2026-04-28T22:57:03Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/92462024-10-31T11:42:20Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Segales, Jessica
author
Perdiguero, Eusebio
author
Serrano, Antonio L
author
Sousa-Victor, Pedro
author
Ortet, Laura
author
Jardí, Mercè
author
Budanov, Andrei V
author
Garcia-Prat, Laura
author
Sandri, Marco
author
Thomson, David M
author
Karin, Michael
author
Hee Lee, Jun
author
Munoz-Canoves, Pura
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Fundación La Caixa
funder
Instituto de Salud Carlos III
funder
Fundación ProCNIC
funder
Ellision Medical Foundation
funder
Russian Science Foundation
2020-03-09T13:29:43Z
2020-03-09T13:29:43Z
2020-01
Nat Commun. 2020; 11(1):189
2041-1723
http://hdl.handle.net/20.500.12105/9246
31929511
10.1038/s41467-019-13832-9
2041-1723
Nature communications
A unique property of skeletal muscle is its ability to adapt its mass to changes in activity. Inactivity, as in disuse or aging, causes atrophy, the loss of muscle mass and strength, leading to physical incapacity and poor quality of life. Here, through a combination of transcriptomics and transgenesis, we identify sestrins, a family of stress-inducible metabolic regulators, as protective factors against muscle wasting. Sestrin expression decreases during inactivity and its genetic deficiency exacerbates muscle wasting; conversely, sestrin overexpression suffices to prevent atrophy. This protection occurs through mTORC1 inhibition, which upregulates autophagy, and AKT activation, which in turn inhibits FoxO-regulated ubiquitin-proteasome-mediated proteolysis. This study reveals sestrin as a central integrator of anabolic and degradative pathways preventing muscle wasting. Since sestrin also protected muscles against aging-induced atrophy, our findings have implications for sarcopenia.
eng
Sestrin prevents atrophy of disused and aging muscles by integrating anabolic and catabolic signals
journal article
TElDRU5DSUEgREUgRElTVFJJQlVDScOTTiBOTyBFWENMVVNJVkEKCkFjZXB0YW5kbyBlc3RhIGxpY2VuY2lhLCBVc3RlZCAoZWwgYXV0b3IvZXMgbyBlbCBwcm9waWV0YXJpby9zIGRlIGxvcyBkZXJlY2hvcyBkZSAKYXV0b3IpIGNvbmNlZGUgYSBSRVBJU0FMVUQgZWwgZGVyZWNobyBubyBleGNsdXNpdm8gZGUgcmVwcm9kdWNpciwgY29udmVydGlyLCB5L28gCmRpc3RyaWJ1aXIgc3UgZG9jdW1lbnRvIChpbmNsdXllbmRvIHN1IHJlc3VtZW4pIGEgbml2ZWwgbXVuZGlhbCBlbiBmb3JtYXRvIGRpZ2l0YWwsIAppbmNsdXllbmRvLCBhdWRpbyB5IHbDrWRlbywgYSB0cmF2w6lzIGRlIHN1IHJlcG9zaXRvcmlvIGluc3RpdHVjaW9uYWwuCgpVc3RlZCBhY2VwdGEgcXVlIFJFUElTQUxVRCBwdWVkZSwgc2luIGFsdGVyYXIgc3UgY29udGVuaWRvLCBjb252ZXJ0aXIgc3UgZG9jdW1lbnRvIAphIGN1YWxxdWllciBvdHJvIGZvcm1hdG8gZGlnaXRhbCBkZSBkYXRvcywgYXVkaW8geSB2aWRlbywgY29uIGVsIHByb3DDs3NpdG8gZGUgcXVlIApwdWVkYSBzZXIgYWxvamFkbyBlbiBlbCByZXBvc2l0b3Jpby4gCgpVc3RlZCBlc3TDoSBkZSBhY3VlcmRvIGNvbiBxdWUgUkVQSVNBTFVEIHB1ZWRhIGNvbnNlcnZhciBtw6FzIGRlIHVuYSBjb3BpYSBkZSBlc3RlIApkb2N1bWVudG8gcGFyYSBhc2VndXJhciBzdSBzZWd1cmlkYWQsIHByZXNlcnZhY2nDs24geSBhY2Nlc28uCgpVc3RlZCBkZWNsYXJhIHF1ZSBlbCBkb2N1bWVudG8gZXMgdW4gdHJhYmFqbyBvcmlnaW5hbCwgeSBxdWUgdGllbmUgZWwgZGVyZWNobyBkZSAKb3RvcmdhciBsb3MgZGVyZWNob3MgY29udGVuaWRvcyBlbiBlc3RhIGxpY2VuY2lhLiBUYW1iacOpbiBkZWNsYXJhIHF1ZSBzdSBwZXRpY2nDs24gCm5vIGluZnJpbmdlIGxvcyBkZXJlY2hvcyBkZSBhdXRvciBkZSBuYWRpZS4gCgpTaSBlbCBkb2N1bWVudG8gY29udGllbmUgbWF0ZXJpYWxlcyBwYXJhIGxvcyBxdWUgbm8gc2UgdGllbmVuIGxvcyBkZXJlY2hvcyBkZSBhdXRvciwgClVzdGVkIGRlY2xhcmEgcXVlIGhhIG9idGVuaWRvIGVsIHBlcm1pc28gc2luIHJlc3RyaWNjacOzbiBkZWwgcHJvcGlldGFyaW8gZGUgbG9zIApkZXJlY2hvcyB5IHF1ZSBlbiBkaWNobyBtYXRlcmlhbCwgZXN0w6EgY2xhcmFtZW50ZSBpZGVudGlmaWNhZGEgeSByZWNvbm9jaWRhIHN1IAphdXRvcsOtYSBkZW50cm8gZWwgdGV4dG8gbyBkZWwgY29udGVuaWRvIGRlIGRpY2hvIGRvY3VtZW50by4gCgpTaSBlbCBlbnbDrW8gc2UgYmFzYSBlbiB1biB0cmFiYWpvIHF1ZSBoYSBzaWRvIHBhdHJvY2luYWRvIG8gYXBveWFkbyBwb3IgdW5hIGFnZW5jaWEgCnUgb3JnYW5pemFjacOzbiBkaXN0aW50YSBhIFJFUElTQUxVRCwgdXN0ZWQgYWNlcHRhIHF1ZSBoYSBjdW1wbGlkbyBjb24gZWwgZGVyZWNobyBkZSAKcmV2aXNpw7NuIHkgb3RyYXMgb2JsaWdhY2lvbmVzIHJlcXVlcmlkYXMgcG9yIGNvbnRyYXRvIG8gYWN1ZXJkby4gCgpSRVBJU0FMVUQgaWRlbnRpZmljYXLDoSBjbGFyYW1lbnRlIHN1KHMpIG5vbWJyZShzKSBjb21vIGF1dG9yKHMpIG8gcHJvcGlldGFyaW8ocykgCmRlbCBkb2N1bWVudG8sIHkgbm8gaGFyw6EgbmluZ3VuYSBhbHRlcmFjacOzbiwgZXhjZXB0byBzZWfDum4gbG8gcGVybWl0aWRvIHBvciBlc3RhIApsaWNlbmNpYS4gCg==
URL
https://repisalud.isciii.es/bitstreams/93b5123b-caa9-4868-b486-247ada7360f3/download
File
MD5
b735a08f4ebfc1f1588e375f08e58cf6
1594027
application/pdf
SestrinPreventsAtrophyDisused_2020.pdf
URL
https://repisalud.isciii.es/bitstreams/1d673597-af09-4b85-8506-e063b005f8ce/download
File
MD5
f5e43a8a4d40e45adfe9ed5ddf5d6b71
9474126
application/pdf
SestrinPreventsAtrophyDisused_2020_MOESM1_ESM.pdf
URL
https://repisalud.isciii.es/bitstreams/03f9454c-c419-46ca-9c71-6b58cfbe138c/download
File
MD5
07f1eb9d8f488f37597493ca9e105916
2309139
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
SestrinPreventsAtrophyDisused_2020_MOESM2_ESM.xlsx
URL
https://repisalud.isciii.es/bitstreams/02217136-c5a8-427c-ad7c-ea21db68470d/download
File
MD5
543073239f10d26356f4d67fad44fea1
25005
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
SestrinPreventsAtrophyDisused_2020_MOESM3_ESM.xlsx
URL
https://repisalud.isciii.es/bitstreams/afa9ace7-4f3c-4b10-99aa-ca6680de46a4/download
File
MD5
1309be5ab59f3785ed4905c9ab10e657
12848
application/vnd.openxmlformats-officedocument.wordprocessingml.document
SestrinPreventsAtrophyDisused_2020_MOESM5_ESM.docx
URL
https://repisalud.isciii.es/bitstreams/1dc60c42-3564-43b0-8706-0c2b6b37460a/download
File
MD5
5dc79f1a24d7709260c00817260afb0f
17367672
application/vnd.openxmlformats-officedocument.spreadsheetml.sheet
SestrinPreventsAtrophyDisused_2020_MOESM6_ESM.xlsx
URL
https://repisalud.isciii.es/bitstreams/aa4c7908-5c02-46d8-8293-3ff01af863e0/download
File
MD5
13fef7ec27de8975ba107d72cbfaad7a
75972
text/plain
SestrinPreventsAtrophyDisused_2020.pdf.txt
URL
https://repisalud.isciii.es/bitstreams/e59c843e-936f-4713-845c-bea7bc0387bf/download
File
MD5
cab5482680c3b835560a3b3174237f98
17146
text/plain
SestrinPreventsAtrophyDisused_2020_MOESM1_ESM.pdf.txt
URL
https://repisalud.isciii.es/bitstreams/f7b0f8d2-f7d0-4d56-9b83-3a12c4e9ab22/download
File
MD5
89857a6a1a525241e8ecc0438c0aadf9
100000
text/plain
SestrinPreventsAtrophyDisused_2020_MOESM2_ESM.xlsx.txt
URL
https://repisalud.isciii.es/bitstreams/ac28f0e9-fde2-4b47-bc85-346e8c14dac5/download
File
MD5
5c6b92eca51cd875cde4327ab5859c7e
12513
text/plain
SestrinPreventsAtrophyDisused_2020_MOESM3_ESM.xlsx.txt
URL
https://repisalud.isciii.es/bitstreams/57501789-848b-4343-9f2d-1fa24bd7efa8/download
File
MD5
dd859c56ba834beb4bf729628c506687
458
text/plain
SestrinPreventsAtrophyDisused_2020_MOESM5_ESM.docx.txt
URL
https://repisalud.isciii.es/bitstreams/6bd72a79-bf2b-4e5e-ab17-023f2b248b32/download
File
MD5
1c6a277df0ec96f6c4fbe9613d42e6d7
54980
text/plain
SestrinPreventsAtrophyDisused_2020_MOESM6_ESM.xlsx.txt