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Aging affects epidermal growth factor receptor phosphorylation and traffic kinetics
W R Reenstra1, M Yaar, B A Gilchrest
1Department of Dermatology, Boston University School of Medicine, Massachusetts 02118-2394, USA.
Experimental Cell Research
|September 15, 1996
Summary
Aging human fibroblasts show delayed epidermal growth factor receptor (EGFR) phosphorylation and impaired receptor trafficking. These changes in EGFR activation and processing contribute to reduced cellular responsiveness in older individuals.
Area of Science:
- Cellular biology
- Gerontology
- Molecular signaling
Background:
- Cultured human fibroblasts exhibit reduced epidermal growth factor receptors (EGFRs) and mitogenic response with increasing donor age.
- Understanding age-related changes in EGFR phosphorylation and trafficking is crucial for explaining decreased cellular responsiveness.
Purpose of the Study:
- To investigate age-associated differences in epidermal growth factor receptor (EGFR) autophosphorylation and trafficking kinetics in human fibroblasts.
- To elucidate the impact of aging on EGFR activation and processing following ligand binding.
Main Methods:
- Fibroblasts from donors of varying ages were utilized.
- Analysis of epidermal growth factor receptor (EGFR) autophosphorylation after ligand stimulation.
- Assessment of receptor-ligand complex trafficking and clearance from the plasma membrane.
Main Results:
- An age-associated delay in the rate of EGFR phosphorylation was observed post-epidermal growth factor stimulation.
- Aging significantly affected receptor/ligand trafficking, showing decreased and delayed intracellular transport.
- A slower rate of clearance of occupied receptors from the plasma membrane was noted in older fibroblasts.
Conclusions:
- Aging impairs epidermal growth factor receptor (EGFR) activation and processing in human fibroblasts.
- Decrements in EGFR activation and processing contribute to the age-associated decline in cellular mitogenic response.