Objective
The reduced ability of skeletal muscle to grow, termed anabolic resistance (AR), is thought to be a major cause of age-associated muscle loss (sarcopenia). At the cellular level, AR is caused by an impaired activation of the protein kinase mTORC1, which in turn blunts protein synthetic responses to anabolic stimuli. Lysosomal trafficking is critical for the full activation of mTORC1, with the blocking of this event creating anabolic resistance in otherwise healthy cells. However, to date, this phenomenon has not been examined in human skeletal muscle. Therefore, our working hypothesis is that alterations in lysosomal trafficking may be an underlying mechanism to explain impaired mTORC1 activity and AR in elderly individuals. To address this hypothesis, we will define, for the first time, the role and regulation of lysosomal trafficking in age-associated AR in human skeletal muscle.
Through a combination of in-vitro and in vivo studies we will examine (1) whether genetic induction of lysosomal trafficking can activate mTORC1 and overcome chemical/nutrient induced AR in human primary myotubes, (2) whether genetic knockdown of proteins that stimulate lysosomal trafficking can inhibit mTORC1 activity and cause AR, and (3) examine whether lysosomal trafficking differs between young and elderly subjects, in vivo, in response to anabolic stimuli such as amino acids and resistance exercise.
The importance of this work should not be understated, given that the number of individuals aged over 60 and 80 years is expected to triple and quadruple respectively by 2050. By advancing the understanding of why elderly individuals exhibit AR and how this phenomenon may contribute to the development of sarcopenia, the work proposed herein has great potential for the development of novel therapeutic approaches to prevent or reduce the occurrence of AR, reduce the severity of sarcopenia which in turn will dramatically improve quality of life.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine endocrinology diabetes
- medical and health sciences clinical medicine oncology
- natural sciences chemical sciences organic chemistry amines
- medical and health sciences health sciences nutrition obesity
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
-
H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
See all projects funded under this programme -
H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
See all projects funded under this programme
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MSCA-IF-EF-ST - Standard EF
See all projects funded under this funding scheme
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2015
See all projects funded under this callCoordinator
Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
B15 2TT Birmingham
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.