Targeting Aging and Promoting Longevity With Exogenous Nucleotides (TALENTs)

Study Overview
=================
Brief Summary
-----------------
To investigate the effects of dietary nucleotides (NTs) as an anti-aging supplement, a clinical trial is carried as a randomized, double-blind, parallel design, placebo-controlled. A total of 120 subjects will be enrolled in the study, and they shall be randomly distributed between the two arms, NTs-treated, and placebo-control. They would be given several measurements, including physical examination, questionnaire survey, clinical and aging-related biomarkers tests at 0 (baseline), 2, and 4 months during the RCT.

Detailed Description
-----------------
To explore the anti-aging effects of NTs and the regulation of aging-related diseases, this study plans to recruit 120 people as subjects and conduct randomized controlled trials with NTs as an intervention for 4 months. Based on computer-generated random numbers, participants who meet the inclusion criteria are randomly assigned equally to two groups: placebo control and nucleotide intervention groups. In this study, the specific nucleotide composition is 5'-AMP、5'-CMP、5'-GMPNa2、5'-UMPNa2 prepared according to the ratio of 16:41:19:24, which is consistent with the ratio in breast milk and meets the requirements of national infant formula addition and special medical food formula. The dose of 1.2 g/day used is currently approved as the ingredient dose of nucleotides in conventional commercially available health food products. At the 0、2 and 4 months of the study, comprehensive geriatric health assessment, aging biomarker testing and biological sample collection will be conducted. Among them, the comprehensive evaluation of elderly health status is carried out by physical examination and questionnaire survey, including physical health, physiological function, quality of life, cognitive function, psychosocial health, and other aspects of information. The physical examination involves both physical assessment and functional assessment, including body composition, neck circumference, waist circumference, hip circumference, middle arm circumference, calf circumference, BMR, grip strength, six-minute walk, intima-media thickness, subcutaneous AGEs, and spirometry. The scale includes health status, nutritional status, cognitive status, physical activity, and dietary status. Blood samples were used to detect the safety and senescence-related indicators of the subjects. The index system covers four modules and seventeen dimensions, including blood routine, blood biochemistry, inflammatory factors, immune antibodies, T lymphocyte subtypes, oxidative stress level, cancer markers, leukocyte telomere length, DNA methylation, γ-H2A. Blood samples are sequenced simultaneously for gene and transcriptome sequencing. Fecal samples are collected for metagenomic sequencing of intestinal flora.

Official Title
-----------------
A Randomized Controlled Trial Study To Evaluated the Effect of Exogenous Nucleotides as an Anti-ageing Supplement in Older Adults (60-70 Years)

Conditions
-----------------
Aging

Intervention / Treatment
-----------------
* Dietary Supplement: dietary nucleotides
* Dietary Supplement: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male/females of 60 to 70 years of age No serious physical or mental illness Able to provide written Informed Consent Able to follow verbal and written study directions Must not be taking or be willing to take any supplements containing any form of nucleotides for one year prior to baseline and for the duration of the study. Able to maintain consistent diet and lifestyle habits throughout the study Willing to consume assigned supplement (NTs or placebo) for 4 months Exclusion Criteria: Participants on the current use of prescription or over-the-counter nucleotides Having abnormal screening laboratory test values or other lab test result(s) that would preclude study participation in the judgment of the investigator Documented presence of atherosclerotic disease and/or cardiopulmonary disease History of drug or alcohol abuse History of unstable depression or mental illness within the last 6 months for which the investigator believes could impact the participant's ability to comply with study requirements Other diseases or medications, according to the investigator, that would interfere directly in the results of the study or jeopardize the health of the participant. Currently, or within the past 30 days, enrolled in a different clinical investigation Inability to provide a venous blood sample Unable or unwilling to provide written informed consent for participation in the study

Ages Eligible for Study
-----------------
Minimum Age: 60 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: completely randomized design
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NTs Intervention group<br>The subject of 1200mg has been given orally once a day for 4 months. | Dietary Supplement: dietary nucleotides<br>* 1.2 g/d NTs (5 '-AMP, 5' -CMP, 5 '-GMPNa2, 5' -UMPNa2) ;<br>|
| Placebo Comparator: placebo control group<br>The ingredients, dosage, and usage are the same as experimental. | Dietary Supplement: placebo<br>* placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phenotypic Age | Phenotypic Age=141:50+ln(0.00553*ln(1-xb)). xb=-19:907-0.0336*albuminþ+0.095*creatinine+0.0195*glucose+0.0954*lnCRP-0.0120*lymphocyte percent+0.0268 mean cell volume+0.3356 red blood cell distribution width+0.00188 alkaline phosphatase+0.0554*white blood cell count+0.0804*chronological age | Baseline | 
| Phenotypic Age | Phenotypic Age=141:50+ln(0.00553*ln(1-xb)). xb=-19:907-0.0336*albuminþ+0.095*creatinine+0.0195*glucose+0.0954*lnCRP-0.0120*lymphocyte percent+0.0268 mean cell volume+0.3356 red blood cell distribution width+0.00188 alkaline phosphatase+0.0554*white blood cell count+0.0804*chronological age | At 2 months | 
| Phenotypic Age | Phenotypic Age=141:50+ln(0.00553*ln(1-xb)). xb=-19:907-0.0336*albuminþ+0.095*creatinine+0.0195*glucose+0.0954*lnCRP-0.0120*lymphocyte percent+0.0268 mean cell volume+0.3356 red blood cell distribution width+0.00188 alkaline phosphatase+0.0554*white blood cell count+0.0804*chronological age | At 4 months | 
| The levels of SOD | In serum | Baseline | 
| The levels of SOD | In serum | At 2 months | 
| The levels of SOD | In serum | At 4 months | 
| The levels of GSH-Px | In serum | Baseline | 
| The levels of GSH-Px | In serum | At 2 months | 
| The levels of GSH-Px | In serum | At 4 months | 
| The levels of MDA | In serum | Baseline | 
| The levels of MDA | In serum | At 2 months | 
| The levels of MDA | In serum | At 4 months | 
| Carotid thickness of intima media | ultrasound | Baseline | 
| Carotid thickness of intima media | ultrasound | At 2 months | 
| Carotid thickness of intima media | ultrasound | At 4 months | 
| Spontaneous fluorescence of subcutaneous AGEs | AGEs test | Baseline | 
| Spontaneous fluorescence of subcutaneous AGEs | AGEs test | At 2 months | 
| Spontaneous fluorescence of subcutaneous AGEs | AGEs test | At 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body composition | BIA method - fat mass (grams), lean mass (grams) and total mass (grams). | Baseline | 
| Body composition | BIA method - fat mass (grams), lean mass (grams) and total mass (grams). | At 2 months | 
| Body composition | BIA method - fat mass (grams), lean mass (grams) and total mass (grams). | At 4 months | 
| Body circumference | Measured with a soft tape - waist, hip, mid-arm, neck and calf circumference | Baseline | 
| Body circumference | Measured with a soft tape - waist, hip, mid-arm, neck and calf circumference | At 2 months | 
| Body circumference | Measured with a soft tape - waist, hip, mid-arm, neck and calf circumference | At 4 months | 
| Gait speed | 6m walking time/speed test | Baseline | 
| Gait speed | 6m walking time/speed test. | At 2 months | 
| Gait speed | 6m walking time/speed test. | At 4 months | 
| The score of the Short Physical Performance Battery (SPPB) | The SPPB is a composite test that includes assessments of gait speed, a balance test, and a chair stand test. The maximum score is 12 points, and a score of ≤ 8 points indicates poor physical performance. | Baseline | 
| The score of the Short Physical Performance Battery (SPPB) | The SPPB is a composite test that includes assessments of gait speed, a balance test, and a chair stand test. The maximum score is 12 points, and a score of ≤ 8 points indicates poor physical performance. | At 2 months | 
| The score of the Short Physical Performance Battery (SPPB) | The SPPB is a composite test that includes assessments of gait speed, a balance test, and a chair stand test. The maximum score is 12 points, and a score of ≤ 8 points indicates poor physical performance. | At 4 months | 
| Time costs of TUG | For the Timed-Up and Go test, individuals are asked to rise from a standard chair, walk to a marker 3 m away, turn around, walk back and sit down again. | Baseline | 
| Time costs of TUG | For the Timed-Up and Go test, individuals are asked to rise from a standard chair, walk to a marker 3 m away, turn around, walk back and sit down again. | At 2 months | 
| Time costs of TUG | For the Timed-Up and Go test, individuals are asked to rise from a standard chair, walk to a marker 3 m away, turn around, walk back and sit down again. | At 4 months | 
| Grip strength | Calibrated handheld dynamometer. | Baseline | 
| Grip strength | Calibrated handheld dynamometer. | At 2 months | 
| Grip strength | Calibrated handheld dynamometer. | At 4 months | 
| Weekly physical activity Energy expenditure | Activities of daily living (ADL). Weekly physical activity Energy expenditure = Physical activity intensity (MET) * time spent per day * days spent per week (MET= METn HN/h), According to the International Physical Activity Scale (IPAQ), the elderly were divided into three levels of physical activity: low (less than 600 METs/ week), medium (600 3 000 METs/ week) and high (over 3 000 METs/ week) | Baseline | 
| Weekly physical activity Energy expenditure | Activities of daily living (ADL). Weekly physical activity Energy expenditure = Physical activity intensity (MET) * time spent per day * days spent per week (MET= METn HN/h), According to the International Physical Activity Scale (IPAQ), the elderly were divided into three levels of physical activity: low (less than 600 METs/ week), medium (600 3 000 METs/ week) and high (over 3 000 METs/ week) | At 4 months | 
| Pittsburgh sleep quality index (PSQI) | Items are categorized into seven components: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, sleep medication, and daytime dysfunction. The possible score range for each component is 0 (no difficulty) to 3 (severe difficulty). The seven component scores are summed to produce a global score; higher scores represent poorer subjective sleep quality. | Baseline | 
| Pittsburgh sleep quality index (PSQI) | Items are categorized into seven components: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, sleep medication, and daytime dysfunction. The possible score range for each component is 0 (no difficulty) to 3 (severe difficulty). The seven component scores are summed to produce a global score; higher scores represent poorer subjective sleep quality. | At 4 months | 
| Score of Montreal Cognitive Assessment (MoCA) | Scores range from 0-30 (+1 for 12 or fewer years of education); a score of 26 or higher indicates normal cognitive functioning, while a score of 25 or lower indicates impaired functioning. | Baseline | 
| Score of Montreal Cognitive Assessment (MoCA) | Scores range from 0-30 (+1 for 12 or fewer years of education); a score of 26 or higher indicates normal cognitive functioning, while a score of 25 or lower indicates impaired functioning. | At 4 months | 
| The levels of TNF-α in serum | Suspension array | Baseline | 
| The levels of TNF-α in serum | Suspension array | At 4 months | 
| The levels of IL-1 in serum | Suspension array | Baseline | 
| The levels of IL-1 in serum | Suspension array | At 4 months | 
| The levels of IL-6 in serum | Suspension array | Baseline | 
| The levels of IL-6 in serum | Suspension array | At 4 months | 
| The levels of MCP-1 in serum | Suspension array | Baseline | 
| The levels of MCP-1 in serum | Suspension array | At 4 months | 
| The levels of ICAM-1 in serum | Suspension array | Baseline | 
| The levels of ICAM-1 in serum | Suspension array | At 4 months | 
| Methylation damage | Blood sample | Baseline | 
| Methylation damage | Blood sample | At 4 months | 
| The level of telomere repeat binding factors-1 (TRF-1) | Blood sample | Baseline | 
| The level of telomere repeat binding factors-1 (TRF-1) | Blood sample | At 4 months | 
| The level of telomere repeat binding factors-2 (TRF-2) | Blood sample | Baseline | 
| The level of telomere repeat binding factors-2 (TRF-2) | Blood sample | At 4 months | 
| The length of Leukocyte telomere | Blood sample | Baseline | 
| The length of Leukocyte telomere | Blood sample | At 4 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
telomerase, anti-aging