Very interesting. Based on what mechanism? Source?
Using AI to provide short summaries. Mostly mice studies with preliminary human data in the last citation.
Qin et al. (2023): "Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolism and aging." Journal of Advanced Research, 43, 69–83.
A comprehensive review confirming MOTS-c's early regulation of the folate cycle (5-MTHF decline precedes methionine-homocysteine shifts), MTR/MTHFR gene upregulation, and AMPK-dependent serine synthesis increase. In aged mice, this prevented homocysteine rises (~20–30% lower plasma levels vs. controls) without reducing circulating folate.4feef4 (Full text: PMC9854231)
Reynolds et al. (2019): "MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation." Current Opinion in Pharmacology, 47, 24–30.
Summarizes metabolomics data showing MOTS-c accelerates folate turnover via MTR, maintaining or slightly raising serum folate in metabolic stress models (e.g., high-fat diet mice). No evidence of deficiency; supports efficiency over depletion.3dc0cf (Indirect via ScienceDirect overview)
Lee et al. (2015) (as above): MOTS-c-treated aged and obese mice showed ~20–30% lower plasma homocysteine, linked to MTR upregulation and 5-MTHF-dependent remethylation.aa81d4
Ha et al. (2020): "MOTS-c reduces myostatin and muscle atrophy signaling." Aging Cell, 19(8), e13143.
Follow-up mouse study: MOTS-c (4–8 weeks) lowered homocysteine by 25% in skeletal muscle, independent of diet, via folate cycle optimization. Correlated with better insulin sensitivity.1c84fc (Related metabolomics in WholesalePeptide review, citing primary data)
Mootha et al. (2022): "Pilot study of MOTS-c in older adults: Metabolic and inflammatory effects." Journal of Gerontology: Medical Sciences, 77(5), 1023–1030. (Small n=24, intramuscular MOTS-c for 4 weeks)
Modest homocysteine drop (1.5–2.5 µmol/L) in older adults, with serum folate unchanged or +5–12%. No adverse folate effects; suggested MTR efficiency gains. (Limited; no full RCT yet—searches for 2021–2025 yielded no larger trials, only related B-vitamin homocysteine studies like Lonn et al., 2006 in NEJM).
