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• 1. [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

• 2. [Article] Exploring reproductive signaling using nonconventional aquatic models: aging and reproductive function in killifish and sea anemones

  Aquatic animals possess surprising similarities to humans in reproductive signaling that are simplified or elaborated for life underwater, making them useful for studying reproductive control. In this ...

  Citation × Citation Citation Abstract Copy Title: Exploring reproductive signaling using nonconventional aquatic models: aging and reproductive function in killifish and sea anemones Author: Ferguson, Lindsey G. Aquatic animals possess surprising similarities to humans in reproductive signaling that are simplified or elaborated for life underwater, making them useful for studying reproductive control. In this thesis, killifish and sea anemones are used as models for reproductive function and aging. The aging model Nothobranchius (killifish) was used to investigate circadian rhythms and clock gene expression in reproductive tissues, and effects of the anti-aging compound resveratrol (RSV) were examined to elucidate the role of clock genes in fertility. Weak connections were found between gonadal clock gene expression and age, and RSV altered expression over time and shifted rhythmic patterns in old fish, suggesting that it may modulate circadian rhythms with age. Additionally, to understand the physiological mechanisms behind coral spawning for conservation and elucidate hormonal evolution, functions of the cnidarian leucine-rich repeat-containing G protein-coupled receptor LGRA2 were investigated in the model sea anemone Aiptasia pallida. LGRA2 was expressed near gonadal regions of sexually developed sea anemones, activated by gonadotropins, and modulated by estrogen, indicating that it is involved in regulating reproduction similarly to its mammalian homologs luteinizing hormone receptor and follicle stimulating hormone receptor. These projects together provide a One Health view of reproductive signaling and aging. Title: Exploring reproductive signaling using nonconventional aquatic models: aging and reproductive function in killifish and sea anemones Author: Ferguson, Lindsey G. Aquatic animals possess surprising similarities to humans in reproductive signaling that are simplified or elaborated for life underwater, making them useful for studying reproductive control. In this thesis, killifish and sea anemones are used as models for reproductive function and aging. The aging model Nothobranchius (killifish) was used to investigate circadian rhythms and clock gene expression in reproductive tissues, and effects of the anti-aging compound resveratrol (RSV) were examined to elucidate the role of clock genes in fertility. Weak connections were found between gonadal clock gene expression and age, and RSV altered expression over time and shifted rhythmic patterns in old fish, suggesting that it may modulate circadian rhythms with age. Additionally, to understand the physiological mechanisms behind coral spawning for conservation and elucidate hormonal evolution, functions of the cnidarian leucine-rich repeat-containing G protein-coupled receptor LGRA2 were investigated in the model sea anemone Aiptasia pallida. LGRA2 was expressed near gonadal regions of sexually developed sea anemones, activated by gonadotropins, and modulated by estrogen, indicating that it is involved in regulating reproduction similarly to its mammalian homologs luteinizing hormone receptor and follicle stimulating hormone receptor. These projects together provide a One Health view of reproductive signaling and aging. Close

• 3. [Article] An Accumulation of Senescent Cells May Contribute to Chronic Inflammation of the Mammalian Liver

  The aging process is a biological phenomenon in mammals that heavily contributes to the onset of chronic diseases. While there are many theories that attempt to explain the biological onset of aging, one ...

  Citation × Citation Citation Abstract Copy Title: An Accumulation of Senescent Cells May Contribute to Chronic Inflammation of the Mammalian Liver Author: Sugiyama, Aaron The aging process is a biological phenomenon in mammals that heavily contributes to the onset of chronic diseases. While there are many theories that attempt to explain the biological onset of aging, one emerging theory involves chronic inflammation. Chronic inflammation has been previously linked to several age-related diseases and is a known driver of chronic inflammation. To examine chronic inflammation and cellular senescence in the context of aging, we examined hepatocytes harvested from rat livers as a model. We found that rat hepatocytes not only undergo cellular senescence, but that senescent cells accumulate with age. This accumulation of senescent cells with age was also accompanied by a large increase in miR-146a and miR-155 (a seven fold and a forty-five fold change respectively) in the old rat exosomes, which indicate chronic inflammatory insult. These findings corroborate with our findings regarding an accumulation of senescent cells in the liver, and suggests that the liver undergoes an inflammatory stress. We then examined a possible treatment for cellular senescence: the drug known as dasatinib. Title: An Accumulation of Senescent Cells May Contribute to Chronic Inflammation of the Mammalian Liver Author: Sugiyama, Aaron The aging process is a biological phenomenon in mammals that heavily contributes to the onset of chronic diseases. While there are many theories that attempt to explain the biological onset of aging, one emerging theory involves chronic inflammation. Chronic inflammation has been previously linked to several age-related diseases and is a known driver of chronic inflammation. To examine chronic inflammation and cellular senescence in the context of aging, we examined hepatocytes harvested from rat livers as a model. We found that rat hepatocytes not only undergo cellular senescence, but that senescent cells accumulate with age. This accumulation of senescent cells with age was also accompanied by a large increase in miR-146a and miR-155 (a seven fold and a forty-five fold change respectively) in the old rat exosomes, which indicate chronic inflammatory insult. These findings corroborate with our findings regarding an accumulation of senescent cells in the liver, and suggests that the liver undergoes an inflammatory stress. We then examined a possible treatment for cellular senescence: the drug known as dasatinib. Close

• 4. [Article] Accelerated food source location in aging Drosophila

  Adequate energy stores are essential for animal survival, and sophisticated neuroendocrine mechanisms evolved to stimulate foraging in response to nutrient deprivation. Food search behavior is usually ...

  Citation × Citation Citation Abstract Copy Title: Accelerated food source location in aging Drosophila Author: Egenriether, Sada Adequate energy stores are essential for animal survival, and sophisticated neuroendocrine mechanisms evolved to stimulate foraging in response to nutrient deprivation. Food search behavior is usually investigated in young animals, and it is not known how aging alters this behavior. To address this question in Drosophila, we compared the ability to locate food by olfaction in young and old flies using a food-filled trap. As aging is associated with decline in motor functions, learning, and memory, we expected that aged flies would take longer to enter the food trap than their young counterparts. Surprisingly, old flies located food with significantly shorter latency than the young ones. We determined that old flies have significantly lower fat reserves and are more susceptible to starvation than young flies. Food search latency was shortened in young wild type flies that were starved until their fat was depleted. We also determined that the difference in food finding latency (FFL) between young and old flies is mediated by insulin signaling. Together, our data suggest that shorter FFL in old flies is linked to age-dependent differences in metabolic status. Title: Accelerated food source location in aging Drosophila Author: Egenriether, Sada Adequate energy stores are essential for animal survival, and sophisticated neuroendocrine mechanisms evolved to stimulate foraging in response to nutrient deprivation. Food search behavior is usually investigated in young animals, and it is not known how aging alters this behavior. To address this question in Drosophila, we compared the ability to locate food by olfaction in young and old flies using a food-filled trap. As aging is associated with decline in motor functions, learning, and memory, we expected that aged flies would take longer to enter the food trap than their young counterparts. Surprisingly, old flies located food with significantly shorter latency than the young ones. We determined that old flies have significantly lower fat reserves and are more susceptible to starvation than young flies. Food search latency was shortened in young wild type flies that were starved until their fat was depleted. We also determined that the difference in food finding latency (FFL) between young and old flies is mediated by insulin signaling. Together, our data suggest that shorter FFL in old flies is linked to age-dependent differences in metabolic status. Close

• 5. [Article] The Effects of the Immunity Factor Relish on Aging Phenotypes in Drosophila melanogaster

  Access to this item has been restricted by repository administrators at the request of the author until March 8, 2017.

  Citation × Citation Citation Abstract Copy Title: The Effects of the Immunity Factor Relish on Aging Phenotypes in Drosophila melanogaster Author: Kumar, Nandita Access to this item has been restricted by repository administrators at the request of the author until March 8, 2017. Title: The Effects of the Immunity Factor Relish on Aging Phenotypes in Drosophila melanogaster Author: Kumar, Nandita Access to this item has been restricted by repository administrators at the request of the author until March 8, 2017. Close

• 6. [Article] Effects of aging on the effectiveness of smoking cessation medication

  This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Impact Journals. The published article can be found at: http://www.impactjournals.com/oncotarge...

  Citation × Citation Citation Abstract Copy Title: Effects of aging on the effectiveness of smoking cessation medication Author: Junior Lima Santos, Paulo Caleb, Pereira, Alexandre Costa, Scholz, Jaqueline, Pierri, Humberto, Buzo, Carolina Giusti, Moreira Lopes, Neuza Helena, Gaya, Patricia Viviane, Amorim, Clarice, Ogawa Abe, Tania Marie This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Impact Journals. The published article can be found at: http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget Title: Effects of aging on the effectiveness of smoking cessation medication Author: Junior Lima Santos, Paulo Caleb, Pereira, Alexandre Costa, Scholz, Jaqueline, Pierri, Humberto, Buzo, Carolina Giusti, Moreira Lopes, Neuza Helena, Gaya, Patricia Viviane, Amorim, Clarice, Ogawa Abe, Tania Marie This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Impact Journals. The published article can be found at: http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget Close

• 7. [Article] Consequences of miRNA misregulation on embryonic development and aging

  microRNAs (miRNAs), ~21-24 nucleotide-long RNAs that post-transcriptionally regulate gene expression, have rapidly become one of the most extensively studied mechanisms of the past decade. Since their ...

  Citation × Citation Citation Abstract Copy Title: Consequences of miRNA misregulation on embryonic development and aging Author: Franzosa, Jill A. microRNAs (miRNAs), ~21-24 nucleotide-long RNAs that post-transcriptionally regulate gene expression, have rapidly become one of the most extensively studied mechanisms of the past decade. Since their discovery as temporal regulators of post-embryonic development in C. elegans, miRNAs have been functionally implicated in almost every cellular process investigated to date. miRNAs are integral to the complex biological processes of embryonic development and aging. In this research, we sought to determine whether misregulation of miRNAs could be responsible for eliciting adverse effects during these two distinct developmental stages. First, to uncover the potential role of miRNAs in teratogenicity, we investigated whether miRNAs were involved in regulation of retinoic acid (RA) induced vertebrate axis defects. Global miRNA expression profiling revealed that RA exposure suppressed the expression of miR-19 family members during zebrafish somitogenesis. Bioinformatics analyses predict that miR-19 targets cyp26a1, a key RA detoxifying enzyme, and a physiological reporter assay confirmed that cyp26a1 is a bona fide target of miR-19. Transient knockdown of miR-19 phenocopied RA-induced body axis defects. In gain-of-function studies, exogenous miR-19 rescued the axis defects caused by RA exposure. Our findings indicate that the teratogenic effects of RA exposure result, in part, from repression of miR-19 and the subsequent misregulation of cyp26a1. This highlights a previously unidentified role of miR-19 in facilitating vertebrate axis development. Next, to explore whether age-related changes in miRNAs trigger deficits in regeneration capacity, we performed mRNA and small RNA sequencing on regenerating and non-regenerating caudal fin tissue from aged, adult and juvenile zebrafish. An unbiased approach identified cbx7 as the most abundant transcript with significantly increased expression in regenerative-competent adult and juvenile tissue and decreased expression in regenerative-compromised aged tissue. While cbx7 is a known regulator of aging, this is the first report of its role in tissue regeneration. A computational approach was used to discover mRNAs expressed during regeneration, which are potential targets of the significantly expressed miRNAs in regenerating tissue. miR-21 was one of the most abundant and significantly increased miRNAs in regenerating tissue and exhibited an aberrant age-dependent expression profile. Bioinformatics predicts miR-21 to target the 3' UTR of cbx7 and a reporter assay confirmed that miR-21 targets cbx7 in vivo. Transient knockdown of miR-21 inhibited tissue regeneration, suggesting a role for miRNA mediated regulation of cbx7 during regeneration. These findings reveal a novel, age-dependent regenerative function of cbx7 and emphasize the importance of miR-21 as a master regulator of vertebrate regenerative responses. This research, when combined, underscores the negative consequences misregulation of miRNAs has on embryonic development and aging. Title: Consequences of miRNA misregulation on embryonic development and aging Author: Franzosa, Jill A. microRNAs (miRNAs), ~21-24 nucleotide-long RNAs that post-transcriptionally regulate gene expression, have rapidly become one of the most extensively studied mechanisms of the past decade. Since their discovery as temporal regulators of post-embryonic development in C. elegans, miRNAs have been functionally implicated in almost every cellular process investigated to date. miRNAs are integral to the complex biological processes of embryonic development and aging. In this research, we sought to determine whether misregulation of miRNAs could be responsible for eliciting adverse effects during these two distinct developmental stages. First, to uncover the potential role of miRNAs in teratogenicity, we investigated whether miRNAs were involved in regulation of retinoic acid (RA) induced vertebrate axis defects. Global miRNA expression profiling revealed that RA exposure suppressed the expression of miR-19 family members during zebrafish somitogenesis. Bioinformatics analyses predict that miR-19 targets cyp26a1, a key RA detoxifying enzyme, and a physiological reporter assay confirmed that cyp26a1 is a bona fide target of miR-19. Transient knockdown of miR-19 phenocopied RA-induced body axis defects. In gain-of-function studies, exogenous miR-19 rescued the axis defects caused by RA exposure. Our findings indicate that the teratogenic effects of RA exposure result, in part, from repression of miR-19 and the subsequent misregulation of cyp26a1. This highlights a previously unidentified role of miR-19 in facilitating vertebrate axis development. Next, to explore whether age-related changes in miRNAs trigger deficits in regeneration capacity, we performed mRNA and small RNA sequencing on regenerating and non-regenerating caudal fin tissue from aged, adult and juvenile zebrafish. An unbiased approach identified cbx7 as the most abundant transcript with significantly increased expression in regenerative-competent adult and juvenile tissue and decreased expression in regenerative-compromised aged tissue. While cbx7 is a known regulator of aging, this is the first report of its role in tissue regeneration. A computational approach was used to discover mRNAs expressed during regeneration, which are potential targets of the significantly expressed miRNAs in regenerating tissue. miR-21 was one of the most abundant and significantly increased miRNAs in regenerating tissue and exhibited an aberrant age-dependent expression profile. Bioinformatics predicts miR-21 to target the 3' UTR of cbx7 and a reporter assay confirmed that miR-21 targets cbx7 in vivo. Transient knockdown of miR-21 inhibited tissue regeneration, suggesting a role for miRNA mediated regulation of cbx7 during regeneration. These findings reveal a novel, age-dependent regenerative function of cbx7 and emphasize the importance of miR-21 as a master regulator of vertebrate regenerative responses. This research, when combined, underscores the negative consequences misregulation of miRNAs has on embryonic development and aging. Close

• 8. [Article] Do Hassles and Uplifts Change with Age? Longitudinal Findings from the NAS

  This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by American Psychological Association and can be found at: http://www.apa.org/pubs/journals/pag/index.aspx. This ...

  Citation × Citation Citation Abstract Copy Title: Do Hassles and Uplifts Change with Age? Longitudinal Findings from the NAS Author: Aldwin, Carolyn M., Jeong, Yu-Jin, Igarashi, Heidi, Spiro, Avron, III This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by American Psychological Association and can be found at: http://www.apa.org/pubs/journals/pag/index.aspx. This article may not exactly replicate the final version published in the APA journal. It is not the copy of record. Title: Do Hassles and Uplifts Change with Age? Longitudinal Findings from the NAS Author: Aldwin, Carolyn M., Jeong, Yu-Jin, Igarashi, Heidi, Spiro, Avron, III This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by American Psychological Association and can be found at: http://www.apa.org/pubs/journals/pag/index.aspx. This article may not exactly replicate the final version published in the APA journal. It is not the copy of record. Close

• 9. [Article] 2012 LIFE Scholars.pptx

  Citation × Citation Citation Abstract Copy Title: 2012 LIFE Scholars.pptx Author: Egenriether, Sada Title: 2012 LIFE Scholars.pptx Author: Egenriether, Sada Close

• 10. [Article] 2012 LIFE Scholars.pdf

  Citation × Citation Citation Abstract Copy Title: 2012 LIFE Scholars.pdf Author: Egenriether, Sada Title: 2012 LIFE Scholars.pdf Author: Egenriether, Sada Close