Involvement of Muscle Mitochondrial Dysfunction in Frailty in Older Adults. Role of Exercise

NCT07828847 | Recruiting

• 1 other identifier: MITOSTRENGTH
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to investigate the role of skeletal muscle mitochondrial dysfunction in the development of frailty in older adults and to evaluate whether a short-term, supervised resistance training intervention can improve skeletal muscle health and physical function. Frailty is a common age-related condition associated with increased vulnerability to disability, hospitalisation, and loss of independence. It is characterised by features that may include weakness, fatigue, reduced physical activity, and slower walking speed. Mitochondrial dysfunction in skeletal muscle may contribute to the development of frailty and may be further influenced by chronic conditions such as type 2 diabetes mellitus (T2DM), which are associated with metabolic alterations, inflammation, oxidative stress, and insulin resistance. Resistance training is an effective strategy to counteract age-related declines in muscle strength and physical function. However, the cellular and molecular mechanisms linking resistance training to improvements in mitochondrial function, skeletal muscle health, and resilience in older adults remain incompletely understood. The study will include approximately 120 participants comprising older adults with T2DM, healthy older adults, and young healthy controls. All participants will complete a 6-week supervised resistance training intervention, consisting of two sessions per week. Assessments performed before and after the intervention will include body composition, muscle morphology, physical performance, muscle strength, frailty, and blood-based biomarkers. Peripheral blood mononuclear cells (PBMCs) will be used to assess mitochondrial function, and plasma samples will be used for proteomic profiling. Stool samples will be collected for analysis of gut microbiota. A subset of participants will undergo skeletal muscle biopsies of the vastus lateralis at baseline and after the intervention. Muscle samples will be used to assess mitochondrial oxidative phosphorylation capacity, mitochondrial quality-control proteins, muscle fibre morphology, cell-type-specific transcriptomic profiles using single-nucleus RNA sequencing, and chromatin accessibility using ATAC-seq. The study will provide an integrated assessment of the effects of resistance training on mitochondrial function, skeletal muscle biology, physical function, frailty, circulating biomarkers, and gut microbiota. These findings may help clarify the biological mechanisms through which resistance training influences muscle health and resilience during ageing and in older adults with T2DM.

Conditions

Diabetes Type 2; Frail Elderly Syndrome; Functionality; Mitochondrial Function, Bioenergetics

Keywords

Diabetes type 2; Frailty; Mitochondrial function; Skeletal Muscle; Physical Function

Outcome Measures

Primary Outcomes (2)

• Change in Mitochondrial Oxidative Phosphorylation (OXPHOS) Capacity in Skeletal Muscle

  Mitochondrial oxidative phosphorylation capacity will be assessed in permeabilised skeletal muscle fibre bundles obtained from vastus lateralis biopsies using high-resolution respirometry (Oxygraph-2k, Oroboros Instruments). OXPHOS capacity will be expressed as oxygen flux normalised to muscle tissue wet weight (pmol O₂·s-¹·mg-¹ wet tissue).

  Baseline and after 6 weeks of supervised resistance training

• Change in Mitochondrial Oxidative Phosphorylation (OXPHOS) Capacity in Peripheral Blood Mononuclear Cells (PBMCs)

  Mitochondrial oxidative phosphorylation capacity will be assessed in permeabilised peripheral blood mononuclear cells (PBMCs) using high-resolution respirometry (Oxygraph-2k, Oroboros Instruments). OXPHOS capacity will be expressed as oxygen flux normalised to cell number (pmol O₂·s-¹·10⁶ cells-¹).

  Baseline and after 6 weeks of supervised resistance training

Secondary Outcomes (17)

• Change in Mitochondrial Quality Control Protein Expression in Skeletal Muscle

  Baseline and after 6 weeks of supervised resistance training

• Change in Whole-Body Lean Mass

  Baseline and after 6 weeks of supervised resistance training

• Change in Whole-Body Fat Mass

  Baseline and after 6 weeks of supervised resistance training

• Change in 6-Minute Walk Test Distance

  Baseline and after 6 weeks of supervised resistance training

• Change in Blood Glucose-6-Phosphate Dehydrogenase (G6PD) Activity

  Baseline and after 6 weeks of supervised resistance training

Study Arms (3)

Group of healthy trained old people

ACTIVE COMPARATOR

Elderly patient without diagnosis of type 2 diabetes mellitus

Other: Short-duration resistance training

Group of type 2 diabetic trained old patients

ACTIVE COMPARATOR

Elderly patient diagnosed with type 2 diabetes mellitus

Other: Short-duration resistance training

Group of healthy trained young people

ACTIVE COMPARATOR

Young healthy control subjects

Other: Short-duration resistance training

Interventions

Short-duration resistance training OTHER

The exercise program will be personalized (based on functional status). This program will consist of 12 sessions spread over 6 weeks, two days a week, and will increase in duration (30-50 minutes). The lower body muscle group, targeting the quadriceps, will be trained with two exercises: leg press and quadriceps extension. The training intensity will be submaximal, progressing toward maximum. All patient groups, both controls and cases, will receive the same type of training.

Group of healthy trained old people; Group of healthy trained young people; Group of type 2 diabetic trained old patients

Eligibility Criteria

• Age: 18 Years - 83 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy young adults (18-35 years old)
• Without any pathology or treatment
• Healthy older adults (65 years or older)
• Not currently enrolled in a resistance training program
• Age over 65 years
• Diagnosis of frailty or robustness
• Diagnosis of type 2 diabetes mellitus
• Glycosylated hemoglobin (HbA1c) less than 9%
• Treatment with metformin
• Not currently enrolled in a resistance training program

You may not qualify if:

• Pregnancy or suspected pregnancy
• Body mass index greater than 35 kg/m2
• Treatment within the last 30 days with oral corticosteroids
• Edema or severe fluid regulation disorders that could alter bioimpedance results
• Allergy to the local anesthetic mepivacaine
• Prostheses, metal implants, or surgical staples lodinated or barium contrast for other imaging tests within the last 7 days
• Decompensated and uncontrolled chronic diagnoses
• Body mass index greater than 35 kg/m2
• Treatment within the last 30 days with oral corticosteroids
• Systemic diseases, active oncological disease, liver cirrhosis, untreated hypothyroidism, or severe chronic obstructive pulmonary disease (COPD).
• Severe edema or fluid regulation disorders that could alter bioimpedance results
• Allergy to the local anesthetic mepivacaine
• Prostheses, metal implants, or surgical staples Iodinated or barium contrast for other imaging tests in the last 7 days
• Diagnosis of pre-frailty
• Age over 80 years

Sponsors & Collaborators

• Fundación para la Investigación del Hospital Clínico de Valencia: lead
• University of Valencia: collaborator
• Ministerio de Ciencia e Innovación, Spain: collaborator

Study Sites (1)

University of Valencia/Hospital Clínico Universitario de València,

Valencia, 46010, Spain

RECRUITING

Related Publications (14)

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MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Frailty

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Maria Carmen Gómez Cabrera, Doctor in Physiology

CONTACT

+34-666871805; carmen.gomez@uv.es

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2025
• First Posted: September 18, 2026
• Study Start: January 29, 2022
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): July 31, 2028
• Last Updated: September 18, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Time Frame: Beginning 12 months after publication of the primary results and for a period of 5 years thereafter.
• Access Criteria: Proposals should be directed to the principal investigator. Data will be shared via secure data transfer, following approval of a data-sharing agreement.

Locations

ES (1)