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Targeting Aging and Promoting Longevity with Exogenous Nucleotides (TALENTs)

Not Applicable
Completed
Conditions
Aging
Interventions
Dietary Supplement: placebo
Dietary Supplement: dietary nucleotides
Registration Number
NCT05243108
Lead Sponsor
Peking University
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
122
Inclusion Criteria
  1. Male/females of 60 to 70 years of age
  2. No serious physical or mental illness
  3. Able to provide written Informed Consent
  4. Able to follow verbal and written study directions
  5. 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.
  6. Able to maintain consistent diet and lifestyle habits throughout the study
  7. Willing to consume assigned supplement (NTs or placebo) for 4 months
Exclusion Criteria
  1. Participants on the current use of prescription or over-the-counter nucleotides
  2. Having abnormal screening laboratory test values or other lab test result(s) that would preclude study participation in the judgment of the investigator
  3. Documented presence of atherosclerotic disease and/or cardiopulmonary disease
  4. History of drug or alcohol abuse
  5. 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
  6. 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.
  7. Currently, or within the past 30 days, enrolled in a different clinical investigation
  8. Inability to provide a venous blood sample
  9. Unable or unwilling to provide written informed consent for participation in the study

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
placebo control groupplaceboThe ingredients, dosage, and usage are the same as experimental.
NTs Intervention groupdietary nucleotidesThe subject of 1200mg has been given orally once a day for 4 months.
Primary Outcome Measures
NameTimeMethod
DNAmAgeBaseline、At 2 months、At 4 months

DNA methylation clocks were assessed through whole-genome bisulfite sequencing (WGBS).The median of four principal component (PC)-corrected clocks (Horvath, Hannum, GrimAge, and PhenoAge) was chosen as the DNA methylation age outcome measure.

The length of Leukocyte telomereBaseline、At 2 months、At 4 months

Telomere length was quantified via quantitative PCR, using telomeric DNA amplification compared to a reference gene.

Secondary Outcome Measures
NameTimeMethod
γH2AXBaseline、 At 2 months、 At 4 months

Phosphorylated histone H2AX (p-H2AX) was measured via ELISA

glycolipid metabolic profileBaseline、 At 2 months、 At 4 months

fasting glucose, glycated hemoglobin, fasting insulin, HOMA-IR, triglycerides, total cholesterol, LDL-C, HDL-C

Body compositionBaseline、At 2 months、At 4 months

BIA method - fat mass (grams), lean mass (grams) and total mass (grams).

Phenotypic AgeBaseline、 At 2 months、 At 4 months

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

Spontaneous fluorescence of subcutaneous AGEsBaseline、At 4 months

AGEs test

Carotid thickness of intima mediaBaseline、At 2 months、At 4 months

ultrasound

The levels of MDABaseline、At 2 months、At 4 months

In serum

The levels of GSH-PxBaseline、At 2 months、At 4 months

In serum

The levels of SODBaseline、At 2 months、At 4 months

In serum

Body circumferenceBaseline、At 4 months

Measured with a soft tape - waist, hip, mid-arm, neck and calf circumference

Gait speedBaseline、At 4 months

6m walking time/speed test

The score of the Short Physical Performance Battery (SPPB)Baseline、At 4 months

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.

Time costs of TUGBaseline、At 4 months

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.

Grip strengthBaseline、At 4 months

Calibrated handheld dynamometer.

Pittsburgh sleep quality index (PSQI)Baseline、 At 4 months

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.

Score of Montreal Cognitive Assessment (MoCA)Baseline、At 4 months

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.

The levels of TNF-α in serumBaseline、 At 2 months、 At 4 months

Suspension array

The levels of IL-1 in serumBaseline、 At 2 months、 At 4 months

Suspension array

The levels of IL-6 in serumBaseline、 At 2 months、 At 4 months

Suspension array

The levels of ICAM-1 in serumBaseline、 At 2 months、 At 4 months

Suspension array

T lymphocyte subsetsBaseline、 At 2 months、 At 4 months

CD3+, CD4+, CD8+ were analyzed using flow cytometry

Methylation damageBaseline、 At 4 months

Blood sample

The level of telomere repeat binding factors-1 (TRF-1)Baseline、 At 4 months

Blood sample

Trial Locations

Locations (1)

Talents project team

🇨🇳

Chengdu, Sichuan, China

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