2019
DOI: 10.1371/journal.pcbi.1006639
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Abstract: Advancing age is the dominant risk factor for most of the major killer diseases in developed countries. Hence, ameliorating the effects of ageing may prevent multiple diseases simultaneously. Drugs licensed for human use against specific diseases have proved to be effective in extending lifespan and healthspan in animal models, suggesting that there is scope for drug repurposing in humans. New bioinformatic methods to identify and prioritise potential anti-ageing compounds for humans are therefore of interest.… Show more

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Cited by 32 publications
(25 citation statements)
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References 61 publications
(87 reference statements)
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“…Mutations in Alk that result in its mis‐expression and/or constitutive activation have been described in a number of human cancer types, leading to the development of clinically approved small molecule Alk inhibitors (Hallberg & Palmer, 2013). In aging research, one promising direction to translation of basic research findings is the repurposing of existing drugs for use as interventions against aspects of the aging process itself (Dönertaş, Valenzuela, Partridge, & Thornton, 2018; Fuentealba et al, 2019; Ziehm et al, 2017). We therefore chose to test three small molecule Alk inhibitors for their effect on longevity: two drugs (alectinib and crizotinib) that have been clinically approved for treatment of Alk‐positive non‐small‐cell lung cancer (Kwak et al, 2010; Peters et al, 2017), and one molecule (TAE‐684) that is not yet clinically approved but has been previously used in studies of Alk function in mammalian and Drosophila disease models (Galkin et al, 2007; Gouzi et al, 2011, 2018).…”
Section: Resultsmentioning
confidence: 99%
“…Mutations in Alk that result in its mis‐expression and/or constitutive activation have been described in a number of human cancer types, leading to the development of clinically approved small molecule Alk inhibitors (Hallberg & Palmer, 2013). In aging research, one promising direction to translation of basic research findings is the repurposing of existing drugs for use as interventions against aspects of the aging process itself (Dönertaş, Valenzuela, Partridge, & Thornton, 2018; Fuentealba et al, 2019; Ziehm et al, 2017). We therefore chose to test three small molecule Alk inhibitors for their effect on longevity: two drugs (alectinib and crizotinib) that have been clinically approved for treatment of Alk‐positive non‐small‐cell lung cancer (Kwak et al, 2010; Peters et al, 2017), and one molecule (TAE‐684) that is not yet clinically approved but has been previously used in studies of Alk function in mammalian and Drosophila disease models (Galkin et al, 2007; Gouzi et al, 2011, 2018).…”
Section: Resultsmentioning
confidence: 99%
“…In addition to existing drugs whose promising anti‐aging potential should be safely tested in humans (Partridge et al, 2020), designing novel therapies capable of improving human health span will require well‐considered molecular targets. A wide variety of approaches have been historically utilized to identify aging‐relevant targets and therapeutics, including RNAi screening in worms (Hansen et al, 2005), computational screening of the protein–drug interactome (Fuentealba et al, 2019), and omics‐level expression screening in mice (Villeda et al, 2011). As an example of the latter, young mice exposed to the blood of old mice via heterochronic parabiosis exhibit decreased synaptic plasticity as well as impairments in memory and learning.…”
Section: Introductionmentioning
confidence: 99%
“…A comprehensive list with these longevity-associated genes (LAGs), including more detailed information about lifespan experiments, can be found in the GenAge database 4 . This type and amount of data have made it possible for higher level analyses to be performed [5][6][7] , and the collection of LAGs in public repositories has significantly pushed biogerontology towards more integrative approaches to study longevity. One important aspect observed is that many LAGs seem to act in a cooperative manner [8][9][10] and are not independent regulators of lifespan.…”
Section: Background and Summarymentioning
confidence: 99%