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• 21. [Article] Influences of an Anti-inflammatory Drug, Ibuprofen, on Spatial Memory and NMDA Receptor Subunit Expression During Aging

  One of the first cognitive dysfunctions to arise with aging is memory loss, affecting an estimated 85% of elderly in the U.S. over the age of 80 with Age Associated Memory Impairment. A common feature ...

  Citation × Citation Citation Abstract Copy Title: Influences of an Anti-inflammatory Drug, Ibuprofen, on Spatial Memory and NMDA Receptor Subunit Expression During Aging Author: Marquez Loza, Alejandra One of the first cognitive dysfunctions to arise with aging is memory loss, affecting an estimated 85% of elderly in the U.S. over the age of 80 with Age Associated Memory Impairment. A common feature in humans and animals experiencing memory loss with aging is the decline in N-methyl-D-aspartate (NMDA) receptorbinding densities in the brain. Variability in the effects of aging on the GluN1 subunit suggests that inflammation may play a role in NMDA receptor aging. The purpose of the present study was to determine the effects of an anti-inflammatory drug, ibuprofen, on spatial long-term & short-term memory and cognitive flexibility in male C57BL/6 mice from four different age groups (5, 14, 20, and 26 months of age at the end of testing). Mice were fed either Ibuprofen (375 ppm) in NIH31 diet or NIH31 diet alone for 6 weeks prior to testing. This dose had been shown to reduce pathology in an Alzheimer’s disease mouse model. Behavioral testing using the Morris Water Maze showed a significant effect of age on acquisition of spatial reference memory, the formation of spatial memory bias in probe trials, cognitive flexibility in reversal trials, and working memory, with 20 and 26 month old mice performing significantly worse than 5 month old mice. Ibuprofen enhanced overall performance in the working memory task when data was collapsed across naïve and test trials and ages. The oldest mice receiving ibuprofen showed significantly better delayed working memory, but near significantly (p=0.08) worse spatial reference memory, as compared to age-matched controls. In situ hybridization assays showed significant decreases over all ages in the mRNA densities for the GluN2B subunit, all GluN1 splice variants, and the GluN1-1 splice forms in the frontal lobes of mice consuming ibuprofen. The GluN1-3 splice form mRNA was significantly increased across ages in the frontal lobes of the ibuprofen-treated mice. There was no effect of ibuprofen on IL-1beta expression in the brains or spleens of these mice. These findings suggest that inflammation may play a role in working memory declines in aged animals, but the reducing effects of ibuprofen across ages on several factors, without reducing age-related increases in cytokine expression suggests that ibuprofen has effects on mRNA for the NMDA receptor that are unrelated to aging or inflammation. Title: Influences of an Anti-inflammatory Drug, Ibuprofen, on Spatial Memory and NMDA Receptor Subunit Expression During Aging Author: Marquez Loza, Alejandra One of the first cognitive dysfunctions to arise with aging is memory loss, affecting an estimated 85% of elderly in the U.S. over the age of 80 with Age Associated Memory Impairment. A common feature in humans and animals experiencing memory loss with aging is the decline in N-methyl-D-aspartate (NMDA) receptorbinding densities in the brain. Variability in the effects of aging on the GluN1 subunit suggests that inflammation may play a role in NMDA receptor aging. The purpose of the present study was to determine the effects of an anti-inflammatory drug, ibuprofen, on spatial long-term & short-term memory and cognitive flexibility in male C57BL/6 mice from four different age groups (5, 14, 20, and 26 months of age at the end of testing). Mice were fed either Ibuprofen (375 ppm) in NIH31 diet or NIH31 diet alone for 6 weeks prior to testing. This dose had been shown to reduce pathology in an Alzheimer’s disease mouse model. Behavioral testing using the Morris Water Maze showed a significant effect of age on acquisition of spatial reference memory, the formation of spatial memory bias in probe trials, cognitive flexibility in reversal trials, and working memory, with 20 and 26 month old mice performing significantly worse than 5 month old mice. Ibuprofen enhanced overall performance in the working memory task when data was collapsed across naïve and test trials and ages. The oldest mice receiving ibuprofen showed significantly better delayed working memory, but near significantly (p=0.08) worse spatial reference memory, as compared to age-matched controls. In situ hybridization assays showed significant decreases over all ages in the mRNA densities for the GluN2B subunit, all GluN1 splice variants, and the GluN1-1 splice forms in the frontal lobes of mice consuming ibuprofen. The GluN1-3 splice form mRNA was significantly increased across ages in the frontal lobes of the ibuprofen-treated mice. There was no effect of ibuprofen on IL-1beta expression in the brains or spleens of these mice. These findings suggest that inflammation may play a role in working memory declines in aged animals, but the reducing effects of ibuprofen across ages on several factors, without reducing age-related increases in cytokine expression suggests that ibuprofen has effects on mRNA for the NMDA receptor that are unrelated to aging or inflammation. Close

• 22. [Article] Employee Age Differences in Formal Performance Feedback Reactions: Examining the Effects of Perceived Valence, Content, and Delivery

  As the nature of work is rapidly changing, organizations in developed nations all over the world are experiencing shifts in the age composition of their workforces. These changes, which include an aging ...

  Citation × Citation Citation Abstract Copy Title: Employee Age Differences in Formal Performance Feedback Reactions: Examining the Effects of Perceived Valence, Content, and Delivery Author: Burlacu, Gabriela Year: 2011 As the nature of work is rapidly changing, organizations in developed nations all over the world are experiencing shifts in the age composition of their workforces. These changes, which include an aging workforce that is becoming increasingly age-diverse, indicate that organizational researchers and practitioners need to be better aware of how age differences manifest themselves in the workplace and what implications this has for effective employee management. In the current study it is proposed that employees of different ages react differently to various elements of a formal performance feedback event. Specifically, Carstensen's developmental Socio-emotional Selectivity Theory is used as a theoretical backing for explaining how and why employees of different ages perceive and react to performance feedback differently based on their perceptions of the valence, content quality, and delivery quality of the feedback. The results show evidence of age differences in feedback reactions, with younger adults being particularly concerned with information that will benefit them in the future and older adults being particularly concerned with information that conveys a positive relationship with one's supervisor. These findings have both conceptual and practical implications as we seek to build workplace aging theory and find ways to better manage and retain valuable employees of all ages in a changing world of work. Title: Employee Age Differences in Formal Performance Feedback Reactions: Examining the Effects of Perceived Valence, Content, and Delivery Author: Burlacu, Gabriela Year: 2011 As the nature of work is rapidly changing, organizations in developed nations all over the world are experiencing shifts in the age composition of their workforces. These changes, which include an aging workforce that is becoming increasingly age-diverse, indicate that organizational researchers and practitioners need to be better aware of how age differences manifest themselves in the workplace and what implications this has for effective employee management. In the current study it is proposed that employees of different ages react differently to various elements of a formal performance feedback event. Specifically, Carstensen's developmental Socio-emotional Selectivity Theory is used as a theoretical backing for explaining how and why employees of different ages perceive and react to performance feedback differently based on their perceptions of the valence, content quality, and delivery quality of the feedback. The results show evidence of age differences in feedback reactions, with younger adults being particularly concerned with information that will benefit them in the future and older adults being particularly concerned with information that conveys a positive relationship with one's supervisor. These findings have both conceptual and practical implications as we seek to build workplace aging theory and find ways to better manage and retain valuable employees of all ages in a changing world of work. Close

• 23. [Article] Age at disability onset and self-reported health status

  This is the publisher’s final pdf. The published article is copyrighted by BioMed Central Ltd. and can be found at: http://www.biomedcentral.com/bmcpublichealth/.

  Citation × Citation Citation Abstract Copy Title: Age at disability onset and self-reported health status Author: Drum, Charles, Beatty, Phillip, Nosek, Margaret A., Hall, Trevor, Campbell, Vincent A., Jamoom, Eric W., Andresen, Elena M., Suzuki, Rie, Krahn, Gloria, Fujiura, Glenn, Horner-Johnson, Willi, Cardinal, Brad This is the publisher’s final pdf. The published article is copyrighted by BioMed Central Ltd. and can be found at: http://www.biomedcentral.com/bmcpublichealth/. Title: Age at disability onset and self-reported health status Author: Drum, Charles, Beatty, Phillip, Nosek, Margaret A., Hall, Trevor, Campbell, Vincent A., Jamoom, Eric W., Andresen, Elena M., Suzuki, Rie, Krahn, Gloria, Fujiura, Glenn, Horner-Johnson, Willi, Cardinal, Brad This is the publisher’s final pdf. The published article is copyrighted by BioMed Central Ltd. and can be found at: http://www.biomedcentral.com/bmcpublichealth/. Close

• 24. [Article] Persistence and age-age genetic correlations of stem defects in Douglas-fir (Pseudotsuga menziesii var. menziesii (Mirb.) Franco)

  Stem defects, including sinuosity, large branches, and the occurrence of steep-angled branches (e.g., forks and ramicorns) can occur with high frequency in young plantations of Coastal Douglas-fir (Pseudotsuga ...

  Citation × Citation Citation Abstract Copy Title: Persistence and age-age genetic correlations of stem defects in Douglas-fir (Pseudotsuga menziesii var. menziesii (Mirb.) Franco) Author: Temel, Fatih Stem defects, including sinuosity, large branches, and the occurrence of steep-angled branches (e.g., forks and ramicorns) can occur with high frequency in young plantations of Coastal Douglas-fir (Pseudotsuga menziesii var. menziesii (Mirb.) Franco). The importance of including these stem defects as criteria in early selection depends, in great part, on their persistence over time, and the efficiency of early selection for these traits. In this study, 90 open-pollinated families of Douglas-fir growing on three test sites in the Oregon Coast Range, and originally measured in 1984 at age 12, were remeasured in 1996, at age 24 (approximate mid-rotation age for managed plantations in this region). While the majority (62%) of trees scored as having ramicoms at age 12 still had them at age 24, most forks (53%) had become ramicorns by the second measurement. Thus, there does not seem to be a need to score forks and ramicorns separately. Although branch size was highly correlated between the two measurement dates, sinuosity scores were poorly correlated. Estimated heritabilities and genetic correlations between stem defect traits, and between stem defect traits and bole diameter at breast height (DBH), were similar at the two ages. Due to low heritabilities, estimated genetic gains for DBH and individual stem defect traits were low but consistent with earlier studies. Both branch size and the number of whorls with steep-angled branches had positive genetic correlations with DBH, indicating that selection for stem size alone will indirectly increase stem defects. Thus, it may be prudent to include these traits along with DBH as selection criteria. Sinuosity was nearly uncorrelated with DBH. With the exception of sinuosity, genetic correlations between comparable traits at the two ages were very high (>0.75), and predicted correlated responses in these traits at age 24, from selection at age 12, were nearly as great as those expected if selection was delayed until age 24. Title: Persistence and age-age genetic correlations of stem defects in Douglas-fir (Pseudotsuga menziesii var. menziesii (Mirb.) Franco) Author: Temel, Fatih Stem defects, including sinuosity, large branches, and the occurrence of steep-angled branches (e.g., forks and ramicorns) can occur with high frequency in young plantations of Coastal Douglas-fir (Pseudotsuga menziesii var. menziesii (Mirb.) Franco). The importance of including these stem defects as criteria in early selection depends, in great part, on their persistence over time, and the efficiency of early selection for these traits. In this study, 90 open-pollinated families of Douglas-fir growing on three test sites in the Oregon Coast Range, and originally measured in 1984 at age 12, were remeasured in 1996, at age 24 (approximate mid-rotation age for managed plantations in this region). While the majority (62%) of trees scored as having ramicoms at age 12 still had them at age 24, most forks (53%) had become ramicorns by the second measurement. Thus, there does not seem to be a need to score forks and ramicorns separately. Although branch size was highly correlated between the two measurement dates, sinuosity scores were poorly correlated. Estimated heritabilities and genetic correlations between stem defect traits, and between stem defect traits and bole diameter at breast height (DBH), were similar at the two ages. Due to low heritabilities, estimated genetic gains for DBH and individual stem defect traits were low but consistent with earlier studies. Both branch size and the number of whorls with steep-angled branches had positive genetic correlations with DBH, indicating that selection for stem size alone will indirectly increase stem defects. Thus, it may be prudent to include these traits along with DBH as selection criteria. Sinuosity was nearly uncorrelated with DBH. With the exception of sinuosity, genetic correlations between comparable traits at the two ages were very high (>0.75), and predicted correlated responses in these traits at age 24, from selection at age 12, were nearly as great as those expected if selection was delayed until age 24. Close

• 25. [Article] Age determination of corvina reina (Cynoscion albus) in the Gulf of Nicoya, based on otolith surface readings and microincrement analysis

  The corvina reina (Cynoscion albus) is an important part of the artisanal fishery in the Gulf of Nicoya, Costa Rica. Stock assessment on this sciaenid species has been restricted to the use of length-based ...

  Citation × Citation Citation Abstract Copy Title: Age determination of corvina reina (Cynoscion albus) in the Gulf of Nicoya, based on otolith surface readings and microincrement analysis Author: Mug-Villanueva, Moises The corvina reina (Cynoscion albus) is an important part of the artisanal fishery in the Gulf of Nicoya, Costa Rica. Stock assessment on this sciaenid species has been restricted to the use of length-based methods because of the lack of age data. Direct age determination methodologies for tropical species often encounter serious difficulties such as poorly defined hyaline and opaque zones and lack of adequate techniques of ageing. This thesis presents the results of an age-determination study of Cynoscion albus based on otolith surface readings and microincrement analysis. Age estimates were obtained from counts of hyaline zones from surface readings using the light microscope and from microincrement readings from cross sections of the otolith using the scanning electron microscope. Validation of age estimates from surface readings was based on a linear regression of the age estimates from surface readings on age estimates from integrated daily increment readings. Growth of the otolith was studied using linear and multivariate regression methods and the results were used to construct multivariate models for prediction of age. Consistent estimates of age and fish growth parameters were obtained from surface and microincrement analysis. This study showed that Cynoscion albus is a slow-growing fish (K = 0.121) and reaches a large size (L∞ = 127.5 cm) and therefore is likely to suffer overfishing in the Gulf of Nicoya fishery. Title: Age determination of corvina reina (Cynoscion albus) in the Gulf of Nicoya, based on otolith surface readings and microincrement analysis Author: Mug-Villanueva, Moises The corvina reina (Cynoscion albus) is an important part of the artisanal fishery in the Gulf of Nicoya, Costa Rica. Stock assessment on this sciaenid species has been restricted to the use of length-based methods because of the lack of age data. Direct age determination methodologies for tropical species often encounter serious difficulties such as poorly defined hyaline and opaque zones and lack of adequate techniques of ageing. This thesis presents the results of an age-determination study of Cynoscion albus based on otolith surface readings and microincrement analysis. Age estimates were obtained from counts of hyaline zones from surface readings using the light microscope and from microincrement readings from cross sections of the otolith using the scanning electron microscope. Validation of age estimates from surface readings was based on a linear regression of the age estimates from surface readings on age estimates from integrated daily increment readings. Growth of the otolith was studied using linear and multivariate regression methods and the results were used to construct multivariate models for prediction of age. Consistent estimates of age and fish growth parameters were obtained from surface and microincrement analysis. This study showed that Cynoscion albus is a slow-growing fish (K = 0.121) and reaches a large size (L∞ = 127.5 cm) and therefore is likely to suffer overfishing in the Gulf of Nicoya fishery. Close

• 26. [Article] The effects of different otolith ageing techniques on estimates of growth and mortality for two species of rockfishes, Sebastes pinniger and Sebastes diploproa

  The use of some age determination methods may result in the incorrect age structure of fish populations. This in turn may lead to incorporation of inappropriate data into models used for stock management. ...

  Citation × Citation Citation Abstract Copy Title: The effects of different otolith ageing techniques on estimates of growth and mortality for two species of rockfishes, Sebastes pinniger and Sebastes diploproa Author: Wilson, Christopher D. The use of some age determination methods may result in the incorrect age structure of fish populations. This in turn may lead to incorporation of inappropriate data into models used for stock management. Otoliths are commonly used for determining the age of fishes, and ages based on the whole otoliths (surface ages) are often lower than those based on otolith sections of long-lived, slow-growing fishes such as rockfishes (Sebastes spp.). Therefore, significant overestimates in growth and mortality may occur when surface ages are used for these species. This study provides estimates of growth and total instantaneous mortality for Sebastes diploproa and S. pinniger based on ages determined from the otolith surface versus those determined from otolith sections. For both species, estimates of mortality were reduced by more than half when section rather than surface ages were used. Estimates of growth based on surface rather than section ages were nearly identical for S. diploproa but appeared higher for S. pinniger. The inclusion of posterior otolith projections in the surface counts of S. diploproa and not S. pinniger are suspected of producing these differences. Because of these revised estimates of mortality and growth the life history features and response to exploitation of these species must be re-evaluated. Maximum sustainable yields of S. ninniger and S. diploproa based on surface ages are 2 to 5 times greater for either species than yields based on section ages. Mistaken estimates such as these can lead to management errors resulting in overexploitation and may thus explain the depletion of some stocks of Sebastes spp.. Title: The effects of different otolith ageing techniques on estimates of growth and mortality for two species of rockfishes, Sebastes pinniger and Sebastes diploproa Author: Wilson, Christopher D. The use of some age determination methods may result in the incorrect age structure of fish populations. This in turn may lead to incorporation of inappropriate data into models used for stock management. Otoliths are commonly used for determining the age of fishes, and ages based on the whole otoliths (surface ages) are often lower than those based on otolith sections of long-lived, slow-growing fishes such as rockfishes (Sebastes spp.). Therefore, significant overestimates in growth and mortality may occur when surface ages are used for these species. This study provides estimates of growth and total instantaneous mortality for Sebastes diploproa and S. pinniger based on ages determined from the otolith surface versus those determined from otolith sections. For both species, estimates of mortality were reduced by more than half when section rather than surface ages were used. Estimates of growth based on surface rather than section ages were nearly identical for S. diploproa but appeared higher for S. pinniger. The inclusion of posterior otolith projections in the surface counts of S. diploproa and not S. pinniger are suspected of producing these differences. Because of these revised estimates of mortality and growth the life history features and response to exploitation of these species must be re-evaluated. Maximum sustainable yields of S. ninniger and S. diploproa based on surface ages are 2 to 5 times greater for either species than yields based on section ages. Mistaken estimates such as these can lead to management errors resulting in overexploitation and may thus explain the depletion of some stocks of Sebastes spp.. Close

• 27. [Article] Length and age at maturity of female yelloweye rockfish (Sebastes rubberimus) and cabezon (Scorpaenichthys marmoratus) from Oregon waters based on histological evaluation of maturity Information Report number 2009-04

  Abstract -- Accurate estimates of female age or length at maturity are critical for the conservation of exploited fish stocks. Age at maturity is particularly important, as it strongly influences population ...

  Citation × Citation Citation Abstract Copy Title: Length and age at maturity of female yelloweye rockfish (Sebastes rubberimus) and cabezon (Scorpaenichthys marmoratus) from Oregon waters based on histological evaluation of maturity Information Report number 2009-04 Abstract -- Accurate estimates of female age or length at maturity are critical for the conservation of exploited fish stocks. Age at maturity is particularly important, as it strongly influences population model estimates of sustainable harvest rates (Clark 1991) and, along with mean body size, is an important predictor of the risk of overexploitation (Reynolds et al. 2005). For many U.S. west coast groundfish stocks, data on age and length at maturity is of poor quality. The age at maturity curves used in many stock assessments are currently based on macroscopic (visual) assessment of ovary condition. However, there is abundant evidence that histological evaluation of ovarian thin-sections, especially if combined with optimal seasonal sampling, is much more accurate (Gunderson et al. 1980, Wyllie Echeverria 1987, West 1990, Nichol and Pikitch 1994, Hannah and Parker 2007). The age data that have been used to develop curves of age at maturity for some species is also based on outdated ageing methods, such as surface aging of otoliths, as opposed to the more accurate “break and burn” technique (Barss 1989, Wyllie Echeverria 1987, Chilton and Beamish 1982). For other species, such as cabezon (Scorpaenichthys marmoratus), accurate age and growth data, based on thin-sectioning of otoliths, have just recently been developed (Grebel and Cailliet 2003). Information on age and length at maturity that is based on histological evaluation of maturity status and modern ageing techniques is therefore needed for many U.S. west coast groundfish species. Histology-based maturity data has been developed for some U.S. west coast groundfish species. These include darkblotched rockfish (Sebastes crameri, Nichol and Pikitch 1994), petrale sole (Eopsetta jordani, Hannah et al. 2002), greenstriped rockfish (Sebastes elongatus, Shaw and Gunderson 2006), Pacific ocean perch (Sebastes alutus, Hannah and Parker 2007) and rosethorn rockfish (Sebastes helvomaculatus, Shaw and Gunderson 2008). We report here on the development of similar data for female yelloweye rockfish (Sebastes rubberimus) and cabezon. Title: Length and age at maturity of female yelloweye rockfish (Sebastes rubberimus) and cabezon (Scorpaenichthys marmoratus) from Oregon waters based on histological evaluation of maturity Information Report number 2009-04 Abstract -- Accurate estimates of female age or length at maturity are critical for the conservation of exploited fish stocks. Age at maturity is particularly important, as it strongly influences population model estimates of sustainable harvest rates (Clark 1991) and, along with mean body size, is an important predictor of the risk of overexploitation (Reynolds et al. 2005). For many U.S. west coast groundfish stocks, data on age and length at maturity is of poor quality. The age at maturity curves used in many stock assessments are currently based on macroscopic (visual) assessment of ovary condition. However, there is abundant evidence that histological evaluation of ovarian thin-sections, especially if combined with optimal seasonal sampling, is much more accurate (Gunderson et al. 1980, Wyllie Echeverria 1987, West 1990, Nichol and Pikitch 1994, Hannah and Parker 2007). The age data that have been used to develop curves of age at maturity for some species is also based on outdated ageing methods, such as surface aging of otoliths, as opposed to the more accurate “break and burn” technique (Barss 1989, Wyllie Echeverria 1987, Chilton and Beamish 1982). For other species, such as cabezon (Scorpaenichthys marmoratus), accurate age and growth data, based on thin-sectioning of otoliths, have just recently been developed (Grebel and Cailliet 2003). Information on age and length at maturity that is based on histological evaluation of maturity status and modern ageing techniques is therefore needed for many U.S. west coast groundfish species. Histology-based maturity data has been developed for some U.S. west coast groundfish species. These include darkblotched rockfish (Sebastes crameri, Nichol and Pikitch 1994), petrale sole (Eopsetta jordani, Hannah et al. 2002), greenstriped rockfish (Sebastes elongatus, Shaw and Gunderson 2006), Pacific ocean perch (Sebastes alutus, Hannah and Parker 2007) and rosethorn rockfish (Sebastes helvomaculatus, Shaw and Gunderson 2008). We report here on the development of similar data for female yelloweye rockfish (Sebastes rubberimus) and cabezon. Close

• 28. [Article] Exploring functional links between circadian clocks, neurodegeneration, and aging in Drosophila melanogaster

  Circadian clocks are endogenous molecular mechanisms that coordinate daily rhythms in gene expression, cellular activities, and physiological functions with external day/night cycles. Breakdown of circadian ...

  Citation × Citation Citation Abstract Copy Title: Exploring functional links between circadian clocks, neurodegeneration, and aging in Drosophila melanogaster Author: Rakshit, Kuntol Circadian clocks are endogenous molecular mechanisms that coordinate daily rhythms in gene expression, cellular activities, and physiological functions with external day/night cycles. Breakdown of circadian rhythms such as sleep/wake cycles is associated with the onset of several neurological diseases; however, it is not clear whether disruption of rhythms is a symptom or cause of neurodegeneration, or both. To address this important question, circadian rhythms were disrupted by both genetic and environmental manipulations in Drosophila mutants prone to neurodegeneration. This led to shortening of lifespan, premature accumulation of oxidative and nervous damage during aging, and overall decline in healthspan, suggesting that circadian clocks may be causally involved in neuroprotective pathways in aging Drosophila. Recent evidence suggests bidirectional relationships between circadian rhythms and aging. While disruption of the clock mechanism accelerates aging and age-related pathologies in mammals, output rhythms of sleep and hormonal fluctuations tend to deteriorate during aging in humans, rodents, and fruit flies. To understand whether this decay is caused by defects in the core transcriptional clock, or weakening of the clock output pathways, a comprehensive study on age-related changes in the behavioral and molecular circadian rhythms was conducted using the fruit fly as a model organism. Aging caused disruption of rest/activity patterns and lengthening of the free-running period of the circadian locomotor activity rhythm. Transcriptional oscillations of four genes involved in the clock mechanism, period, timeless, Par domain protein 1ε, and vrille, were significantly reduced in heads, but not in bodies of aging flies. It was further determined that reduced transcription of these genes is not caused by the deficient expression of their activators, encoded by Clock and cycle genes. Moreover, transcriptional activation by CLOCK-CYCLE complexes is impaired despite reduced levels of the PERIOD repressor protein in old flies. These data suggest that aging alters the properties of the core transcriptional clock in flies such that both the positive and the negative limbs of the clock are attenuated. In fruit flies, the protein CRYPTOCHROME (CRY) acts in a cell-autonomous manner to synchronize circadian oscillations with light-dark cycles. The oscillatory amplitude of CRY is significantly dampened in heads of old flies at both mRNA and protein levels. Rescue of CRY using the binary GAL4/UAS system in old flies significantly enhanced the dampened molecular oscillations of several clock genes, and also strengthened the locomotor activity rhythms. There was a remarkable extension of healthspan in flies with elevated CRY. Conversely, CRY deficient mutants accumulated greater oxidative damage and showed accelerated functional decline. Interestingly, rescue of CRY in central clock neurons alone was not sufficient to restore rest/activity rhythms or extend healthspan. These data suggest novel anti-aging functions of CRY and indicate that peripheral clocks play an active role in delaying behavioral and physiological aging. Taken together, research conducted for this dissertation is a first attempt to elucidate functional links between circadian clocks, neurodegeneration, and aging. While previous evidence linking these processes was of correlative nature, functional studies conducted in this dissertation demonstrate that disruption of circadian clocks causes neurodegeneration and aging. While aging disrupts circadian rhythms at the molecular and behavioral levels, restoration of these rhythms can delay aging and improve healthspan in Drosophila. Owing to the conserved nature of clocks, novel insights obtained from this research can illuminate future translational research aimed to extend human healthspan. Title: Exploring functional links between circadian clocks, neurodegeneration, and aging in Drosophila melanogaster Author: Rakshit, Kuntol Circadian clocks are endogenous molecular mechanisms that coordinate daily rhythms in gene expression, cellular activities, and physiological functions with external day/night cycles. Breakdown of circadian rhythms such as sleep/wake cycles is associated with the onset of several neurological diseases; however, it is not clear whether disruption of rhythms is a symptom or cause of neurodegeneration, or both. To address this important question, circadian rhythms were disrupted by both genetic and environmental manipulations in Drosophila mutants prone to neurodegeneration. This led to shortening of lifespan, premature accumulation of oxidative and nervous damage during aging, and overall decline in healthspan, suggesting that circadian clocks may be causally involved in neuroprotective pathways in aging Drosophila. Recent evidence suggests bidirectional relationships between circadian rhythms and aging. While disruption of the clock mechanism accelerates aging and age-related pathologies in mammals, output rhythms of sleep and hormonal fluctuations tend to deteriorate during aging in humans, rodents, and fruit flies. To understand whether this decay is caused by defects in the core transcriptional clock, or weakening of the clock output pathways, a comprehensive study on age-related changes in the behavioral and molecular circadian rhythms was conducted using the fruit fly as a model organism. Aging caused disruption of rest/activity patterns and lengthening of the free-running period of the circadian locomotor activity rhythm. Transcriptional oscillations of four genes involved in the clock mechanism, period, timeless, Par domain protein 1ε, and vrille, were significantly reduced in heads, but not in bodies of aging flies. It was further determined that reduced transcription of these genes is not caused by the deficient expression of their activators, encoded by Clock and cycle genes. Moreover, transcriptional activation by CLOCK-CYCLE complexes is impaired despite reduced levels of the PERIOD repressor protein in old flies. These data suggest that aging alters the properties of the core transcriptional clock in flies such that both the positive and the negative limbs of the clock are attenuated. In fruit flies, the protein CRYPTOCHROME (CRY) acts in a cell-autonomous manner to synchronize circadian oscillations with light-dark cycles. The oscillatory amplitude of CRY is significantly dampened in heads of old flies at both mRNA and protein levels. Rescue of CRY using the binary GAL4/UAS system in old flies significantly enhanced the dampened molecular oscillations of several clock genes, and also strengthened the locomotor activity rhythms. There was a remarkable extension of healthspan in flies with elevated CRY. Conversely, CRY deficient mutants accumulated greater oxidative damage and showed accelerated functional decline. Interestingly, rescue of CRY in central clock neurons alone was not sufficient to restore rest/activity rhythms or extend healthspan. These data suggest novel anti-aging functions of CRY and indicate that peripheral clocks play an active role in delaying behavioral and physiological aging. Taken together, research conducted for this dissertation is a first attempt to elucidate functional links between circadian clocks, neurodegeneration, and aging. While previous evidence linking these processes was of correlative nature, functional studies conducted in this dissertation demonstrate that disruption of circadian clocks causes neurodegeneration and aging. While aging disrupts circadian rhythms at the molecular and behavioral levels, restoration of these rhythms can delay aging and improve healthspan in Drosophila. Owing to the conserved nature of clocks, novel insights obtained from this research can illuminate future translational research aimed to extend human healthspan. Close

• 29. [Article] A study of the perceptual parameters of voice in aging females

  An interest in understanding the aging processes, as they relate to voice, has prompted research investigating physiological, acoustical, and perceptual attributes of the aging vocal mechanism. Recently, ...

  Citation × Citation Citation Abstract Copy Title: A study of the perceptual parameters of voice in aging females Author: Mathers, Barbara Ann Year: 1978 An interest in understanding the aging processes, as they relate to voice, has prompted research investigating physiological, acoustical, and perceptual attributes of the aging vocal mechanism. Recently, it has been demonstrated that perceptual parameters, in older male voices, differentiate speakers according to age estimations, as determined by a group of listeners. The purpose of this study was to determine the perceptual characteristics of the female voice which are associated with perceived age, as contrasted to chronological age. Title: A study of the perceptual parameters of voice in aging females Author: Mathers, Barbara Ann Year: 1978 An interest in understanding the aging processes, as they relate to voice, has prompted research investigating physiological, acoustical, and perceptual attributes of the aging vocal mechanism. Recently, it has been demonstrated that perceptual parameters, in older male voices, differentiate speakers according to age estimations, as determined by a group of listeners. The purpose of this study was to determine the perceptual characteristics of the female voice which are associated with perceived age, as contrasted to chronological age. Close

• 30. [Article] Age and the comprehension of spatial adjectives

  The purpose of this study was to determine the significance of chronological age on the comprehension of spatial adjectives in children. Specifically, the investigation set out to determine the age levels ...

  Citation × Citation Citation Abstract Copy Title: Age and the comprehension of spatial adjectives Author: Cassidy, Barbara Ann Year: 1980 The purpose of this study was to determine the significance of chronological age on the comprehension of spatial adjectives in children. Specifically, the investigation set out to determine the age levels at which children comprehend the polar forms of various spatial adjectives and to determine the difference in age levels of comprehension of unmarked versus marked adjective forms. Seventy children between the ages of two years, +/-2 months and eight years, + 2 months, selected on the basis of chronological age, normal receptive vocabulary recognition and normal hearing, participated as subjects. Title: Age and the comprehension of spatial adjectives Author: Cassidy, Barbara Ann Year: 1980 The purpose of this study was to determine the significance of chronological age on the comprehension of spatial adjectives in children. Specifically, the investigation set out to determine the age levels at which children comprehend the polar forms of various spatial adjectives and to determine the difference in age levels of comprehension of unmarked versus marked adjective forms. Seventy children between the ages of two years, +/-2 months and eight years, + 2 months, selected on the basis of chronological age, normal receptive vocabulary recognition and normal hearing, participated as subjects. Close