The collagen-derived compound collagen tripeptide induces collagen expression and extends lifespan via a conserved p38 mitogen-activated protein kinase cascade

Biochem Biophys Res Commun. 2018 Nov 10;505(4):1168-1173. doi: 10.1016/j.bbrc.2018.10.044. Epub 2018 Oct 12.

Abstract

The skin consists mostly of extracellular matrix (ECM) composed mainly of collagen, which provides a protective barrier from the environment. The skin continuously experiences harmful stress and damage. As aging progresses, the expression of various genes declines, and physiological functional deterioration occurs. The reduction of collagen accompanying aging impairs the barrier function of the skin and weakens protection from stressors. In the nematode Caenorhabditis elegans, ECM proteins turn over during aging. Older worms of longevity mutants exhibit increased collagen expression, whereas knockdown of collagen genes shortens lifespan. However, it is unclear whether the progression of aging can be delayed by increasing collagen production via an external stimulus. In this study, we examined the effects of collagen tripeptide (CTP), a collagen-derived compound, on lifespan and aging. Our results showed that CTP upregulated collagen genes via the p38 mitogen-activated protein kinase (MAPK)/SKN-1 pathway. Moreover, CTP extended lifespan and delayed aging through p38 MAPK/SKN-1 pathway. In addition, CTP also induced collagen expression via the p38 MAPK pathway in mammals. Our findings supported that external stimuli such as CTP could promote ECM youthfulness using a conserved signaling pathway, thereby contributing to suppression of aging.

Keywords: Aging; Collagen synthesis; Collagen tripeptide; Extracellular matrix; Mitogen-activated protein kinase; Skin.

MeSH terms

  • Aging / drug effects
  • Animals
  • Caenorhabditis elegans / enzymology
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / metabolism
  • Collagen / biosynthesis*
  • Collagen / chemistry
  • Collagen / genetics
  • DNA-Binding Proteins / metabolism
  • HeLa Cells
  • Humans
  • Longevity / drug effects*
  • MAP Kinase Signaling System / drug effects*
  • Peptides / pharmacology*
  • Transcription Factors / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • Peptides
  • Transcription Factors
  • skn-1 protein, C elegans
  • Collagen
  • p38 Mitogen-Activated Protein Kinases