GHK-Cu · research summary

Middle-aged mice treated with GHK-Cu peptide administered intraperitoneally or intranasally show behavioral rescue but divergent hippocampal aging programs.

Research square · 2026. Summary drawn from the study's full text. Each statement is followed by the exact sentence it comes from. This is a research summary, not medical advice.

Study type

Preclinical animal study using aged mice to evaluate GHK-Cu effects on cognitive aging via different administration routes.
“Aged C57BL/6J mice (20–21 months) received GHK-Cu (15 mg/kg) via short-term intraperitoneal (IP; 5 days) or longer-term intranasal (IN; 8 weeks) administration.”

Subjects

Aged C57BL/6J mice, both male and female, aged 20-21 months.
“Aged C57BL/6J mice (20–21 months) received GHK-Cu (15 mg/kg) via short-term intraperitoneal (IP; 5 days) or longer-term intranasal (IN; 8 weeks) administration.”

Sample size

50 male and 50 female mice were obtained and randomized to treatment paradigms.
“C57BL/6J mice (50 male, 50 female), 18 months of age, were obtained from the National Institute on Aging Aged Rodent Colony (Charles River Laboratories) and housed under specific pathogen-free conditions (14:10-hour light-dark cycle, ad libitum food and water) at the University of Washington.”

Duration

Short-term intraperitoneal administration for 5 days or longer-term intranasal administration for 8 weeks.
“Aged C57BL/6J mice (20–21 months) received GHK-Cu (15 mg/kg) via short-term intraperitoneal (IP; 5 days) or longer-term intranasal (IN; 8 weeks) administration.”

Reported findings

Intranasal treatment induced suppression of oxidative phosphorylation and MYC target pathways, whereas intraperitoneal treatment activated these pathways.
“IN GHK-Cu induced coordinated suppression of oxidative phosphorylation (male NES − 5.44, female NES − 4.20; FDR < 0.0001) and MYC target pathways (female NES − 4.31, FDR < 0.0001), with additional attenuation of PI3K-AKT-mTOR signaling in females (NES − 3.15, FDR = 0.062).”
Intraperitoneal treatment activated DNA repair and stress-response pathways, contrasting with the metabolic suppression seen with intranasal delivery.
“In contrast, IP treatment activated oxidative phosphorylation (female NES 4.97, FDR < 0.001), DNA repair (NES 5.58, FDR < 0.001), and MYC targets (NES 4.34, FDR = 0.002), indicating engagement of acute stress-response and repair pathways.”

Limitations stated by the authors

Bulk RNA sequencing cannot resolve cell-type-specific transcriptional changes and may reflect shifts in cellular composition.
“First, bulk RNA sequencing cannot resolve cell-type-specific transcriptional changes and may reflect shifts in cellular composition [31–32].”
Pharmacokinetic measurements of brain GHK-Cu concentrations were not performed.
“Second, pharmacokinetic measurements of brain GHK-Cu concentrations were not performed, limiting interpretation of route-dependent exposure differences [19, 35].”
Transcriptomic profiling was conducted at a single time point, precluding evaluation of temporal dynamics.
“Third, transcriptomic profiling was conducted at a single time point, precluding evaluation of temporal dynamics in molecular responses.”

Source: PubMed 42245779 · DOI 10.21203/rs.3.rs-9520102/v1 · all study summaries

Sample size

50 male and 50 female mice were obtained and randomized to treatment paradigms.

“C57BL/6J mice (50 male, 50 female), 18 months of age, were obtained from the National Institute on Aging Aged Rodent Colony (Charles River Laboratories) and housed under specific pathogen-free conditions (14:10-hour light-dark cycle, ad libitum food and water) at the University of Washington.”

Reported findings

Intranasal treatment induced suppression of oxidative phosphorylation and MYC target pathways, whereas intraperitoneal treatment activated these pathways.

“IN GHK-Cu induced coordinated suppression of oxidative phosphorylation (male NES − 5.44, female NES − 4.20; FDR < 0.0001) and MYC target pathways (female NES − 4.31, FDR < 0.0001), with additional attenuation of PI3K-AKT-mTOR signaling in females (NES − 3.15, FDR = 0.062).”

Intraperitoneal treatment activated DNA repair and stress-response pathways, contrasting with the metabolic suppression seen with intranasal delivery.

“In contrast, IP treatment activated oxidative phosphorylation (female NES 4.97, FDR < 0.001), DNA repair (NES 5.58, FDR < 0.001), and MYC targets (NES 4.34, FDR = 0.002), indicating engagement of acute stress-response and repair pathways.”

Limitations stated by the authors

Bulk RNA sequencing cannot resolve cell-type-specific transcriptional changes and may reflect shifts in cellular composition.

“First, bulk RNA sequencing cannot resolve cell-type-specific transcriptional changes and may reflect shifts in cellular composition [31–32].”

Pharmacokinetic measurements of brain GHK-Cu concentrations were not performed.

“Second, pharmacokinetic measurements of brain GHK-Cu concentrations were not performed, limiting interpretation of route-dependent exposure differences [19, 35].”

Transcriptomic profiling was conducted at a single time point, precluding evaluation of temporal dynamics.

“Third, transcriptomic profiling was conducted at a single time point, precluding evaluation of temporal dynamics in molecular responses.”