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Classes

Mitochondrial & longevity

Mitochondria-derived peptides and compounds targeting cellular ageing.

5 compounds in this class. 1 approved by the FDA for at least one indication. 2 have no published human trial data.

Guides in this class

All 5 mitochondrial & longevity compared

CompoundEvidenceReported rangeHalf-lifeStatus
FOXO4-DRI
A senolytic peptide designed to selectively kill senescent cells by disrupting the FOXO4-p53 interaction.
 Animal models only 5-25 mg ~1-2 hours Research only
Glutathione
The principal endogenous intracellular antioxidant, a tripeptide with poor oral bioavailability.
 Clinical trials 200 mg - 2 g ~10 minutes (intravenous) Unapproved
Humanin
The first mitochondrial-derived peptide identified, originally found for its protection against Alzheimer-related neurotoxicity.
 Animal models only 1-5 mg ~30 minutes Research only
MOTS-c
A mitochondria-encoded peptide that acts as an exercise mimetic through AMPK, and one of the better-characterised mitochondrial-derived peptides.
 Preliminary human 5-10 mg ~1-2 hours Research only
SS-31
A cardiolipin-binding tetrapeptide that has been through multiple phase III trials in mitochondrial disease.
 Clinical trials 40-60 mg ~2-4 hours Approved

Head-to-head comparisons

Epitalon vs FOXO4-DRIFOXO4-DRI vs MOTS-cGlutathione vs MOTS-cMOTS-c vs SS-31AICAR vs MOTS-c5-Amino-1MQ vs MOTS-cARA-290 vs SS-31

Mitochondrial & longevity: common questions

What are mitochondrial & longevity?

Mitochondria-derived peptides and compounds targeting cellular ageing. This class has 5 compounds in our directory.

Which mitochondrial & longevity are FDA approved?

SS-31 is FDA approved for at least one indication. The others are not approved.

Which mitochondrial & longevity have the strongest evidence?

By evidence level and number of human studies: Glutathione (clinical trials, ~25 human studies); SS-31 (clinical trials, ~15 human studies); MOTS-c (preliminary human, ~3 human studies).

Can compounding pharmacies make these?

FOXO4-DRI, MOTS-c are not FDA approved and not on the 503A bulks list, so there is no routine legal path to compound them. Material sold online is labelled for research use only. Status checked against FDA lists in October 2026.

References

Regulatory and primary sources

  1. FDA: Bulk drug substances that may present significant safety risks (Category 2 and withdrawn nominations) ↗ · content current as of April 22, 2026; checked October 18, 2026
  2. FDA: Bulk drug substances used in compounding under section 503A ↗ · how the 503A categories work
  3. FDA: Unapproved drugs ↗ · status of products sold "for research use only"
  4. WADA Prohibited List ↗ · peptide hormones and growth factors, class S2
  5. PubMed (National Library of Medicine) ↗ · source of every literature reference on this site

Published literature

  1. van Willigenburg H, de Keizer PLJ, de Bruin RWF. Cellular senescence as a therapeutic target to improve renal transplantation outcome.Pharmacol Res 2018.PubMed 29471104 · doi:10.1016/j.phrs.2018.02.015
  2. Liu BH, Gu YH, Tu Y, et al.. [Molecular regulative mechanisms of aging and interventional effects of Chinese herbal medicine].Zhongguo Zhong Yao Za Zhi 2017.PubMed 29171222 · doi:10.19540/j.cnki.cjcmm.20170731.001
  3. Alameen AAM, Al-Kuraishy HM, Fawzy MN, et al.. Targeting the FOXO4-p53 axis by retro-inverso peptide senolytic agents: a pharmacological strategy to mitigate brain aging and cognitive decline.Naunyn Schmiedebergs Arch Pharmacol 2026.PubMed 42024235 · doi:10.1007/s00210-026-05309-6
  4. Kumar P, Liu C, Suliburk J, et al.. Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial.J Gerontol A Biol Sci Med Sci 2023.PubMed 35975308 · doi:10.1093/gerona/glac135
  5. Aldini G, Altomare A, Baron G, et al.. N-Acetylcysteine as an antioxidant and disulphide breaking agent: the reasons why.Free Radic Res 2018.PubMed 29742938 · doi:10.1080/10715762.2018.1468564
  6. Whalen R, Boyer TD. Human glutathione S-transferases.Semin Liver Dis 1998.PubMed 9875553 · doi:10.1055/s-2007-1007169
  7. Richie JP Jr, Nichenametla S, Neidig W, et al.. Randomized controlled trial of oral glutathione supplementation on body stores of glutathione.Eur J Nutr 2015.PubMed 24791752 · doi:10.1007/s00394-014-0706-z
  8. Lapenna D. Glutathione and glutathione-dependent enzymes: From biochemistry to gerontology and successful aging.Ageing Res Rev 2023.PubMed 37683986 · doi:10.1016/j.arr.2023.102066
  9. Calabrese G, Morgan B, Riemer J. Mitochondrial Glutathione: Regulation and Functions.Antioxid Redox Signal 2017.PubMed 28558477 · doi:10.1089/ars.2017.7121
  10. Duperray J, Sergheraert R, Chalothorn K, et al.. The effects of the oral supplementation of L-Cystine associated with reduced L-Glutathione-GSH on human skin pigmentation: a randomized, double-blinded, benchmark- and placebo-controlled clinical trial.J Cosmet Dermatol 2022.PubMed 33834608 · doi:10.1111/jocd.14137
  11. Fraternale A, Brundu S, Magnani M. Glutathione and glutathione derivatives in immunotherapy.Biol Chem 2017.PubMed 27514076 · doi:10.1515/hsz-2016-0202
  12. Zhang Z, Chen D, Du K, et al.. MOTS-c: A potential anti-pulmonary fibrosis factor derived by mitochondria.Mitochondrion 2023.PubMed 37307934 · doi:10.1016/j.mito.2023.06.002
  13. Mohtashami Z, Singh MK, Salimiaghdam N, et al.. MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases.Int J Mol Sci 2022.PubMed 36233287 · doi:10.3390/ijms231911991
  14. Amado CA, Agüero J, García-Unzueta M, et al.. MOTS-c: How a secreted mitochondrial microprotein may become a potential treatment for inflammatory lung diseases.J Transl Med 2026.PubMed 42243958 · doi:10.1186/s12967-026-08398-2

Literature retrieved from PubMed on October 16, 2026, favouring human studies and reviews. Numbered markers in the text show which paper supports which statement; uncited entries are background reading.