Age-dependent modulation of heparan sulfate structure and function

Area of Science:

• Biochemistry
• Molecular Biology
• Aging Research

Background:

• Heparan sulfate (HS) is crucial for biological processes, mediating interactions with various proteins through its sulfated domains.
• While HS domains are known, the in vivo regulation of their formation remains poorly understood.

Purpose of the Study:

• To investigate how heparan sulfate structure in the human aorta changes with aging.
• To determine the impact of these structural changes on the binding affinity to specific growth factors, particularly platelet-derived growth factor (PDGF).

Main Methods:

• Analysis of heparan sulfate structure from human aorta samples across different age groups.
• Assessment of binding affinities of aged and young aorta HS to specific growth factor isoforms, including PDGF and FGF2.

Main Results:

• Human aorta heparan sulfate structure is progressively modulated during aging.
• Aged HS exhibits significantly enhanced binding to PDGF isoforms, while binding to FGF2 is less affected.
• This enhanced PDGF binding is attributed to an age-dependent increase in GlcN 6-O-sulfation, leading to a higher abundance of specific trisulfated disaccharide units.

Conclusions:

• Aging leads to specific structural modifications in aortic heparan sulfate, altering its interaction profile with growth factors.
• The increased GlcN 6-O-sulfation in aged HS is a key factor driving enhanced PDGF binding.
• These findings provide insights into the regulation of HS structure and function during aging and its implications for growth factor signaling.