Abstract
Cellular senescence is a phenotype characterized by irreversible growth arrest, chronic elevated secretion of proinflammatory cytokines and matrix proteases, a phenomenon known as senescence-associated secretory phenotype (SASP). Biomarkers of cellular senescence have been shown to increase with age and degeneration of human disc tissue. Senescent disc cells in culture recapitulate features associated with age-related disc degeneration, including increased secretion of proinflammatory cytokines, matrix proteases, and fragmentation of matrix proteins. However, little is known of the metabolic changes that underlie the senescent phenotype of disc cells. To assess the metabolic changes, we performed a bioenergetic analysis of in vitro oxidative stress-induced senescent (SIS)human disc cells. SIS disc cells acquire SASP and exhibit significantly elevated mitochondrial content and mitochondrial ATP-linked respiration. The metabolic changes appear to be driven by the upregulated protein secretion in SIS cells as abrogation of protein synthesis using cycloheximide decreased mitochondrial ATP-linked respiration. Taken together, the results of the study suggest that the increased energy generation state supports the secretion of senescent associated proteins in SIS disc cells.
Original language | English (US) |
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Pages (from-to) | 97-106 |
Number of pages | 10 |
Journal | Mechanisms of Ageing and Development |
Volume | 180 |
DOIs | |
State | Published - Jun 2019 |
Bibliographical note
Funding Information:The work was supported by the National Institute of Health ( AG044376 to NV, GM110424 to BAK and MF, AG043376 and AG056278 to PDR and LJN, and 1S10RR019003-01 Shared Instrument Grant). We would like to acknowledge the NIH supported microscopy resources in the Center for Biologic Imaging. Specifically the confocal microscope supported by grant number 1S10OD019973-01.
Funding Information:
The work was supported by the National Institute of Health (AG044376 to NV, GM110424 to BAK and MF, AG043376 and AG056278 to PDR and LJN, and 1S10RR019003-01 Shared Instrument Grant). We would like to acknowledge the NIH supported microscopy resources in the Center for Biologic Imaging. Specifically the confocal microscope supported by grant number 1S10OD019973-01. We would like to thank Catherine Corey for help with running the Seahorse extracellular flux assays and Jessa Darwin for editorial support.
Publisher Copyright:
© 2019
Keywords
- Aging
- Bioenergetics
- Cellular senescence
- Intervertebral disc degeneration
- Matrix homeostasis
- Mitochondria