Oxidative stress-induced senescence markedly increases disc cell bioenergetics.

Authors:
Prashanti Patil
Prashanti Patil
University of Pittsburgh
Pittsburgh | United States
Micol Falabella
Micol Falabella
Delhi University
India
Amal Saeed
Amal Saeed
University of Tübingen
Germany
Brett Kaufman
Brett Kaufman
Center for Metabolism and Mitochondrial Medicine
Pittsburgh | United States
Sruti Shiva
Sruti Shiva
University of Pittsburgh
United States
Claudette St Croix
Claudette St Croix
University of Pittsburgh
United States

Mech Ageing Dev 2019 Jun 17;180:97-106. Epub 2019 Apr 17.

Department of Orthopedic Surgery, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA, 15213, USA; Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, 15213, USA. Electronic address:

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.

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Source
https://linkinghub.elsevier.com/retrieve/pii/S00476374183019
Publisher Site
http://dx.doi.org/10.1016/j.mad.2019.04.006DOI Listing
June 2019
11 Reads
3.397 Impact Factor

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