Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Tp53inp2-Dependent Activation of Muscle Autophagy Ameliorates Sarcopenia and Promotes Healthy Aging Publisher Pubmed



Sebastian D1, 2, 3 ; Beltra M2, 3, 4 ; Irazoki A2, 3, 4 ; Sala D2, 3, 4 ; Aparicio P5 ; Aris C6 ; Alibakhshi E7, 8, 9 ; Rubiovalera M10, 11 ; Palacin M2, 4, 12 ; Castellanos J5 ; Lores L7 ; Zorzano A2, 3, 4
Authors
Show Affiliations
Authors Affiliations
  1. 1. Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain
  2. 2. Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain
  3. 3. Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain
  4. 4. Departament de Bioquimica i Biomedicina Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain
  5. 5. Department of Orthopedic Surgery and Traumatology, Hospital de Sant Boi Sant Joan de Deu, Barcelona, Sant Boi de Llobregat, Spain
  6. 6. Department of Family and Community Medicine, Hospital de Sant Boi Sant Joan de Deu, Barcelona, Sant Boi de Llobregat, Spain
  7. 7. Pneumology Department, Hospital de Sant Boi Sant Joan de Deu, Barcelona, Sant Boi de Llobregat, Spain
  8. 8. Physical Medicine and Rehabilitation Department, Clinical Research Development Unit, Baqyiatallah Hospital, Faculty of Medicine, Baqyiatallah University of Medical Science, Tehran, Iran
  9. 9. Quantitative MR Imaging and Spectroscopy Group, Research Center for Molecular and Cellular Imaging, Advanced Medical Technologies and Equipment Institute, Tehran University of Medical Science, Tehran, Iran
  10. 10. Quality and Patient Safety Unit, Hospital de Sant Boi Sant Joan de Deu, Barcelona, Sant Boi de Llobregat, Spain
  11. 11. Centro de Investigacion Biomedica en Epidemiologia y Salud Publica (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain
  12. 12. Centro de Investigacion Biomedica de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain

Source: Autophagy Published:2024


Abstract

Sarcopenia is a major contributor to disability in older adults, and thus, it is key to elucidate the mechanisms underlying its development. Increasing evidence suggests that impaired macroautophagy/autophagy contributes to the development of sarcopenia. However, the mechanisms leading to reduced autophagy during aging remain largely unexplored, and whether autophagy activation protects from sarcopenia has not been fully addressed. Here we show that the autophagy regulator TP53INP2/TRP53INP2 is decreased during aging in mouse and human skeletal muscle. Importantly, chronic activation of autophagy by muscle-specific overexpression of TRP53INP2 prevents sarcopenia and the decline of muscle function in mice. Acute re-expression of TRP53INP2 in aged mice also improves muscle atrophy, enhances mitophagy, and reduces ROS production. In humans, high levels of TP53INP2 in muscle are associated with increased muscle strength and healthy aging. Our findings highlight the relevance of an active muscle autophagy in the maintenance of muscle mass and prevention of sarcopenia. Abbreviation: ATG7: autophagy related 7; BMI: body mass index; EIF4EBP1: eukaryotic translation initiation factor 4E binding protein 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; ROS: reactive oxygen species; TP53INP2: tumor protein p53 inducible nuclear protein 2; WT: wild type. © 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.