SHLP6

also known as: Small humanin-like peptide 6, MT-RNR2-derived SHLP6

A SHLP-family member with a notably distinct preclinical profile: where humanin and SHLP2 are antiapoptotic, SHLP6 has been reported as pro-apoptotic, suggesting the mitochondrial-derived peptide family includes members with opposing regulatory roles. Research-only.

A mitochondrial-derived peptide in the SHLP1–SHLP6 family. Notably distinct from humanin, SHLP2, and MOTS-c in its reported pro-apoptotic effect in multiple cell-culture models, suggesting that the broader mitochondrial-derived peptide family includes members with opposing regulatory roles rather than all acting as uniformly cytoprotective. Research-only; no clinical development.

Mechanism of action

Proposed pro-apoptotic activity — contrasting with humanin, SHLP2, and MOTS-c. The biological significance of this is debated; one hypothesis is that SHLP6 represents an "off-switch" balancing the prosurvival effects of other mitochondrial-derived peptides. Molecular target and receptor engagement are not established.

Primary uses

Mitochondrial-derived peptide biology research (preclinical)
Apoptosis-regulation research (cell culture)

Typical dosing

Not established for human use

⚠ No human dosing established. Any human use would be unregulated and unsupported.

Regulatory status

Not FDA-approved. Research-only. No registered clinical trials.

References

[pubmed] Cobb LJ, et al. "Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers." Aging (Albany NY), 2016;8:796-809.
[pubmed] Mehta HH, et al. "Mitochondrial-derived peptides as biomarkers of aging and age-related diseases." Aging Cell, 2022;21:e13641.

Related peptides

Humanin

A mitochondrial-derived peptide with neuroprotective, metabolic, and anti-apoptotic activity — one of the first signaling peptides identified as encoded by mitochondrial DNA.

SHLP2

A 26-aa mitochondrial-derived peptide, the most-studied of the SHLP1–SHLP6 family (Cohen lab, USC). Preclinical data report insulin-sensitizing, antiapoptotic, and metabolic-protective effects; lower plasma levels in humans correlate with age and with type 2 diabetes. Research-only; no human clinical trials.

SHLP3

One of the six small humanin-like peptides (Cohen lab); preclinical reports suggest roles in adipogenesis and metabolic regulation. Less well-characterized than SHLP2 or humanin. Research-only.

Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.