SHLP (Small Humanin-Like Peptides)

Small Humanin-Like Peptides (SHLPs) comprise a family of six mitochondrial-derived peptides (SHLP1-6) encoded within the 16S ribosomal RNA region of the mitochondrial genome, the same region encoding humanin. Like humanin, these peptides represent a class of retrograde signals through which mitochondria communicate metabolic status to the cell and organism.

Among the family members, SHLP2 and SHLP6 have received the most research attention. SHLP2 demonstrates potent effects on insulin sensitivity and glucose homeostasis, functioning as a metabolic regulator that improves cellular energy metabolism. SHLP6, in contrast, appears to have pro-apoptotic effects, suggesting complex regulatory roles within the family.

The SHLPs extend the concept of mitochondrial-derived peptides beyond humanin and MOTS-c, revealing the mitochondrial genome as a source of diverse signaling molecules with distinct but complementary functions in cellular homeostasis, metabolism, and stress responses.

Research indicates SHLP2 administration improves metabolic parameters in animal models, enhances mitochondrial function, and provides cytoprotection against various stressors. The age-related decline in SHLP levels, paralleling the decline in humanin and MOTS-c, suggests these peptides may collectively contribute to metabolic aspects of aging, making them candidates for longevity research interventions.