Metabolic Control of Aging and Disease - the MetAGE Deep Phenotyping Cohort (Pro-Metage)

Metabolic Control of Aging and Disease - the MetAGE Deep Phenotyping Cohort (Pro-Metage)

The goal of this prospective observational study is to identify and validate blood based aging biomarkers in relation to cardiometabolic phenotypes of young and old, female and male subjects with or without obesity.

The main question is to gain insights into the interaction of obesity related metabolic alteration and aging, and the relevance of loss of metabolic control in the development of age-related diseases in order to build a foundation for targeted drug- and lifestyle interventions in future studies.

Study Overview

• Status: Recruiting
• Conditions: Obesity; Metabolic Syndrome; Aging; Aging Problems
• Intervention / Treatment: Diagnostic test: comprehensive metabolic phenotyping

Detailed Description

The ongoing increase in human life expectancy is steadily reshaping the demographic landscape, leading to a higher proportion of older adults, many of whom suffer from multiple health conditions. These unprecedented demographic shifts come at a significant socioeconomic cost, as aging stands as the primary risk factor for chronic disabilities and disorders such as cardiovascular diseases, dementia, type 2 diabetes, obesity, steatotic liver disease and infections. Consequently, promoting healthy aging emerges as one of the most pressing societal challenges in the foreseeable future, underscoring the urgent need for clinically validated strategies to extend the disease-free phase of life, known as health span.

The Pro-MetAGE prospective cohort as part of the clinical program of the MetAGE Cluster of Excellence (Austrian Science Fund # 10.55776/COE14) will focus on understanding the metabolic dysregulation associated with aging in a metabolic at-risk population. Metabolic control, which encompasses various aspects and is influenced by numerous aging indicators, might be the primary driver of age-related diseases. For instance, contemporary markers of biological age, such as epigenetic clocks based on DNA methylation and cellular senescence markers, correlate more closely with metabolic processes like nutrient sensing and mitochondrial function rather than genome stability or telomere length.

Aging entails a gradual deterioration of several fundamental metabolic processes, including lipostasis (fat metabolism), proteostasis (protein homeostasis), polyamine metabolism, and mitochondrial function. These intracellular changes are compounded by alterations in intercellular and interorgan communication, affecting brain-organ interactions and immune function. The decline in these crucial processes can disrupt the regulatory mechanisms of metabolic control in a manner influenced by sex and gender. Consequently, the loss of metabolic control may exacerbate other aging processes, setting off a detrimental cycle of accelerated aging.

Disruption in metabolic regulation caused by calorie-rich diets, disturbed circadian rhythms, or sedentary lifestyle can lead to a diverse set of health issues known collectively as metabolic syndrome. These medical conditions, including obesity, high blood pressure, elevated lipid levels, insulin resistance, and high blood sugar, contribute to the development of prevalent age-related diseases such as cardiovascular disease, type 2 diabetes, retinal degeneration and metabolic dysfunction-associated steatotic liver disease, formerly known as nonalcoholic fatty liver disease, affecting millions of older individuals globally. Additionally, there exists a significant link between metabolic imbalance and dysfunction in the immune system, resulting in heightened susceptibility to infections, diminished response to vaccinations, and various neuropsychiatric disorders, especially depression. Hence, understanding the mechanisms underlying metabolic dysregulation holds immense importance in devising preventive measures against some of the most debilitating age-related ailments.

The proposed research project aims to prospectively identify and validate aging biomarkers in relation to age- and sex-related cardiometabolic changes in young and old individuals, who are lean or obese/overweight (i.e. a metabolic at-risk population) with regard to lipostasis, proteostasis, polyamine metabolism, mitochondrial function, inflammation and cellular senescence. The goal is to gain insights into the interaction of obesity related metabolic alteration and aging, and the relevance of loss of metabolic control in the development of age-related diseases in order to build a foundation for targeted drug- and lifestyle interventions in future studies.

• Study Type: Observational
• Enrollment (Estimated): 650

Contacts and Locations

Study Locations

• Austria
  • Styria
    • Graz, Styria, Austria
      • Recruiting
      • Medical University of Graz
      • Contact: Thomas Pieber, MD, Prof.; Phone Number: +43 316 385 82383; Email: thomas.pieber@medunigraz.at
  • Vienna
    • Vienna, Vienna, Austria
      • Recruiting
      • Medical University of Vienna
      • Contact: Thomas Scherer, MD; Phone Number: +43 1 40400 43121; Email: thomas.scherer@meduniwien.ac.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Community sample from eastern Austria.

Description

Inclusion Criteria:

Group 1 - Lean, young adults (n = 150)

• Age 18 - 35 years
• Body mass index (BMI) ≥ 18.5 and ≤ 24.9 kg/m2 (≥ 12 months)

Group 2 - Overweight, young adults (n = 150)

• Age 18 - 35 years
• BMI ≥ 28kg/m2 (≥ 12 months)

Group 3 - Lean, older adults (n = 150)

• Age ≥ 60 years
• BMI ≥ 18.5 and ≤ 24.9 kg/m2 (≥ 3 years)

Group 4 - Overweight, older adults (n = 150)

• Age ≥ 60 years
• BMI ≥ 28 kg/m2 (≥ 3 years)
• Subgroup A (n=75): with pre-existent cardiovascular disease defined as: history of myocardial infarction or evidence of coronary artery disease irrespective of revascularization status or history of ischemic or hemorrhagic stroke or presence of peripheral artery disease or heart failure with preserved ejection fraction (NYHA Class I-II).
• Subgroup B (n=75): without pre-existent cardiovascular disease

Group 5 - Nonagenerians Age ≥ 90 (n = 50)

• Age ≥ 90 years
• BMI ≥ 18.5 kg/m2 (≥ 3 years)

Exclusion Criteria:

Group 1 - Lean, young adults (n = 150)

• Highly physical active (i.e. > 5 times sporting activity / week with moderate to high intensity [heart rate 140 - 200bpm])
• Special diets (i.e. ketogenic diet and time-restricted eating)
• Clinically significant metabolic or endocrine disorders
• Claustrophobia
• drug abuse, alcohol > 15 drinks/week
• Heart failure, cardiovascular disease, immunosuppressive therapies, chronic inflammatory diseases and active oncologic conditions
• Metal implants that prohibit 3T MRI
• Pregnancy or breastfeeding

Group 2 - Overweight, young adults (n = 150)

• Highly physical active (i.e. > 5 times sporting activity / week with moderate to high intensity [heart rate 140 - 200bpm])
• Special diets (i.e. ketogenic diet and time-restricted eating)
• Active anti-obesity treatment (e.g. glucagon-like peptide 1 (GLP-1) analogues, polyagonists, naltrexone and bupropion)
• Clinically significant metabolic or endocrine disorders
• Claustrophobia
• drug abuse, alcohol > 15 drinks/week
• Heart failure, cardiovascular disease, immunosuppressive therapies, chronic inflammatory diseases and active oncologic conditions
• Metal implants that prohibit 3T MRI
• Pregnancy or breastfeeding

Group 3 - Lean, older adults (n = 150)

• Highly physical active (i.e. > 5 times sporting activity / week with moderate to high intensity [heart rate 140 - 200bpm])
• Special diets (i.e. ketogenic diet and time-restricted eating)
• Diabetes, overt hypo/hyperthyroidism
• Claustrophobia
• drug abuse, alcohol > 15 drinks/week
• Metal implants that prohibit 3T MRI
• Known severe cardiovascular diseases (i.e. PAD IIa or higher, advanced heart failure = left ventricular ejection fraction (LVEF) < 35% or NYHA Class III-IV)
• No previous heart failure, cardiovascular disease, immunosuppressive therapies, chronic inflammatory diseases and active oncologic conditions up until the age of 35 years.
• Life-threatening conditions with a life expectancy of less than 1 year or any other condition that would jeopardize proband safety/adherence while participating in this trial.

Group 4 - Overweight, older adults (n = 150)

• Special diets (i.e. ketogenic diet and time-restricted eating)
• Diabetes, overt hypo/hyperthyroidism
• Active anti-obesity treatment (e.g. GLP-1 analogues, polyagonists, naltrexone and bupropion)
• Claustrophobia
• drug abuse, alcohol > 15 drinks/week
• Metal implants that prohibit 3T MRI
• No previous heart failure, cardiovascular disease, immunosuppressive therapies, chronic inflammatory diseases and active oncologic conditions up until the age of 35 years.
• Life-threatening conditions with a life expectancy of less than 1 year or any other condition that would jeopardize proband safety/adherence while participating in this trial.

Group 5 - "healthy" Nonagenerians Age ≥ 90 (n = 50)

• Claustrophobia
• Clinically significant cognitive impairment compromising study adherence
• Metal implants that prohibit 3T MRI
• Life-threatening conditions with a life expectancy of less than 1 year or any other condition that would jeopardize proband safety/adherence while participating in this trial.

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Lean, young adults	Diagnostic test: comprehensive metabolic phenotyping; The investigators will employ state of the art techniques to metabolically phenotype the study groups using brain, cardiac and whole body magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), wearables, optical coherence tomography longitudinally. In addition, a battery of patient reported outcome measures will be used to explore psychosocial aspects of aging.
Overweight, young adults	Diagnostic test: comprehensive metabolic phenotyping; The investigators will employ state of the art techniques to metabolically phenotype the study groups using brain, cardiac and whole body magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), wearables, optical coherence tomography longitudinally. In addition, a battery of patient reported outcome measures will be used to explore psychosocial aspects of aging.
Lean, older adults	Diagnostic test: comprehensive metabolic phenotyping; The investigators will employ state of the art techniques to metabolically phenotype the study groups using brain, cardiac and whole body magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), wearables, optical coherence tomography longitudinally. In addition, a battery of patient reported outcome measures will be used to explore psychosocial aspects of aging.
Overweight, older adults	Diagnostic test: comprehensive metabolic phenotyping; The investigators will employ state of the art techniques to metabolically phenotype the study groups using brain, cardiac and whole body magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), wearables, optical coherence tomography longitudinally. In addition, a battery of patient reported outcome measures will be used to explore psychosocial aspects of aging.
Nonagenerians Age ≥ 90; Note: Nonagenarian Group will only be phenotyped once	Diagnostic test: comprehensive metabolic phenotyping; The investigators will employ state of the art techniques to metabolically phenotype the study groups using brain, cardiac and whole body magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), wearables, optical coherence tomography longitudinally. In addition, a battery of patient reported outcome measures will be used to explore psychosocial aspects of aging.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biological age: Epigenetic and clinical clocks	Epigenetic and clinical clocks (i.e. LinAge2, PheoAge) will be measured assessing DNA methylation in whole blood and standard laboratory parameters. The investigators speculate that the biological age is accelerated in obesity/overweight persons independent of chronological age.	every 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Magnetic resonance spectroscopy	Hepatic lipid content	every 3 years
Magnetic resonance imaging	Whole body fat distribution	every 3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vibration-controlled transient elastography	Liver stiffness, Hepatic lipid content	every 3 years
Body composition	Air Displacement Plethysmograph with BodPod	every 3 years
Continuous glucose monitoring	Continuous blood glucose monitoring over 2 weeks will be performed	every 3 years
Retina scans	Optical coherence tomography angiography	every 3 years
Physical activity	Wrist-based actigraphy will be used to assess physical activity	every 3 years

Collaborators and Investigators

• Sponsor: Thomas Scherer
• Collaborators: Medical University of Graz; University of Graz

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2025
• Primary Completion (Estimated): January 1, 2035
• Study Completion (Estimated): January 1, 2036

Study Registration Dates

• First Submitted: July 9, 2024
• First Submitted That Met QC Criteria: July 15, 2024
• First Posted (Actual): July 19, 2024

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 13, 2026
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Insulin Resistance; Hyperinsulinism; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Metabolic Syndrome
• Other Study ID Numbers: 1632/2024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No