Metabolic and Functional Consequences of Aging in Health and Disease

Study Overview
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Brief Summary
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Considerable heterogeneity in the aging population has been observed. The exceptional longevity of individuals reaching 100 years old, so-called centenarians may be an example of life-long healthy aging, or added years may be spent in poor health with decreased physical and cognitive functioning. Current knowledge of the aging experience and the trajectories of physical and cognitive decline across various age groups are not well-understood, yet crucial to prevent spending added years in disease. Hence, the study objective is to develop the metabolic profile associated with aging-related disorders measured as the incidence of impaired functional capacity, cognitive function, and/or well-being.

Detailed Description
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Our lab developed a pulse method combining multiple stable tracers to study multiple metabolic pathways in the same individual simultaneously. By measuring whole-body metabolism in a large group of older adults, we may be able to unravel age-related deterioration in protein turnover (synthesis and breakdown) that contributes to impaired functional capacity. Metabolic profiles could explain differences in pathways in the aging process with a special interest in the metabolism of amino acids as they have been associated with aging-related disorders. Studies on the effect of aging on metabolism might serve as potential therapeutic targets.

Official Title
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Metabolic and Functional Consequences of Aging in Health and Disease

Conditions
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Aging

Intervention / Treatment
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* Other: Stable tracer infusion in a postabsorptive state


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stable body-weight (± 5%) for the past 3 months Subject is judged to be in satisfactory health based on medical history, physical examination, and laboratory screening evaluations. Ability to walk, sit down and stand up independently or with walking mobility aids Ability to lie in a supine or elevated position for up to 3 hours Willingness and ability to comply with the protocol Exclusion Criteria: Insulin dependent diabetes mellitus Established diagnosis of malignancy History of untreated metabolic diseases including hepatic or renal disorder Presence of acute illness or metabolically unstable chronic illness Presence of fever within the last 3 days Use of short course of oral corticosteroids within 4 weeks preceding study day Failure to give informed consent or Investigator's uncertainty about the willingness or ability of the subject to comply with the protocol requirements (Possible) pregnancy Already enrolled in another clinical trial and that clinical trial interferes with participating in this study

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Controls<br>Study subjects that are eligible based on inclusion/exclusion criteria Screening visit: body weight and composition by DXA, height, and vital signs will be assessed. Study day(s): may include combinations of stable tracer infusions and with blood draws, cognitive and muscle performance testing | Other: Stable tracer infusion in a postabsorptive state<br>* Multiple stable-labeled tracers of amino acids, ketoacids, glycerol, short-chain fatty acids<br>* Other names: Stable tracer infusion;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Age-related changes in whole-body protein and amino acid metabolism | Whole-body production rate measured after stable tracer administration | 2 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Age-related changes in whole-body glucose metabolism | Whole-body production rate measured after stable tracer administration | 2 hours | 
| Age-related changes in whole-body fat metabolism | Whole-body production rate measured after stable tracer administration | 2 hours | 
| Age-related changes in depression as measured by the Hospital Anxiety and Depression Scale (HADS) and Geriatric Depression Scale (if applicable) | Self-reported depression measured by a validated questionnaire related to depression. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 (no symptoms) and 21 (severe symptoms). A higher score indicates a worse outcome (greater self-reported depression symptoms). | baseline visit | 
| Age-related changes in anxiety as measured by the Hospital Anxiety and Depression Scale (HADS) | Anxiety measured by a validated questionnaire related to anxiety-related symptoms. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 (no symptoms) and 21 (severe symptoms) related to anxiety. A higher score indicates a worse outcome (greater self-reported anxiety symptoms). | baseline visit | 
| Age-related changes in mood as measured by the Profile of Mood State (POMS) | A psychological distress scale to measure the mood disturbance in 6 domains - fatigue-inertia, vigor-activity, tension-anxiety, depression-dejection, anger-hostility, and confusion-bewilderment in the past week. Each item on the questionnaire is awarded a score from 0 (not at all) to 4 (extremely), except Relaxed and Efficient scored 4 (not at all) and 0 (extremely), based on the intensity of the assessed feeling in the past week. | baseline visit | 
| Age-related changes in health status | Health status assessed by Health-Related Quality of Life Scale (HR-QoL) | baseline visit | 
| Age-related changes in physical activity | Physical activity assessed by Physical Activity Scale for the Elderly (PASE) | baseline visit | 
| Age-related changes in sleep quality | Sleep quality assessed by Pittsburgh Sleep Quality Index | baseline visit | 
| Age-related changes in nutritional status | Nutritional status assessed by Mini-Nutritional Assessment | baseline visit | 
| Age-related changes in attention and executive functions as measured by Trail Making Test (TMT) | In Part A, the examinee is instructed to connect a set of 25 circles with numbers as quickly as possible while maintaining accuracy. In Part B, the examinee is instructed to connect a set of 25 circles, alternating between numbers and letters, as quickly as possible while maintaining accuracy. Measures attentional resources and is a measure of the frontal lobe executive functions of visual search, set-switching and mental flexibility. The total time in seconds was reported for each measure. | baseline visit | 
| Age-related changes in overall cognitive abilities as measured by Montreal Cognitive Assessment (MoCA) | MoCa assesses several cognitive domains and is used for the screening of mild cognitive impairment. Total scores range from 0-30 with lower scores indicating decreased functioning. | baseline visit | 
| Age-related changes in exercise capacity | Functional exercise capacity assessed by 6-minute walk test | baseline visit | 
| Age-related changes in physical weakness (frailty) | Physical weakness assessed by Short Physical Performance Battery | baseline visit | 
| Age-related changes in skeletal muscle strength of the upper extremity | Skeletal muscle strength measured by handgrip test | baseline visit | 
| Age-related changes in skeletal muscle strength of the lower extremity | Skeletal muscle strength measured by one-leg test | baseline visit | 
| Age-related changes in respiratory muscle strength | Respiratory muscle strength measured by a hand-held mouth pressure device (Micro RPM) | baseline visit | 
| Age-related changes in balance | Skeletal muscle strength measured by Berg Balance Scale and balance platform | baseline visit | 
| Age-related changes in gut microbiota | The amount and types of microbiota assessed in collected stool sample | baseline visit | 
| Age-related changes in gut function | Gut function assessed by Gastrointestinal Symptom Rating Scale, a 15-item instrument designed to assess the symptoms associated with common gastrointestinal disorders. A higher score indicates worse outcomes (more discomfort). | baseline visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stable isotopes, disease, metabolism