur data show that the HPG axis systemically controls autophagosome clearance in MuSCs through Tfeb and prevents MuSCs from senescence, suggesting that sustained HPG activity throughout life regulates autophagosome clearance to maintain the quiescence of MuSCs by preventing senescence until advanced age.

Indexed as

AutophagosomesMyoblastsStem CellsAnimalsCellular SenescenceGonadsHypothalamusMiceMuscle, SkeletalPituitary GlandRegenerationAgingAutophagyCellular senescenceMuscle regenerationMuscle stem cellSex steroid hormones

Identifiers

PMID33244887
PMCPMC7890269
OpenAlexW3107762314

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.