title: Skeletal muscle as a regulator of the longevity protein, Klotho.
abstract: Klotho is a powerful longevity protein that has been linked to the prevention of muscle atrophy, osteopenia, and cardiovascular disease. Similar anti-aging effects have also been ascribed to exercise and physical activity. While an association between muscle function and Klotho expression has been previously suggested from longitudinal cohort studies, a direct relationship between circulating Klotho and skeletal muscle has not been investigated. In this paper, we present a review of the literature and preliminary evidence that, together, suggests Klotho expression may be modulated by skeletal muscle activity. Our pilot clinical findings performed in young and aged individuals suggest that circulating Klotho levels are upregulated in response to an acute exercise bout, but that the response may be dependent on fitness level. A similar upregulation of circulating Klotho is also observed in response to an acute exercise in young and old mice, suggesting that this may be a good model for mechanistically probing the role of physical activity on Klotho expression. Finally, we highlight overlapping signaling pathways that are modulated by both Klotho and skeletal muscle and propose potential mechanisms for cross-talk between the two. It is hoped that this review will stimulate further consideration of the relationship between skeletal muscle activity and Klotho expression, potentially leading to important insights into the well-documented systemic anti-aging effects of exercise.
authors.affiliation: Department of Physical Medicine and Rehabilitation, University of Pittsburgh Pittsburgh, PA, USA ; Division of Geriatric Medicine, Department of Medicine, University of Pittsburgh PA, USA.
authors.forename: Keith G
authors.initials: KG
authors.lastname: Avin
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh Pittsburgh, PA, USA ; Department of Health and Physical Education, University of Pittsburgh Pittsburgh, PA, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Coen
authors.affiliation: Department of Physical Medicine and Rehabilitation, University of Pittsburgh Pittsburgh, PA, USA.
authors.forename: Wan
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Cell Biology and Physiology, University of Pittsburgh Pittsburgh, PA, USA.
authors.forename: Donna B
authors.initials: DB
authors.lastname: Stolz
authors.affiliation: Department of Physical Medicine and Rehabilitation, University of Pittsburgh Pittsburgh, PA, USA.
authors.forename: Gwendolyn A
authors.initials: GA
authors.lastname: Sowa
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh Pittsburgh, PA, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Dubé
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh Pittsburgh, PA, USA.
authors.forename: Bret H
authors.initials: BH
authors.lastname: Goodpaster
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh Pittsburgh, PA, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: O'Doherty
authors.affiliation: Department of Physical Medicine and Rehabilitation, University of Pittsburgh Pittsburgh, PA, USA ; McGowan Institute for Regenerative Medicine, University of Pittsburgh Pittsburgh, PA, USA.
authors.forename: Fabrisia
authors.initials: F
authors.lastname: Ambrosio
keywords: Klotho; aging; exercise; regeneration; skeletal muscle