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. N-Acetylcysteine (NAC)

   human RCT Direct outcome Not approved for this condition

   Who was studied

   older adults aged 61-80, n=24 randomised (12 to GlyNAC, 8 men and 4 women; 12 to isonitrogenous alanine placebo, 4 men and 8 women), 16 weeks; a separate non-randomised group of 12 young adults aged 21-40 was given the same supplement for 2 weeks

   A 16-week randomised placebo-controlled trial of GlyNAC, meaning glycine and N-acetylcysteine at 100 mg/kg/day each, measured mitochondrial fatty-acid oxidation directly: it rose 78% against placebo (p<0.001), with gait speed up from 1.13 to 1.34 m/s (p=0.032), grip strength improved in both hands (p=0.004) and 6-minute walk distance short of significance (p=0.053). Every arm received the combination and none received N-acetylcysteine alone, so this compound's own contribution cannot be separated from glycine's, and the whole randomised sample is 24 people at one centre. N-acetylcysteine is approved as a mucolytic and as the antidote for paracetamol overdose; neither approval covers ageing or mitochondrial function.

   Source PubMed Central 1 primary source read for this row

2. NAD+ Boosting / Precursor Peptides

   human RCT Direct outcome Not approved for this condition

   Who was studied

   men aged 70-80, median 75, n=12, oral nicotinamide riboside 1 g/day for 21 days with a 21-day washout, randomised double-blind placebo-controlled crossover

   Nicotinamide riboside raised the aged skeletal-muscle NAD+ metabolome as intended and then changed nothing downstream that was measured: complex I- and complex II-supported respiration, maximal respiratory capacity, citrate synthase activity, mitochondrial DNA copy number, mitochondrial resident protein levels and hand-grip strength were all unchanged against placebo. Twelve men for three weeks is small and short, and no longer trial of a NAD+ precursor has measured muscle mitochondrial respiration in older people. A separate 12-week randomised trial of nicotinamide mononucleotide 250 mg/day in men aged 65 and over reported nominal gains in gait speed (p=0.033) and left-hand grip (p=0.019) with no correction for multiple comparisons, and took no respirometry, ATPmax or phosphocreatine measurement at all.

   Source PubMed Central 2 primary sources read for this row

3. SS-31

   human RCT Direct outcome Not approved for this condition

   Who was studied

   healthy community-dwelling older adults aged 60-85, n=39 randomised (19 elamipretide, 20 placebo), 46% female, screened in on muscle ATPmax below 0.7 mM/sec; a single 2-hour intravenous infusion

   A randomised, double-blind, placebo-controlled parallel-group trial infused 0.25 mg/kg/hour for two hours and measured in-vivo muscle mitochondrial capacity (ATPmax) by 31-phosphorus magnetic resonance spectroscopy: ATPmax rose about 27% against 12% on placebo immediately after the infusion (p=0.045 for percent change), and the difference was gone by day 7, while resting mitochondrial coupling (P/O) and fatigue resistance both showed no significant change. This is one dose in one session rather than a treatment course, and no trial of repeated dosing in older adults is on file. The phase 3 programme was in genetic primary mitochondrial myopathy, not ageing: MMPOWER-3 (NCT03323749) randomised 218 people to 40 mg daily subcutaneously for 24 weeks and missed both primary endpoints, and the FDA's September 2025 accelerated approval of elamipretide as Forzinity covers muscle strength in Barth syndrome weighing at least 30 kg, which is a different condition from this one.

   Source PubMed Central 3 primary sources read for this row

4. Humanin

   human observational Mechanistic only Not approved for this condition

   Who was studied

   18 offspring of centenarians against 19 age-matched controls (circulating humanin); 3 people with Alzheimer's disease against 4 controls aged 60-80 (cerebrospinal fluid humanin); 73 newborn cord-blood samples; nobody in any cohort received humanin

   Recorded, and not evidence for this condition

   Every human finding in this paper is an association involving an endogenous humanin concentration: higher circulating humanin in centenarians' offspring, lower cerebrospinal-fluid humanin in Alzheimer's disease, and lower cord-blood humanin where mitochondrial DNA copy number was lower. No study measured mitochondrial function in a person given humanin, because no person has been given it, and a natural blood level tracking age says nothing about what administering the peptide would do. The animal work used HNG, the S14G-humanin analogue rather than humanin itself, and in 18-month-old mice it reduced visceral fat and raised lean mass without extending lifespan.

   Source PubMed Central 1 primary source read for this row

5. MOTS-c

   animal in vivo Mechanistic only Not approved for this condition

   Who was studied

   mice aged 2, 12 and 22 months given MOTS-c 5 or 15 mg/kg/day intraperitoneally for about two weeks, plus a late-life cohort started at 23.5 months and dosed three times weekly; the human part of the same paper was 10 sedentary healthy men aged 24.5 +/- 3.7 who were given nothing

   Recorded, and not evidence for this condition

   In mice, injected MOTS-c improved treadmill running, rotarod performance and grip at every age tested, with old treated animals running roughly twice as long as controls. No human has been administered MOTS-c in any study on file, so no study measured mitochondrial capacity, exercise tolerance or any other endpoint in a person given this peptide; the human evidence is an association between endogenous levels and something else, which is a mechanistic argument rather than a result. A cross-sectional study of 104 healthy men found plasma MOTS-c about 21% lower in the 70-81 group than the 18-30 group, but muscle MOTS-c was higher in the older men, not lower, which runs opposite to the decline the peptide is sold to correct.

   Source PubMed Central 2 primary sources read for this row

6. Epitalon

   in vitro Mechanistic only Not approved for this condition

   Who was studied

   cultured human pineal gland cells taken through replicative senescence; no living human or animal subject

   Recorded, and not evidence for this condition

   Confocal laser scanning microscopy of senescing human pinealocyte cultures found that AEDG, the tetrapeptide sold as epitalon, increased the stained area of MitoTracker Red by about 1.5-fold and lowered ribosomal protein L7A expression by 22%. A dye-stained area in a cell culture is not mitochondrial capacity, and no study measured mitochondrial function, exercise tolerance or any other ageing endpoint in a living person given epitalon. The long-running Russian geroprotection reports that are usually cited for this peptide, including the 15-year follow-up in 79 coronary patients and the melatonin-rhythm work in elderly subjects, both used epithalamin, a bovine pineal gland extract, and not the synthetic AEDG tetrapeptide.

   Source PubMed 3 primary sources read for this row

Recorded absences

5 compounds are 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. FOXO4-DRI

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

   The record is one 2017 paper in Cell. A designed FOXO4 peptide disrupted the FOXO4-p53 interaction, selectively killed senescent cells, and in naturally aged and XpdTTD/TTD fast-ageing mice restored running-wheel fitness, fur density and renal function. Nothing mitochondrial was measured in it, no ageing endpoint has been measured in any human given FOXO4-DRI, and a healthspan result in a mouse is not a human claim, so this row records an absence rather than a rung.

2. GHRH (Growth Hormone-Releasing Hormone)

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

   No trial has used this compound against this condition; no mitochondrial endpoint was measured in any retrieved GHRH study.

3. GHRP-1

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

   No trial has used this compound against this condition; no mitochondrial or ageing endpoint was measured.

4. Glutathione

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

   Glutathione is the deficiency these ageing studies report, not the substance they administer. In the 16-week GlyNAC trial in adults aged 61-80, red-cell glutathione was an outcome and glycine plus N-acetylcysteine were the intervention; a glutathione level corrected by giving its precursors is not evidence about giving glutathione. No trial located here administered glutathione itself, by any route, and then measured mitochondrial function in older adults, so this row records an absence rather than a rung.

5. NAD+

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

   NAD+ is the molecule these ageing studies measure, not usually the one they administer; the muscle and function trials give precursors such as nicotinamide riboside or nicotinamide mononucleotide instead. The only located human study of NAD+ given directly is a pilot 6-hour intravenous infusion of 750 mg in 11 men aged 30-55, which tracked plasma and urine NAD+ metabolites and took no mitochondrial, muscle or functional measurement whatever, and enrolled nobody old. No controlled trial of intravenous NAD+ with a mitochondrial endpoint in older adults is on file, so this row records an absence rather than a rung.

Checked, and nothing recorded

17 compounds were checked against age related mitochondrial dysfunction and produced no gradeable row.

• Anserine — checked, no row on file
• Balenine — checked, no row on file
• Carnosine — checked, no row on file
• Elastin Peptides — checked, no row on file
• GHK-Cu — checked, no row on file
• Hexapeptide-11 — checked, no row on file
• Hexapeptide-9 — checked, no row on file
• L-Carnitine — checked, no row on file
• Palmitoyl Hexapeptide-12 — checked, no row on file
• Palmitoyl Tetrapeptide-7 — checked, no row on file
• Palmitoyl Tripeptide-38 — checked, no row on file
• Pinealon — checked, no row on file
• Silk Peptides — checked, no row on file
• Soy Peptides — checked, no row on file
• Tetrapeptide-30 — 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.