ZOLEDRONATE EXTENDS LIFESPAN AND HEALTHSPAN IN VIVO. (11th November 2018)

• Record Type: Journal Article
• Authors: Bellantuono, I; Chen, Z; Slack, C; Cordero, Julia; Zeidler, M
• Is Part Of: Innovation in aging. Volume 2(2018)Supplement 1
• Page Start: 545
• Page End: 545
• Publication Date: 2018-11-11
• Subjects: Aging -- Periodicals; Gerontology -- Periodicals; 612.67
• DOI: 10.1093/geroni/igy023.2012
• Languages: English
• ISSNs: 2399-5300

Abstract

Abstract: People are living longer but not healthier and develop multiple diseases in later life. New interventions, which prevents age-related diseases and improve healthspan are urgently required. Zoledronate is administered to prevent bone loss in patients affected by osteoporosis. Retrospective studies have shown that patients taking zoledronate have significantly increased survival compared to the placebo control group and improved resilience. The reasons for these effects are unknown but they seem too large to be exclusively the results of effective fractures' prevention. To understand whether the improved survival was the result of delayed ageing, firstly we have determined whether zoledronate was able to extend survival of human mesenchymal stem cells (hMSC) with age in vitro and have shown that this was the case. In addition hMSC maintained differentiation capacity to osteoblasts and adipogenic lineage, a property, which is usually lost with ageing in culture. This was associated with a reduced accumulation of DNA damage foci and was mediated by inhibition of mTOR signalling. In Drosophila Melanogaster, administration of zoledronate caused a significant extension in lifespan and improved signs of healthspan, i.e. improved ability to climb and prevention of intestinal epithelial dysplasia. Testing of healthspan in mice and clinical trial design in the context of frailty are ongoing according to the recommendations of the COST Action MouseAGE. MouseAGE is a European network of over 200 scientists from 25 EU countries and associated international partners, led by Bellantuono, which aims at reaching consensus on how to speed up translation of geroprotectors for patients' benefit.