Rapid iterative negative geotaxis (RING): a new method for assessing age-related locomotor decline in

Gargano, Julia W.; Martin, Ian; Bhandari, Poonam; Grotewiel, Mike

doi:10.1016/j.exger.2005.02.005

Cited by 442 publications

(460 citation statements)

References 43 publications

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“…The studies reported here, in conjunction with previous work from our group (Goddeeris et al 2003;Gargano et al 2005) and others (Miquel et al 1976;Arking and Wells 1990;Chavous et al 2001;Mockett et al 2001;Kang et al 2002;Ruan et al 2002;Morrow et al 2004;Simon et al 2006), indicate that locomotor senescence might be mechanistically connected to life span in Drosophila; i.e. long-lived flies tend to have better locomotor function across age.…”

Section: Discussionsupporting

confidence: 77%

“…Previous studies (Gibert et al 2001;Gargano et al 2005;Martinez et al 2007) have not resolved, however, whether the vertical distance moved in negative geotaxis assays reflects climbing, jumping, flying, or some combination of these behaviors. Additionally, it was unclear from published reports whether the age-related impairment in negative geotaxis is due to decreased speed of vertical movement, increased latency to initiate vertical movement, or some combination of these two age-related changes.…”

Section: Resultsmentioning

confidence: 96%

“…Negative geotaxis (startleinduced vertical movement) is a frequently used index of locomotor behavior in flies (Miquel et al 1976;Arking and Wells 1990;Chavous et al 2001;Mockett et al 2001;Kang et al 2002;Ruan et al 2002;Goddeeris et al 2003;Morrow et al 2004;Gargano et al 2005;Simon et al 2006).Despite being commonly assessed, it was previously unclear whether negative geotaxis is principally a climbing behavior or a combination of climbing and other behaviors such as jumping and flying. Additionally, it was previously unclear whether age-related impairment in negative geotaxis is due to a decreased speed of vertical movement, an increased latency to initiate vertical movement, or other age-related behavioral changes.…”

Section: Introductionmentioning

confidence: 99%

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Genetic and environmental factors impact age-related impairment of negative geotaxis in Drosophila by altering age-dependent climbing speed

Rhodenizer

Martin

Bhandari

et al. 2008

Experimental Gerontology

117

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Age-related locomotor impairment in humans is important clinically because it is associated with several co-morbidities and increased risk of death. One of the hallmarks of age-related locomotor impairment in humans is a decrease in walking speed with age. Genetically tractable model organisms such as Drosophila are essential for delineating mechanisms underlying age-related locomotor impairment and age-related decreases in locomotor speed. Negative geotaxis, the ability of flies to move vertically when startled, is a common measure of locomotor behavior that declines with age in Drosophila. Toward further developing Drosophila as a model for age-related locomotor impairment, we investigated whether negative geotaxis reflects climbing or a combination of climbing and other behaviors such as flying and jumping. Additionally, we investigated whether locomotor speed in negative geotaxis assays declines with age in flies as found for walking speed in humans. We find that the vast majority of flies climb during negative geotaxis assays and that removal of hind legs, but not wings, impairs the behavior. We also find that climbing speed decreases with age in four wild type genetic backgrounds, in flies housed at different temperatures, and in control and long-lived flies harboring a mutation in OR83b. The decreases in climbing speed correlate with the age-related impairments in the distance climbed. These studies establish negative geotaxis in Drosophila as a climbing behavior that declines with age due to a decrease in climbing speed. Agerelated decreases in locomotor speed are common attributes of locomotor senescence in flies and humans.

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Section: Discussionsupporting

confidence: 77%

Section: Resultsmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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Genetic and environmental factors impact age-related impairment of negative geotaxis in Drosophila by altering age-dependent climbing speed

Rhodenizer

Martin

Bhandari

et al. 2008

Experimental Gerontology

117

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“…Negative geotaxis was assessed in Rapid Negative Geotaxis (RING) assays in groups of 100 flies as described (27). Flies were tested 5 times per week for 5 weeks to assess the decline in negative geotaxis speed with age.…”

Section: Methodsmentioning

confidence: 99%

A Novel MitoTimer Reporter Gene for Mitochondrial Content, Structure, Stress, and Damage in Vivo

Laker

Ryall

et al. 2014

Journal of Biological Chemistry

214

247

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Background: Mitochondrial health is difficult to assess in vivo. Results: We have generated a reporter gene, MitoTimer, which targets mitochondria, and fluoresces green and shifts to red when oxidized, for assessment of mitochondrial content, structure, stress, and damage under physiological and pathological conditions. Conclusion: MitoTimer is useful for assessment of mitochondrial health in vivo. Significance: MitoTimer could advance mitochondrial research in multiple disciplines.

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“…An important feature of Indy life span extension is that it dramatically extends life span with very few physiological tradeoffs. For example, Indy flies show no reduction in resting metabolic rate and early or late life fecundity under normal laboratory rearing conditions, and no decrease in maximal flight velocity, negative geotaxis or 24-hour activity levels has been detected (12)(13)(14). It has been proposed that a decrease in Indy expression might extend life span by affecting intermediary metabolism and creating a metabolic state that overlaps with or mimics CR.…”

mentioning

confidence: 99%

Long-lived Indy and calorie restriction interact to extend life span

Wang

Neretti²,

Whitaker³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

101

160

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Calorie restriction (CR) improves health and extends life span in a variety of species. Despite many downstream molecules and physiological systems having been identified as being regulated by CR, the mechanism by which CR extends life span remains unclear. The Drosophila gene Indy (for I'm not dead yet), involved in the transport and storage of Krebs cycle intermediates in tissues important in fly metabolism, was proposed to regulate life span via an effect on metabolism that could overlap with CR. In this study, we report that CR down regulates Indy mRNA expression, and that CR and the level of Indy expression interact to affect longevity. Optimal life span extension is seen when Indy expression is decreased between 25 and 75% of normal. Indy long-lived flies show several phenotypes that are shared by long-lived CR flies, including decreased insulin-like signaling, lipid storage, weight gain, and resistance to starvation as well as an increase in spontaneous physical activity. We conclude that Indy and CR interact to affect longevity and that a decrease in Indy may induce a CR-like status that confers life span extension.Drosophila ͉ insulin ͉ physical activity ͉ triglyceride A ging is a complex biological process that causes deteriorative changes over time. It has been suggested that the interplay between environmental factors and genetic alterations may affect this near universal process. Calorie restriction (CR) is the most widely recognized life span-extending intervention, and it has been shown to extend lifespan in a variety of different organisms (1, 2). Progress has been made in identifying genes that regulate longevity, and many of them appear to belong to pathways related to nutrient sensing, metabolism or nutrient/ metabolic signaling (3-7). The life span extending effects of a subset of these longevity genes has been shown to be associated with, and in some cases, causally related to CR life span extension (chico, Sir2, p53). Studies have suggested that alterations in the activity of these genes may mediate elements of the normal CR life span extending effect. Despite these advances little is understood about the molecular and genetic mechanisms underlying the healthy life span extension of CR.In Drosophila melanogaster, mutations in the Indy gene dramatically extend life span (8). The INDY protein is a transmembrane transporter of Krebs cycle intermediates (citrate, succinate, fumarate, and alpha-ketoglutarate) predominantly found at the plasma membrane of cells in the midgut, fat body, and oenocytes, tissues important for the uptake, utilization, and storage of nutrients and the principal sites of intermediary metabolism in the fly (8-10). Several independently derived lines, each with a P-element in the non-coding region of the Indy locus leading to decreased expression of Indy mRNA, have been shown to extend life span. It has been reported that life span extension is seen even when the Indy mutation is crossed into different genetic backgrounds (e.g., Hyperkinetic, Shaker, drop dead, and the lo...

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Rapid iterative negative geotaxis (RING): a new method for assessing age-related locomotor decline in

Cited by 442 publications

References 43 publications

Genetic and environmental factors impact age-related impairment of negative geotaxis in Drosophila by altering age-dependent climbing speed

Genetic and environmental factors impact age-related impairment of negative geotaxis in Drosophila by altering age-dependent climbing speed

A Novel MitoTimer Reporter Gene for Mitochondrial Content, Structure, Stress, and Damage in Vivo

Long-lived Indy and calorie restriction interact to extend life span

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