Life extension in
            <i>Drosophila</i>
            by feeding a drug

Kang, Hyung-Lyun; Benzer, Seymour; Min, Kyung‐Tai

doi:10.1073/pnas.022631999

Cited by 283 publications

(188 citation statements)

References 38 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%

“…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

113

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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: Introductionmentioning

confidence: 99%

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

113

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“…Previous studies have reported elevated antioxidant enzyme activity from treatment with butyrate and HDAC inhibitors (Kang et al ., 2002; Shimazu et al ., 2013). Consistent with this, we found that butyrate prevented oxidative damage to proteins during aging and increased catalase activity in muscle.…”

Section: Discussionmentioning

confidence: 99%

The histone deacetylase inhibitor butyrate improves metabolism and reduces muscle atrophy during aging

Walsh¹,

et al. 2015

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SummarySarcopenia, the loss of skeletal muscle mass and function during aging, is a major contributor to disability and frailty in the elderly. Previous studies found a protective effect of reduced histone deacetylase activity in models of neurogenic muscle atrophy. Because loss of muscle mass during aging is associated with loss of motor neuron innervation, we investigated the potential for the histone deacetylase (HDAC) inhibitor butyrate to modulate age‐related muscle loss. Consistent with previous studies, we found significant loss of hindlimb muscle mass in 26‐month‐old C57Bl/6 female mice fed a control diet. Butyrate treatment starting at 16 months of age wholly or partially protected against muscle atrophy in hindlimb muscles. Butyrate increased muscle fiber cross‐sectional area and prevented intramuscular fat accumulation in the old mice. In addition to the protective effect on muscle mass, butyrate reduced fat mass and improved glucose metabolism in 26‐month‐old mice as determined by a glucose tolerance test. Furthermore, butyrate increased markers of mitochondrial biogenesis in skeletal muscle and whole‐body oxygen consumption without affecting activity. The increase in mass in butyrate‐treated mice was not due to reduced ubiquitin‐mediated proteasomal degradation. However, butyrate reduced markers of oxidative stress and apoptosis and altered antioxidant enzyme activity. Our data is the first to show a beneficial effect of butyrate on muscle mass during aging and suggests HDACs contribute to age‐related muscle atrophy and may be effective targets for intervention in sarcopenia and age‐related metabolic disease.

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“…These include screening genetic mutants for longevity phenotypes (Lin et al 1998), overexpression of genes known to enhance antioxidant defense mechanisms (Parkes et al 1998), generational selection studies (Rose et al 1992), and environmental strategies such as drug consumption (e.g., 4-phenylbutyrate; PBA; Kang et al 2002) or caloric restriction (Clancy et al 2002;Mair et al 2003). It is becoming increasingly clear that different genetic and environmental strategies for life extension lead to different patterns of gerontological decline in functional abilities of Drosophila (e.g., flight, locomotion, visuo-motor coordination, memory, and learning).…”

Section: Discussionmentioning

confidence: 99%

Improved functional abilities of the life-extended Drosophila mutant Methuselah are reversed at old age to below control levels

Petrosyan

Gonçalves

Hsieh

et al. 2013

AGE

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Methuselah (mth) is a chromosome 3 Drosophila mutant with an increased lifespan. A large number of studies have investigated the genetic, molecular, and biochemical mechanisms of the mth gene. Much less is known about the effects of mth on preservation of sensorimotor abilities throughout Drosophila's lifespan, particularly in late life. The current study investigated functional senescence in mth and its parental-control line (w1118) in two experiments that measured age-dependent changes in flight functions and locomotor activity. In experiment 1, a total of 158 flies (81 mth and 77 controls) with an age range from 10 to 70 days were individually tethered under an infrared laser-sensor system that allowed monitoring of flight duration during phototaxic flight. We found that mth has a statistically significant advantage in maintaining continuous flight over control flies at age 10 days, but not during middle and late life. At age 70 days, the trend reversed and parental control flies had a small but significant advantage, suggesting an interaction between age and genotype in the ability to sustain flight. In experiment 2, a total of 173 different flies (97 mth and 76 controls) with an age range from 50 to 76 days were individually placed in a large well-lit arena (60×45 cm) and their locomotor activity quantified as the distance walked in a 1-min period. Results showed that mth flies had lower levels of locomotor activity relative to controls at ages 50 and 60 days. These levels converged for the two genotypes at the oldest ages tested. Findings show markedly different patterns of functional decline for the mth line relative to those previously reported for other life-extended genotypes, suggesting that different life-extending genes have dissimilar effects on preservation of sensory and motor abilities throughout an organism's lifespan.

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Life extension in Drosophila by feeding a drug

Cited by 283 publications

References 38 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

The histone deacetylase inhibitor butyrate improves metabolism and reduces muscle atrophy during aging

Improved functional abilities of the life-extended Drosophila mutant Methuselah are reversed at old age to below control levels

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