Oxidative stress-induced senescence markedly increases disc cell bioenergetics

Prashanti Patil, Micol Falabella, Amal Saeed, Dayeong Lee, Brett Kaufman, Sruti Shiva, Claudette St Croix, Ben Van Houten, Laura J. Niedernhofer, Paul D. Robbins, Joon Lee, Sowa Gwendolyn, Nam V. Vo

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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 languageEnglish (US)
Pages (from-to)97-106
Number of pages10
JournalMechanisms of Ageing and Development
Volume180
DOIs
StatePublished - 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

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