Review
This comprehensive narrative review examines nine therapeutic peptides with proposed applications in healthy aging and age-related conditions: tirzepatide (metabolic dysfunction), epitalon (telomere biology), GHK-Cu (dermal regeneration), BPC-157 and TB-500 (tissue repair), Semax (neuroprotection), CJC-1295 and ipamorelin (growth hormone modulation), and bremelanotide (sexual function). The authors searched PubMed, Scopus, and regulatory databases through January 2026, selecting 20 primary sources based on relevance and methodological quality. The review found that FDA-approved agents such as tirzepatide and bremelanotide have robust safety and efficacy data from large-scale trials, while investigational peptides such as epitalon, BPC-157, and TB-500 show promising signals primarily from preclinical and limited clinical studies. The authors highlight significant knowledge gaps, including the absence of long-term safety data for non-approved peptides, undefined optimal dosing regimens, unknown combination therapy effects, and lack of validated biomarkers for monitoring efficacy. The authors conclude that while therapeutic peptides offer mechanistically diverse approaches to aging hallmarks, investigational agents require rigorous clinical trial validation before clinical adoption. As a narrative review, findings are subject to selection bias and do not represent a quantitative synthesis of evidence.
Frontiers in aging · Apr 2026DOI ↗ Review
This narrative review examines the potential role of therapeutic peptides in orthopaedic care, synthesizing preclinical and mechanistic literature across several peptide classes. The authors categorize peptides by their primary proposed function: wound-healing agents (BPC-157, TB-500, GHK-Cu), growth hormone secretagogues (ipamorelin, CJC-1295, tesamorelin, sermorelin, AOD-9604), recovery-enhancing peptides (epithalon, delta sleep-inducing peptide, pinealon), and neuroactive peptides (selank, semax, dihexa). The review describes how these compounds are theorized to interact with signaling pathways—including PI3K/Akt, mTOR, MAPK, TGF-β, and AMPK—to promote tissue regeneration, resolve inflammation, and support neuromuscular recovery. The authors acknowledge that, while preclinical evidence is promising, robust human clinical trial data are largely absent, representing a significant gap in the literature. Limitations include the review's reliance on animal and in vitro studies, the absence of a systematic search methodology, and the lack of direct clinical evidence supporting efficacy or safety in human orthopaedic populations. The authors call for future controlled trials to validate these mechanistic findings in clinical settings.
Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews · Jan 2026DOI ↗ Review
This review paper synthesizes approximately 25 years of research on Epitalon (also called Epithalon or Epithalone), a synthetic tetrapeptide (Ala-Glu-Asp-Gly, or AEDG) derived from the amino acid composition of Epithalamin, a bovine pineal gland extract. The authors compile findings from in vitro, in vivo, and in silico studies examining Epitalon's biological and pharmacodynamic properties. According to the review, the compound has been associated with geroprotective and neuroendocrine effects, attributed in part to antioxidant, neuroprotective, and antimutagenic mechanisms. Specific findings cited include a reported direct influence on melatonin synthesis, alterations in interleukin-2 mRNA levels, modulation of murine thymocyte mitogenic activity, and enhancement of enzymes such as acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and telomerase. The authors acknowledge that whether these represent the complete mechanisms of action remains uncertain. Notably, the review also highlights that physicochemical and structural investigations of the peptide remain limited relative to the volume of biological research. Key limitations include the predominance of preclinical data and the absence of robust human clinical trial evidence, leaving the translation of these findings to human health outcomes unclear.
International journal of molecular sciences · Mar 2025DOI ↗