Research Paper Volume 12, Issue 12 pp 12285—12304
Influences of circulatory factors on intervertebral disc aging phenotype
- 1 Department of Orthopaedic Surgery, The First Affiliated Hospital of Jinan University, Guangdong 510630, China
- 2 Ferguson Laboratory for Orthopaedic Research, Department of Orthopaedic Surgery, University of Pittsburgh, E1641 Biomedical Science Tower, Pittsburgh, PA 15213, USA
- 3 Department of Orthopaedic Surgery, Affiliated Hospital of Xiangnan University, Hunan 423000, China
- 4 Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, FL 33410, USA
- 5 Department of Biochemistry, Molecular Biology and Biophysics, The Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN 55455, USA
- 6 Department of Orthopaedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
- 7 Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, PA 15213, USA
- 8 Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA
- 9 Departments of Molecular Pharmacology and Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Received: January 20, 2020 Accepted: April 28, 2020 Published: June 11, 2020
https://doi.org/10.18632/aging.103421How to Cite
Copyright © 2020 Lei et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Whether disc aging is influenced by factors beyond its local environment is an important unresolved question. Here we performed heterochronic parabiosis in mice to study the effects of circulating factors in young and old blood on age-associated intervertebral disc degeneration. Compared to young isochronic pairs (Y-Y), young mice paired with old mice (Y-O) showed significant increases in levels of disc MMP-13 and ADAMTS4, aggrecan fragmentation, and histologic tissue degeneration, but negligible changes in cellular senescence markers (p16INK4a, p21Cip1). Compared to old isochronic pairs (O-O), old mice paired with young mice (O-Y) exhibited a significant decrease in expression of cellular senescence markers (p16, p21, p53), but only marginal decreases in the levels of disc MMP-13 and ADAMTS4, aggrecan fragmentation, and histologic degeneration. Thus, exposing old mice to young blood circulation greatly suppressed disc cellular senescence, but only slightly decreased disc matrix imbalance and degeneration. Conversely, exposing young mice to old blood accelerated their disc matrix imbalance and tissue degeneration, with little effects on disc cellular senescence. Thus, non-cell autonomous effects of circulating factors on disc cellular senescence and matrix homeostasis are complex and suggest that disc matrix homeostasis is modulated by systemic factors and not solely through local disc cellular senescence.