NUS releases the PROMETHEUS protocol and pilot results for the first time, detailing a trial that tailors anti-aging supplements to each participant’s “gerotype”
NUS releases the PROMETHEUS protocol and pilot results for the first time, detailing a trial that tailors anti-aging supplements to each participant’s “gerotype”
On 18 September, Professor Andrea Maier presented the protocol and eight-week results from PROMETHEUS, an XPRIZE Healthspan finalist, for the first time at an Academy for Healthy Longevity webinar at the National University of Singapore (NUS). Participants aged 50–80 received the same core program of sleep, nutrition, and exercise. Specific supplements were added only when a participant had a low value for the corresponding aging biomarker, with doses reviewed at week four.
Medical care generally addresses declining organ function when disease is approaching, although that decline begins decades earlier, in young adulthood. Within a person, organs age at different rates: lung function may decline first in one person, muscle function or memory in another. Several years ago, Maier and her colleagues described how genomic, epigenetic, microbiome, and clinical data could be combined into a profile of these differences, a “gerotype.”
In PROMETHEUS, gerotype determines both eligibility and the treatment each participant receives. All 20 participants received the same core program: sleep and nutrition, whey protein, creatine, psychological counseling, and exercise sessions that combined physical activity with cognitive games. Supplements were added only for participants whose relevant aging biomarker fell below the 50th percentile for their age and sex. Urolithin A was given for low muscle strength (it triggers the clearance of damaged mitochondria), nicotinamide mononucleotide for low endurance (the body converts it into NAD+, fuel for mitochondria), and multivitamins for poor performance on a cognitive test. Everyone was reassessed at week four. If there was no response, the dose was increased or the supplement changed, following the same approach used to titrate medication in clinical practice.
Recruitment was limited to people in the bottom 75% for endurance and performance on the NIH Toolbox cognitive test (a standard set of memory and attention tests), deliberately excluding the strongest performers. Maier explained the threshold: “We are all diamonds. It is easier to polish an average diamond than to make an already brilliant stone shine even brighter.” Twenty participants aged 50–80 completed the trial; their average age was 61. More than 80% followed the exercise program and took most of the supplements, and the protocol proved safe.
Over eight weeks, cognitive scores improved significantly and, according to Maier, “more than we expected.” Muscle strength and mass also increased significantly, and visceral fat decreased. Endurance, measured by peak oxygen uptake VO₂, did not change significantly. The ratio of CD4 to CD8 T-cells is one of the markers of immune aging for which geroscience has yet to establish a single reliable standard. This ratio decreased significantly toward the range of 1,5–2 but remained above it.
In August, XPRIZE Healthspan, which has a prize purse of 101 million dollars, announced 20 finalists, including NUS. Grants of 1 million dollars each for coordinated trials went to ten other teams. Maier’s team is preparing a 12-month trial with 180 participants to test whether the pilot’s effects hold at a larger scale. The expanded protocol includes coaching, omega-3, vitamin D, and zinc.
In parallel, Maier is working with a coauthor of the hierarchical outcomes method examined by Ukhvat on a new trial design in which the intervention is adjusted as new measurements become available.