title: Molecular mechanisms of biological aging in intervertebral discs.
abstract: Advanced age is the greatest risk factor for the majority of human ailments, including spine-related chronic disability and back pain, which stem from age-associated intervertebral disc degeneration (IDD). Given the rapid global rise in the aging population, understanding the biology of intervertebral disc aging in order to develop effective therapeutic interventions to combat the adverse effects of aging on disc health is now imperative. Fortunately, recent advances in aging research have begun to shed light on the basic biological process of aging. Here we review some of these insights and organize the complex process of disc aging into three different phases to guide research efforts to understand the biology of disc aging. The objective of this review is to provide an overview of the current knowledge and the recent progress made to elucidate specific molecular mechanisms underlying disc aging. In particular, studies over the last few years have uncovered cellular senescence and genomic instability as important drivers of disc aging. Supporting evidence comes from DNA repair-deficient animal models that show increased disc cellular senescence and accelerated disc aging. Additionally, stress-induced senescent cells have now been well documented to secrete catabolic factors, which can negatively impact the physiology of neighboring cells and ECM. These along with other molecular drivers of aging are reviewed in depth to shed crucial insights into the underlying mechanisms of age-related disc degeneration. We also highlight molecular targets for novel therapies and emerging candidate therapeutics that may mitigate age-associated IDD. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1289-1306, 2016.
authors.affiliation: Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.|Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Nam V
authors.initials: NV
authors.lastname: Vo
authors.affiliation: Department of Physical Medicine and Rehabilitation, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hartman
authors.affiliation: Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.|Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Prashanti R
authors.initials: PR
authors.lastname: Patil
authors.affiliation: Department of Orthopaedic Surgery and Graduate Program in Cell and Developmental Biology, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Makarand V
authors.initials: MV
authors.lastname: Risbud
authors.affiliation: Laboratory of Cell Proliferation and Ageing, Institute of Biosciences and Applications, National Centre for Scientific Research "Demokritos", Athens, Greece.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Kletsas
authors.affiliation: Leni & Peter W May Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York City, New York, 10029.
authors.forename: James C
authors.initials: JC
authors.lastname: Iatridis
authors.affiliation: Centre for Tissue Injury and Repair, Faculty of Medical and Human Sciences, University of Manchester M13 9PT and NIHR Manchester Musculoskeletal Biomedical Research Unit, Manchester Academic Health Science Centre, Manchester, United Kingdom.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Hoyland
authors.affiliation: Musculoskeletal and Regenerative Medicine Research Group, Biomolecular Sciences Research Centre, Sheffield Hallam University, Sheffield, S1 1WB, United Kingdom.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Le Maitre
authors.affiliation: Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.|Department of Physical Medicine and Rehabilitation, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Gwendolyn A
authors.initials: GA
authors.lastname: Sowa
authors.affiliation: Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: James D
authors.initials: JD
authors.lastname: Kang
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D006801:Humans; D007403:Intervertebral Disc / Q000378:metabolism* / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control
keywords: aging; cellular senescence; inflammation; intervertebral disc; oxidative damage