Molecular and Functional Basis of Successful Aging and Frailty
Overview
- Phase
- N/A
- Intervention
- Not specified
- Conditions
- Frailty Syndrome
- Sponsor
- Universita di Verona
- Enrollment
- 180
- Locations
- 1
- Primary Endpoint
- Structural cerebral cortex adaptations (TMS)
- Last Updated
- 5 years ago
Overview
Brief Summary
Frailty is the term commonly utilized to describe the geriatric syndrome that exposes the elderly to increased risk of negative health-related events. The frailty phenotypes (PF: physical or CF: cognitive) have demonstrated to predict the major negative health-related outcomes in the old population and show extensive similarities with sarcopenia (for PF) or dementia (for CF). However, the role of neurophysiological and biological factors contributing to the physical and cognitive frail condition, and in particular in which way mitochondrial dysfunction, as well as the hypertrophic and atrophic pathways assessed by genes expression, metabolomics and microbiota composition are contributing to these frail conditions, are still under debate. Therefore, the aim of this trial will be to make evidence based on the behaviors and the strategies that promote healthy lifestyle and successful human aging.
Detailed Description
In the majority of the world, the population is living to a greater age. However, older age is usually associated with elevated risk of several pathologies, as well as age-related organ dysfunctions, which in turn can accelerate functional impairments, disability, or death. To identify this geriatric syndrome the term frailty phenotype has been commonly utilized. In particular, the frailty phenotype can be distinguished in physical frailty (PF) phenotype or cognitive frailty (CF) phenotype. Despite several groups of researchers tried to develop preventive interventions to counteract the physical and cognitive frail condition of elderly, the success of this task has been tempered by the lack of standardized, and universally agreed protocols. Moreover, the limited knowledge of the neurophysiological, and biological determinants of these conditions has precluded important advances in the research of this domain. Many factors combine to achieve a successful aging: genetics, health care and healty lifestile. Therefore, the aim of the current trial will be to understand the behaviors and the strategies that promote healthy lifestyle and successful human aging. Oldest old participants with CF and PF will be selected from the neurorehabilitation unit of the University Hospital of Verona (Italy). Healthy oldest old and young participants will be recruited from the section of Movement Sciences of the University of Verona. After a first phase of neurophysiological and biological examinations that will involve all the 4 groups, only CF and PF participants will be randomly assigned to an intervention program (physical exercise, physical+cognitive exercise or control). Frail participants assigned to exercise groups will then perform 1 year of intervention, 3 days per week, 1 hour per day. Afterwards, the three groups of intervention will undergo the same neurophysiological and biological examinations of the beginning of the study.
Investigators
Massimo Venturelli, PhD
Research Fellow
Universita di Verona
Eligibility Criteria
Inclusion Criteria
- •YH: 30 healthy young (20-25 years old) participants. They must be free of any disease.
- •OH: 30 healthy oldest old (80-90 years old) participants. They must be free of any neural or physical disease and any severe chronic disease (CODP, Heart Failure) that can compromise exercise.
- •PF: 30 oldest old (80-90 years old) participants. They must be characterized by functional deficits (sarcopenia, osteoporosis and muscle weakness) without cognitive impairment. Additionally, participants cannot be affected by any severe chronic disease that compromise exercise.
- •CF: 30 oldest old (80-90 years old) participants. They must be characterized by mild cognitive impairment (MCI) and subjective cognitive decline without functional deficits. Additionally, participants cannot be affected by any severe chronic disease that compromise exercise.
- •Exclusion Criteria YH
- •Any medication
- •Any disease
- •General: pregnancy, addictive or previous addictive behavior defined as the abuse of cannabis, opioids or other drugs, carrier of infectious diseases.
- •For TMS: Epilepsy, metallic prosthesis, malignant tumor
- •Exclusion Criteria OH
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Structural cerebral cortex adaptations (TMS)
Time Frame: 3 years
Single-pulse TMS will be used to map the brain area representing the vastus lateralis (VL).
Expression of potential biomarkers (circulating miRNA)
Time Frame: 3 years
Noncoding RNAs, in particular, microRNAs (miRNAs), are a new regulatory system which plays a pivotal role in skeletal muscle adaptation and repairing.
Functional cerebral cortex adaptations (TMS)
Time Frame: 3 years
Single-pulse TMS will be used to investigate the excitability of the corticospinal system. A double-cone coil will be used to stimulate the leg area of the primary motor cortex (M1).
Modifications in the metabolism of cerebral areas (ASL-MRI)
Time Frame: 3 years
To assess non-invasively cerebral blood flow (CBF)
Muscle mass alterations (DXA)
Time Frame: 3 years
Muscle mass will be assessed with DXA
Alveolar profiles
Time Frame: 3 years
Changes in biogenic volatile organic compound concentrations can be used to mirror metabolic or pathophysiological processes in the whole body
Secondary Outcomes
- Changes in neuromuscular control 1(3 years)
- Changes in muscular fiber type(3 years)
- Changes in neuromuscular control 2(3 years)
- Mitochondrial Respiration(3 years)