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Humanin with MOTS-c

Mechanism-tag overlap and published literature for Humanin and MOTS-c, pulled verbatim from each Kalios compound profile. Kalios is a literature reference, not a recommendation.

Mechanism overlap

Mechanism tags are verbatim labels on each compound's profile. Generic tags ("peptide", "small-molecule", "research-chemical") are excluded from this overlap view. Tags are descriptive — not an inference about combined effect.

HUMANIN MOTS-C 2 UNIQUE TAGS 1 UNIQUE TAGS 0 SHARED
Humanin unique mdpmitochondrial-derived-peptide
Shared none
MOTS-c unique mitochondrial-derived-exercise-mimetic

Co-administration notes from the literature

Verbatim summary text pulled from each compound's profile data. Researchers studying Humanin and MOTS-c have published these mechanism-level observations. Not a co-administration recommendation.

Evidence level: mechanistic only

MOTS-c is the second identified MDP (encoded in the mitochondrial 12S rRNA ORF) with primary effects on metabolic regulation, AMPK activation, and exercise-mimetic signaling. Combining humanin (broad cytoprotection, neuroprotection, anti-apoptotic) with MOTS-c (metabolic optimization, mitochondrial biogenesis) addresses complementary aspects of mitochondrial-retrograde signaling. Both decline with age and are elevated in long-lived human cohorts — the mechanistic rationale for co-supplementation is sound, though human evidence for the combination is absent.

Quick facts

Humanin

RouteSubQ / IV / intranasal (research)
Half-lifeNot listed
FDA statusNot approved; research only
WADANot listed
Full Humanin profile →

MOTS-c

RouteSubQ / IP / IM
Half-life~2 hr plasma; hours-days tissue
FDA statusNot approved
WADANot listed
Full MOTS-c profile →

Literature table

Classified references from each compound profile. Click a column header to sort. Click a PMID to open PubMed. Findings are quoted verbatim from each profile's literature_summary; nothing here is added or interpreted.

Year Compound Source Finding
2011HumaninOh YK, Bachar AR, Zacharias DG, Kim SG, Wan J, Cobb LJ, Lerman LO, Cohen P, Lerman A. Humanin preserves endothelial function and prevents atherosclerotic plaque progression in hypercholesterolemic ApoE deficient mice. Atherosclerosis. 2011;219(1):65-73. PMID: 21641599. PMID 21641599preclinical, in vivo
2010HumaninMuzumdar RH, Huffman DM, Calvert JW, Jha S, Weinberg Y, Cui L, Nemkal A, Atzmon G, Klein L, Gundewar S, Ji SY, Lavu M, Predmore BL, Lefer DJ. Acute humanin therapy attenuates myocardial ischemia and reperfusion injury in mice. Arterioscler Thromb Vasc Biol. 2010;30(10):1940-1948… PMID 20689081preclinical, in vivo
2002HumaninTajima H, Niikura T, Hashimoto Y, Ito Y, Kita Y, Terashita K, Yamazaki K, Koto A, Aiso S, Nishimoto I. Evidence for in vivo production of humanin peptide, a neuroprotective factor against Alzheimer's disease-related insults. Neurosci Lett. 2002;324(3):227-231. PMID: 12021353. (I… PMID 12021353preclinical, in vivo
2009HumaninHashimoto Y, Kurita M, Aiso S, Nishimoto I, Matsuoka M. Humanin inhibits neuronal cell death by interacting with a cytokine receptor complex or complexes involving CNTF receptor alpha/WSX-1/gp130. Mol Biol Cell. 2009;20(12):2864-2873. PMID: 19509334. (Trimeric receptor complex c… PMID 19509334mechanism / discovery
2001HumaninHashimoto Y, Niikura T, Tajima H, Yasukawa T, Sudo H, Ito Y, Kita Y, Kawasumi M, Kouyama K, Doyu M, Sobue G, Koide T, Tsuji S, Lang J, Kurokawa K, Nishimoto I. A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Abeta. Proc… PMID 11371643mechanism / discovery
2001HumaninHashimoto Y, Ito Y, Niikura T, Shao Z, Hata M, Oyama F, Nishimoto I. Mechanisms of neuroprotection by a novel rescue factor humanin from Swedish mutant amyloid precursor protein. Biochem Biophys Res Commun. 2001;283(2):460-468. PMID: 11327724. (Early mechanism paper, HNG potency… PMID 11327724mechanism / discovery
2019HumaninConte M, Ostan R, Fabbri C, Santoro A, Guidarelli G, Vitale G, Mari D, Sevini F, Capri M, Sandri M, Monti D, Franceschi C, Salvioli S. Human aging and longevity are characterized by high levels of mitokines. J Gerontol A Biol Sci Med Sci. 2019;74(5):600-607. PMID: 29420698. (Hum… PMID 29420698research article
2018HumaninGong Z, Tas E, Muzumdar R. Humanin and age-related diseases: a new therapeutic target? World J Diabetes. 2018;9(8):141-146. PMID: 30159123. PMID 30159123research article
2017HumaninKim SJ, Xiao J, Wan J, Cohen P, Yen K. Mitochondrially derived peptides as novel regulators of metabolism. J Physiol. 2017;595(21):6613-6621. PMID: 28574175. PMID 28574175research article
2017HumaninNashine S, Cohen P, Chwa M, Lu S, Nesburn AB, Kuppermann BD, Kenney MC. Humanin G (HNG) protects age-related macular degeneration (AMD) transmitochondrial ARPE-19 cybrids from mitochondrial and cellular damage. Cell Death Dis. 2017;8(7):e2951. PMID: 28726778. PMID 28726778research article
2015HumaninLee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, Kim SJ, Mehta H, Hevener AL, de Cabo R, Cohen P. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015;21(3):443-454. PMID: 25738459. (MOTS-… PMID 25738459research article
2013HumaninLee C, Yen K, Cohen P. Humanin: a harbinger of mitochondrial-derived peptides? Trends Endocrinol Metab. 2013;24(5):222-228. PMID: 23402768. (Framing of humanin within MDP class.) PMID 23402768research article
2022MOTS-cRamanjaneya M, Jerobin J, Bettahi I, et al. MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases. Int J Mol Sci. 2022;23(19):11991. PMID: 36233287. PMID 36233287human study
2022MOTS-cYin X, Jing Y, Chen Q, et al. The intraocular expression of MOTS-c in patients with age-related cataracts: Correlation between MOTS-c and lens mitochondrial DNA levels. Clin Exp Ophthalmol. 2022;50(5):498-506.human study
2018MOTS-cKim KH, Son JM, Benayoun BA, Lee C. The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress. Cell Metab. 2018;28(3):516-524.e7. PMID: 29983246. PMID 29983246mechanism / discovery
2023MOTS-cKong BS, Lee C, Cho YM. Mitochondrial-encoded peptide MOTS-c, diabetes, and aging-related diseases. Diabetes Metab J. 2023;47(3):315-327. PMID: 36672073. PMID 36672073research article
2021MOTS-cReynolds JC, Lai RW, Woodhead JST, Joly JH, Mitchell CJ, Cameron-Smith D, Lu R, Cohen P, Graham NA, Benayoun BA, Merry TL, Lee C. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun. 2021;12(1):470. P… PMID 33473109research article
2018MOTS-cMendelsohn AR, Larrick JW. Mitochondrial-Derived Peptides Exacerbate Senescence. Rejuvenation Res. 2018;21(4):369-373. PMID: 30037300. PMID 30037300research article

Related pair pages

More research context

Frequently asked

Have Humanin and MOTS-c been studied together?

Researchers have published mechanistic-level co-administration discussion of Humanin and MOTS-c. No human co-administration trials are catalogued in the Kalios profiles. The pair page lists each compound's classified literature; full citations sit on each individual profile.

What mechanisms do Humanin and MOTS-c share?

Humanin and MOTS-c do not share a specific mechanism tag on their Kalios profiles. They appear on the same pair page because at least one profile lists the other in its co-administration data.

What is the FDA status of Humanin and MOTS-c?

Humanin: Not approved; research only. MOTS-c: Not approved. FDA-status text is pulled verbatim from each compound profile. See /fda-pcac-2026.html for the broader FDA Pharmacy Compounding Advisory Committee context.

Where can I find the full research on Humanin and MOTS-c?

Full citation lists, dosing tables from the literature, reconstitution data, and the FDA / WADA status are on the individual compound profiles: the Humanin profile and the MOTS-c profile. The Kalios Stack Research Tool hub lists every compound covered.

Last updated: April 2026