Back to results

Role of MicroRNAs on Age and Contraction-induced Skeletal Muscle Growth

Primary Purpose

Sarcopenia

Status

Unknown status

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Acute Resistance Exercise

About this trial

This is an interventional basic science trial for Sarcopenia focused on measuring Exercise, Anabolic Resistance, Skeletal Muscle, microRNA

Eligibility Criteria

20 Years - 85 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Male and Female
20-30 or 70-85 years of age
Sedentary: Must not participate in any regular exercise sessions (participants who walk regularly or walk for exercise are eligible)
Individuals must confirm good health
BMI must be between 19-35 kg/m2
Individuals must be fluent in English
Willing to come to the HNRCA laboratory for study visits
Short Physical Performance Battery of less than 9 (70-85 years of age cohort)
10 subjects with Normal Muscle Mass and 10 subjects with Low Muscle Mass as determined by DXA scan (70-85 years of age cohort) Low Muscle Mass is defined as Class I Sarcopenia, Skeletal Muscle Index within 1 to 2 standard deviations from the sex-specific mean of young adults

Exclusion Criteria:

Lost or gained 7.5% or more of their body weight in the past 6 months
Acute or terminal disease
Significant immune disorder
Types I and II Diabetes mellitus
Uncontrolled hypertension (>180/100 mmHg)
Neuromuscular disease
Subjects must also not be participating in any regular endurance or resistance training exercise during the previous six months.
Mini-mental state examination (MMSE) score of <23
Because of the DXA scan and the unknown risk associated with the muscle biopsy procedure, women who are pregnant, planning to become pregnant, or are breastfeeding will be excluded from the study.

Subjects with a history of any of the following within the past 6 months will be excluded:

Myocardial infarction in the past 6 months, or other symptomatic coronary artery disease.
Surgery in previous 6 months
Upper or lower extremity fracture in the previous 6 months
Allergy to lidocaine

Subjects currently taking any of the following drugs or classes of drugs will be excluded:

Anticoagulant therapy (Warfarin, Coumadin, or Plavix)
ACE inhibitors
Drugs that affects neuromuscular function
Angiotensin receptor blockers
Androgen or estrogen therapy or other hormone replacement therapy
Low dose aspirin with known cardiovascular disease (e.g.: reported coronary artery disease, peripheral vascular disease, or previous stroke, or history of transient ischemic attacks)
Diabetes medications (ie. metformin, insulin therapy, thiazolidinediones, sulfonylureas etc.)
Chronic corticosteroid therapy

Laboratory blood test exclusions:

Estimated GFR <30 mL/min/1.73m2
Other abnormal screening lab values will be at the discretion of the study physician

Sites / Locations

Human Nutrition Research Center on Aging at Tufts University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Arm Label

HL-YNG

FL-OLD

SR-OLD

Arm Description

Healthy young sedentary males and females 20-30 yrs old Participants will undergo an acute bout of resistance exercise at 80% of their 1 repetition maximum (1RM, maximum strength) and will undergo muscle biopsies before, immediately after and 4 hours after the exercise.

Functionally-limited older sedentary males and females without sarcopenia (70-85 yrs old) Participants will undergo an acute bout of resistance exercise at 80% of their 1 repetition maximum (1RM, maximum strength) and will undergo muscle biopsies before, immediately after and 4 hours after the exercise.

Functionally-limited older sedentary males and females with clinically defined sarcopenia (70-85 yrs old) Participants will undergo an acute bout of resistance exercise at 80% of their 1 repetition maximum (1RM, maximum strength) and will undergo muscle biopsies before, immediately after and 4 hours after the exercise.

Outcomes

Primary Outcome Measures

Change of microRNA expression in humans skeletal muscle after an acute bout of high intensity resistance exercise

Determine if the expression of miRNA in skeletal muscle after an acute bout of high-intensity resistance exercise in young, functionally-limited older adults with and without low muscle mass

Secondary Outcome Measures

Full Information

NCT ID

NCT02638454

First Posted

December 17, 2015

Last Updated

July 16, 2021

Sponsor

Tufts University

1. Study Identification

Unique Protocol Identification Number

NCT02638454

Brief Title

Role of MicroRNAs on Age and Contraction-induced Skeletal Muscle Growth

Official Title

Role of MicroRNAs on Age and Contraction-induced Skeletal Muscle Growth

Study Type

Interventional

2. Study Status

Record Verification Date

July 2021

Overall Recruitment Status

Unknown status

Study Start Date

August 2015 (undefined)

Primary Completion Date

January 2022 (Anticipated)

Study Completion Date

January 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Tufts University

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Sarcopenia is a predictor of functional-limitation, leading to loss of independence, lowered quality of life, and ultimately death. The impaired ability of aged skeletal muscle to adapt to anabolic stimulation may be a factor that contributes to sarcopenia. This project will provide novel insights into the role of microRNA in the attenuation of aging skeletal muscle to changes in gene expression after anabolic stimulation.

Detailed Description

The age-associated loss of skeletal muscle mass and function (sarcopenia) is associated with substantial social and economic costs. The plasticity and adaptability of skeletal muscle to contraction (ie. resistance-exercise) is a fundamental physiological event leading to larger and more robust skeletal muscle. However, muscle growth in response to resistance exercise (RE), like other anabolic stimuli, is attenuated in older adults. The cause of aberrant muscle adaptation with aging is complex. Recent work has revealed a novel role for small non-coding RNAs, called microRNAs (miRNA) in the regulation of gene expression. Using an integrated bioinformatics analysis of protein-coding gene and miRNA array data from young and older men, I identified ten specific miRNAs as important regulators of muscle plasticity (Plasticity Related miRs [PR-miRs]) leading to the transcriptional response to exercise and lean mass in young and older men. However, the precise mechanisms underlying the expression of PR-miRs on age-related changes in muscle anabolism and sarcopenia are currently unknown. Thus, the overall objective of this K01 application will be to determine the mechanistic role(s) of these PR-miRs in skeletal muscle adaptation to anabolic stimulation in: healthy young, sarcopenic older and age- and functionally-matched non-sarcopenic older males and females. This will be accomplished by determine the differences in expression of PR-miRs with aging and sarcopenia in response to anabolic stimulation (AIM 1). Mechanistically determine the extent to which manipulation of PR-miR levels in vitro, in human primary myocytes, can reverse anabolic resistance observed with age and sarcopenia (AIM 2) and the effect of altering PR-miRs levels on skeletal muscle growth and development (AIM 3). This project will improve our understanding of the molecular mechanisms that contribute to the loss of skeletal muscle and eventually leading to the development of drug therapies for the treatment of sarcopenia in the ever growing aging population.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Sarcopenia

Keywords

Exercise, Anabolic Resistance, Skeletal Muscle, microRNA

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

Investigator

Allocation

Non-Randomized

Enrollment

30 (Actual)

8. Arms, Groups, and Interventions

Arm Title

HL-YNG

Arm Type

Active Comparator

Arm Description

Arm Title

FL-OLD

Arm Type

Experimental

Arm Description

Arm Title

SR-OLD

Arm Type

Experimental

Arm Description

Intervention Type

Procedure

Intervention Name(s)

Acute Resistance Exercise

Other Intervention Name(s)

Acute Strength Training

Intervention Description

1 bout of high-intensity resistance exercise at 80% of the individuals 1 repetition maximum

Primary Outcome Measure Information:

Title

Change of microRNA expression in humans skeletal muscle after an acute bout of high intensity resistance exercise

Description

Determine if the expression of miRNA in skeletal muscle after an acute bout of high-intensity resistance exercise in young, functionally-limited older adults with and without low muscle mass

Time Frame

Baseline, immediately (within 15-30 min after acute resistance exercise) and 4 hours after acute resistance exercise

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male and Female 20-30 or 70-85 years of age Sedentary: Must not participate in any regular exercise sessions (participants who walk regularly or walk for exercise are eligible) Individuals must confirm good health BMI must be between 19-35 kg/m2 Individuals must be fluent in English Willing to come to the HNRCA laboratory for study visits Short Physical Performance Battery of less than 9 (70-85 years of age cohort) 10 subjects with Normal Muscle Mass and 10 subjects with Low Muscle Mass as determined by DXA scan (70-85 years of age cohort) Low Muscle Mass is defined as Class I Sarcopenia, Skeletal Muscle Index within 1 to 2 standard deviations from the sex-specific mean of young adults Exclusion Criteria: Lost or gained 7.5% or more of their body weight in the past 6 months Acute or terminal disease Significant immune disorder Types I and II Diabetes mellitus Uncontrolled hypertension (>180/100 mmHg) Neuromuscular disease Subjects must also not be participating in any regular endurance or resistance training exercise during the previous six months. Mini-mental state examination (MMSE) score of <23 Because of the DXA scan and the unknown risk associated with the muscle biopsy procedure, women who are pregnant, planning to become pregnant, or are breastfeeding will be excluded from the study. Subjects with a history of any of the following within the past 6 months will be excluded: Myocardial infarction in the past 6 months, or other symptomatic coronary artery disease. Surgery in previous 6 months Upper or lower extremity fracture in the previous 6 months Allergy to lidocaine Subjects currently taking any of the following drugs or classes of drugs will be excluded: Anticoagulant therapy (Warfarin, Coumadin, or Plavix) ACE inhibitors Drugs that affects neuromuscular function Angiotensin receptor blockers Androgen or estrogen therapy or other hormone replacement therapy Low dose aspirin with known cardiovascular disease (e.g.: reported coronary artery disease, peripheral vascular disease, or previous stroke, or history of transient ischemic attacks) Diabetes medications (ie. metformin, insulin therapy, thiazolidinediones, sulfonylureas etc.) Chronic corticosteroid therapy Laboratory blood test exclusions: Estimated GFR <30 mL/min/1.73m2 Other abnormal screening lab values will be at the discretion of the study physician

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Donato A Rivas, PhD

Organizational Affiliation

Tufts University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Human Nutrition Research Center on Aging at Tufts University

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02111

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Learn more about this trial

Role of MicroRNAs on Age and Contraction-induced Skeletal Muscle Growth

We'll reach out to this number within 24 hrs