Abstract
Cellular senescence has been proposed to play critical roles in tumor suppression and organismal aging, but the molecular mechanism of senescence remains incompletely understood. Here we report that a putative lysosomal carbohydrate efflux transporter, Spinster, induces cellular senescence in human primary fibroblasts. Administration of d-galactose synergistically enhanced Spinster-induced senescence and this synergism required the transporter activity of Spinster. Intracellular d-galactose is metabolized to galactose-1-phosphate by galactokinase. Galactokinase-deficient fibroblasts, which accumulate intracellular d-galactose, displayed increased baseline senescence. Senescence of galactokinase-deficient fibroblasts was further enhanced by d-galactose administration and was diminished by restoration of wild-type galactokinase expression. Silencing galactokinase in normal fibroblasts also induced senescence. These results suggest a role for intracellular galactose in the induction of cellular senescence.
Original language | English (US) |
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Pages (from-to) | 1-4 |
Number of pages | 4 |
Journal | Experimental Gerontology |
Volume | 73 |
DOIs | |
State | Published - Jan 1 2016 |
Keywords
- Galactokinase
- Galactose
- Lysosome
- Senescence
- Spinster
ASJC Scopus subject areas
- Biochemistry
- Aging
- Molecular Biology
- Genetics
- Endocrinology
- Cell Biology