Compounds with a graded row

Ordered by rung, strongest first. The rung rates the study design; the chip beside it says what the study measured. Both are needed.

1. NAD+ Boosting / Precursor Peptides

   human RCT Direct outcome Not approved for this condition

   Who was studied

   adults with mild cognitive impairment, n=20 randomised 1:1 (nicotinamide riboside arm 5 men and 5 women, mean age 77.1, range 71-83; placebo arm 2 men and 8 women, mean age 75.2, range 67-86), oral nicotinamide riboside 1 g/day for 10 weeks

   DNA methylation in peripheral blood mononuclear cells was an exploratory outcome of a safety-focused pilot, and the four clocks disagreed with each other: PhenoAge and GrimAge showed a subtle decrease in paired mean difference on nicotinamide riboside, the Hannum-based extrinsic measure showed markers of accelerated ageing on treatment and not on placebo, and the Horvath-based intrinsic measure showed no difference between groups. The authors state the analysis was not corrected for multiple comparisons and that the study was not powered to detect methylation changes. Blood NAD+ rose 2.6-fold, confirming the dose was delivered; the primary endpoint was the Montreal Cognitive Assessment, which did not change, and no trial has been designed with an epigenetic clock as its primary outcome.

   Source PubMed Central 1 primary source read for this row

2. DHEA

   human case series Direct outcome Not approved for this condition

   Who was studied

   men aged 51-65, n=10 enrolled and 9 completed, DHEA 50 mg three to four times weekly from week 2 as one part of a five-agent combination, open-label with no control group, 12 months

   DHEA appears in this literature only as one component of the TRIIM combination, taken with recombinant human growth hormone, metformin 500 mg, vitamin D3 and zinc for a year. Mean epigenetic age across the Horvath, Hannum, PhenoAge and GrimAge clocks fell about 2.5 years against the expected chronological trajectory, but the study was open-label with no control arm, and DHEA was never administered by itself, so nothing here separates its effect from growth hormone's or metformin's. No trial of DHEA alone has measured any named epigenetic clock in this population.

   Source PubMed Central 1 primary source read for this row

3. hGH

   human case series Direct outcome Not approved for this condition

   Who was studied

   men aged 51-65, n=10 enrolled and 9 completed, open-label with no control group and no randomisation, 12 months of treatment with measurements to 18 months

   The TRIIM study is the only human work on file in which any compound in this corpus was measured against named epigenetic clocks. Nine men completed a year of recombinant human growth hormone, starting at 0.015 mg/kg three to four times weekly, given alongside DHEA 50 mg, metformin 500 mg, vitamin D3 3,000 IU and zinc 50 mg; mean epigenetic age across the Horvath, Hannum, PhenoAge and GrimAge clocks fell about 2.5 years against the expected chronological trajectory, and the GrimAge decrease of roughly 2 years was still present six months after treatment stopped. There was no control arm, no randomisation and no blinding, the comparison is against expected ageing rather than against untreated people, growth hormone was never given alone beyond a three-week sequencing period so its own contribution cannot be separated, and several authors held shares or share options in the sponsoring company.

   Source PubMed Central 1 primary source read for this row

Recorded absences

1 compound is listed here without a rung. Each row exists to mark a distinction a reader would otherwise draw wrongly, and each says what is missing rather than leaving the compound off the page.

1. Epitalon

   No rung — nothing on file to grade Not approved for this condition

   Epitalon is the peptide most often sold on a longevity claim, and the result usually cited for it is telomerase rather than methylation: a 2003 in-vitro study added the peptide to telomerase-negative human fetal fibroblast culture and reported telomerase expression and telomere elongation. Telomere length and epigenetic age are different measurements and neither stands in for the other. No study on file has measured Horvath, Hannum, PhenoAge, GrimAge or any other named clock in a person given epitalon, so this row records an absence rather than a rung.

Checked, and nothing recorded

13 compounds were checked against epigenetic age acceleration and produced no gradeable row.

• Anserine — checked, no row on file
• Balenine — checked, no row on file
• Carnosine — checked, no row on file
• FOXO4-DRI — checked, no row on file
• GHK-Cu — checked, no row on file
• Glutathione — checked, no row on file
• Humanin — checked, no row on file
• MOTS-c — checked, no row on file
• N-Acetylcysteine (NAC) — checked, no row on file
• NAD+ — checked, no row on file
• SS-31 — checked, no row on file
• Thymalin — checked, no row on file
• Thymulin — checked, no row on file

A compound is here because someone looked and the sources did not support a row — not because nobody looked. Under the rubric, uncertainty resolves to no row, and a row resting on a vendor page or a clinic blog is worse than no row at all.