Slow Age: Interventions to Slow Aging in Humans (SlowAge)

Slow Age: a Randomized, Controlled Clinical Trial of Interventions to Slow Aging in Humans

The proportion of older individuals is growing, and it is therefore important to investigate ways to promote healthy aging. Exercise is one of the most studied interventions and is known to have a variety of health benefits. Dietary interventions have also shown encouraging results, with intermittent fasting being a promising anti-aging intervention. Likewise, dietary supplementation with precursors that can increase the central metabolite nicotinamide dinucleotide (NAD+) has powerful effects on aging at least in model organisms. Although physical exercise is known to increase health-span, the effects of these latter dietary interventions on aging lacks evidence in humans.

This is a randomized, controlled trial of interventions to slow aging in humans. Healthy older individuals will be randomized into either an aerobic exercise (EXE), time-restricted feeding (TRF), nicotinamide riboside (NR), or control group and followed for twelve weeks. Changes in biomarkers of aging will be assessed before and after the intervention. It is hypothesized that the interventions provide similar, superior benefits to these markers when compared to placebo.

Primary Outcome: Interleukin-6 levels. Secondary Outcomes: CRP, TNF-α, NAD+, hematologic age, epigenetic age (DNA methylation), transcriptomic age (RNA-sequencing), functional age (handgrip strength, gait speed), body composition, vocal age, and photo age

Study Overview

• Status: Completed
• Conditions: Aging
• Intervention / Treatment: Behavioral: Exercise; Behavioral: Time restricted feeding; Dietary supplement: Nicotinamide riboside

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Morten Scheibye-Knudsen, MD/PhD; Phone Number: 42507060; Email: mscheibye@sund.ku.dk

Study Locations

• Denmark
  • Copenhagen, Denmark, 2200
    • University of Copenhagen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Provision of signed and dated informed consent form
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Aged ≥ 65 years
4. In good general health

Exclusion Criteria:

1. Inability or unwillingness to take oral supplements
2. Inability or unwillingness to adhere to the fasting regiment
3. Inability or unwillingness to perform the prescribed physical exercise
4. Current smoker or use of any nicotine products within 10 years
5. Chronic use of supplements containing vitamin B or nicotinamide riboside
6. Treatment with another investigational drug or other intervention within 1 year
7. Cancer diagnosis within last 5 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exercise arm; 12 week aerobic exercise will be performed in agreement with current guidelines for exercise in older adults from the American College of Sports Medicine. A frequency of 5 days/week, totaling 150-300 min/week, performed at both moderate and vigorous intensities is chosen. This dose has a high level of evidence supporting positive effects on health- and life-span.	Behavioral: Exercise; Participants randomized to the EXE group will perform aerobic exercise five days per week, totaling 150-300 min/week, at moderate to vigorous intensities i.e., ~60-90% heart rate (HR) max. Participants randomized to the EXE group will perform aerobic exercise five days per week, totaling 150-300 min/week, at moderate to vigorous intensities i.e., ~60-90% heart rate (HR) max. Exercise intensity and duration will gradually increase up until week 3 to habituate the participants to the exercise. The training modality will change to reduce the risk of injuries and may be impacted by individual preferences to increase adherence. The training can be performed individually or in groups of 4-6 participants, depending on the geographical locations of the participants home address, and on the current recruitment rate.
Experimental: Time restricted feeding; A 12 week fasting/feeding regiment of 16 hours fasting /8 hours feeding each day is chosen. This ratio has been shown to be tolerable in older individuals.	Behavioral: Time restricted feeding; Participants randomized to the time restricted feeding group will be instructed to abstain from any caloric intake during the targeted fasting window of 16 continuous hours and consume ad libitum during the eating window of 8 hours.
Experimental: Nicotinamide riboside; Previous clinical trials have shown that an nicotinamide riboside dose up to 2 g/day is well tolerated with no treatment-emergent adverse events reported so far and with efficacy on our primary outcome measurement. A dose of 2 g/day NR is therefore chosen and will be split in two: 1 g in the morning and 1 g in the evening.	Dietary supplement: Nicotinamide riboside; Participants randomized to the NR group will be instructed to take the administered tablets once in the morning (1 g) and once in the evening (1 g), in both cases with a meal.
No Intervention: Control; A control group with no intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Interleukin-6 levels in plasma	Day 1 compared to day 84

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of CRP in plasma		Day 1 compared to day 84
Concentration of TNF-α in plasma		Day 1 compared to day 84
Concentration of NAD in whole blood		Day 1 compared to day 84
Change in fat mass	Measured using bio-impedance	Day 1 compared to day 84
Change in lean mass	Measured using bio-impedance	Day 1 compared to day 84
Grip strength		Day 1 compared to day 84
Gait speed	Measured over 4 meters.	Day 1 compared to day 84
Predicted age (DNA methylation)	From PBMCs	Day 1 compared to day 84
Predicted age (Blood age)	From 33 blood parameters	Day 1 compared to day 84
Predicted age (Transcriptomics)	From RNA seq of PBMCs	Day 1 compared to day 84
Predicted age (voice)	From voice recordings	Day 1 compared to day 84
Predicted age (photo)	From a portrait photo	Day 1 compared to day 84

Collaborators and Investigators

• Sponsor: University of Copenhagen
• Collaborators: Elysium Health

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2022
• Primary Completion (Actual): December 21, 2022
• Study Completion (Actual): December 21, 2022

Study Registration Dates

• First Submitted: September 27, 2022
• First Submitted That Met QC Criteria: October 24, 2022
• First Posted (Actual): October 26, 2022

Study Record Updates

• Last Update Posted (Actual): April 25, 2023
• Last Update Submitted That Met QC Criteria: April 24, 2023
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Antimetabolites; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Vitamins; Vitamin B Complex; Nicotinic Acids; Niacinamide; Niacin
• Other Study ID Numbers: H-21017723

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: This is not possible under current data protection rules.

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