The Effect of a Bisphosphonate on the Life Span of Nothobranchius furzeri
Nitrogen containing bisphosphonates (e.g. alendronate) effectively inhibit osteoclastic bone resorption and are considered as first line treatment of osteoporosis and Paget´s disease. Additionally, several studies indicate a beneficial effect of nitrogen containing bisphosphonates on mortality, but the mechanisms of mortality reduction by nitrogen containing bisphosphonates are largely unexplored. Since there is only one randomized controlled trial with mortality as a secondary endpoint, this mortality reducing effect needs to be further investigated. Nothobranchius furzeri, an established model of accelerated aging, has an extremely short life cycle and is ideally suited as a model for this purpose.
Based on this, 100 16-weeks-old fish will be treated with alendronate and monitored for survival. In addition, 100 untreated control fish will be monitored. Bones from deceased fish (treated and untreated) will be examined by micro-computed tomography (μ-CT) analysis, histology and histomorphometry. In addition, immunohistochemistry for selected cytokines (TNF-alpha, IL-1, and IL-6), RNA sequencing and PCR analyses will be performed.
The primary objective of this study is to test the effect of alendronate treatment on the lifespan of Nothobranchius furzeri. We hypothesize that treatment will increase survival. As a secondary objective, the effects of alendronate treatment on bone remodeling, the immune system, and the cardiovascular system will be investigated. The proposed study will make a valuable contribution to define the effects of alendronate on mortality, bone remodeling, the cardiovascular and immune system in the turquoise killifish Nothobranchius furzeri.
Methods and Skills:
Micro-CT; bone histomorphometry; ELISA; research on turquoise killifish (Nothobranchius furzeri)
Föger-Samwald U, Kerschan-Schindl K, Butylina M, Pietschmann P. Age related osteoporosis: Targeting cellular senescence. Int J Mol Sci 23: 2701, 2022
Pietschmann P, Butylina M, Kerschan-Schindl K, Sipos W. Mechanisms of systemic osteoporosis in rheumatoid arthritis. Int J Mol Sci 23: 8740, 2022
Butylina M, Föger-Samwald U, Gamsjaeger S, Wahl-Figlash K, Kothmayer M, Paschalis EP, Pusch O, Pietschmann P. Nothobranchius furzeri, the Turquoise Killifish: A model of age-related osteoporosis?
Gerontology: 1-13, 2022 (Online ahead of print)
Wadiura LI, Butylina M, Reinprecht A, Aretin MB, Mischkulnig M, Gleiss A, Pietschmann P, Kerschan-Schindl K. Denosumab for prevention of acute onset immobilization-induced alterations of bone turnover: a randomized controlled trial. J Bone Miner Res, 2022 (Online ahead of print)