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Age-dependent metabolic changes in cultured human fibroblasts
Abstract:
The effects of metabolic poisons on the ATP content of cultured human skin fibroblasts at selected in vitro and in vivo ages were studied. Potassium cyanide, iodacetamide, and Arsenate were used to inhibit ATP restoration by glycolysis and oxidative phosphorylation. Cells treated with these metabolic poisons showed an age-dependent change in their ATP content. The decrease in cellular ATP content after exposure to these drugs was taken as an estimate of ATP turnover. It was found that there was a decrease in the ATP turnover with increasing population doubling level (i.e. in vitro age), and cells cultured from a 68-yr-old donor had a lower ATP turnover than those cultured from a neonatal donor. This decreased ATP turnover correlates with a previous finding of a decreased ability of "older" cells to be stimulated to migrate in culture and suggests that there is a metabolic component to this age-related functional deficiency.
Insights
Metabolic poisons reveal age-related changes in human skin fibroblast ATP content. Cellular ATP turnover decreases with aging, suggesting a metabolic basis for age-related functional decline in skin cells.
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.