Age-dependent metabolic changes in cultured human fibroblasts

Area of Science:

• Cell Biology
• Biochemistry
• Gerontology

Background:

• Cellular energy metabolism, particularly adenosine triphosphate (ATP) production, is crucial for cell function.
• Aging is associated with various cellular dysfunctions, but the underlying metabolic changes are not fully understood.
• Human skin fibroblasts serve as a model to study cellular aging processes in vitro and in vivo.

Purpose of the Study:

• To investigate the impact of metabolic poisons on ATP content in cultured human skin fibroblasts across different ages.
• To assess age-dependent changes in cellular ATP turnover as an indicator of metabolic function.
• To explore the correlation between ATP turnover and age-related functional deficiencies in fibroblasts.

Main Methods:

• Cultured human skin fibroblasts from neonatal and elderly donors were treated with metabolic poisons (potassium cyanide, iodoacetamide, arsenate).
• These poisons inhibit ATP regeneration via glycolysis and oxidative phosphorylation.
• Changes in cellular ATP content following poison exposure were measured to estimate ATP turnover.

Main Results:

• Metabolic poisons induced an age-dependent decrease in cellular ATP content.
• ATP turnover, estimated by the decrease in ATP content after poison exposure, declined with increasing in vitro age (population doubling level).
• Fibroblasts from older donors (68-yr-old) exhibited lower ATP turnover compared to those from neonatal donors.

Conclusions:

• Cellular ATP turnover decreases with cellular aging in human skin fibroblasts.
• This age-related decline in ATP turnover correlates with reduced cell migration capacity, suggesting a metabolic component to age-associated functional deficits.
• Metabolic alterations in ATP production and utilization may contribute to the aging phenotype in skin cells.