The Experts below are selected from a list of 204 Experts worldwide ranked by ideXlab platform
Justin S Rhodes - One of the best experts on this subject based on the ideXlab platform.
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voluntary wheel running has no impact on brain and liver mitochondrial dna copy number or mutation measures in the polg mouse Model of Aging
PLOS ONE, 2020Co-Authors: Kendra D Maclaine, Kevin A Stebbings, Daniel A Llano, Justin S RhodesAbstract:The mitochondrial theory of Aging attributes much of the Aging process to mitochondrial DNA damage. The polymerase gamma (PolG) mutant mouse was designed to evaluate this theory and thus carries a mutated proofreading region of polymerase gamma (D257A) that exclusively transcribes the mitochondrial genome. As a result, PolGD257A mice accumulate mitochondrial DNA (mtDNA) mutations that lead to premature Aging, as evidenced by hair loss, weight loss, kyphosis, increased rates of apoptosis, organ damage, and an early death, occurring around 12 months of age. Research has shown that exercise decreases skeletal muscle mtDNA mutations and normalizes protein levels in PolG mice. However, brain mtDNA changes with exercise in PolG mice have not been studied. We found no effects of exercise on mtDNA mutations or copy number in either the brain or liver of PolG mice, despite changes to body mass. Our results suggest that mitochondrial mutations play little role in exercise-brain interactions in the PolG Model of accelerated Aging. In addition to evaluating the effect of exercise on mtDNA outcomes, we also implemented novel methods for both extracting mtDNA and measuring mtDNA mutations, with aims for improving the efficiency and accuracy of these methods.
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voluntary wheel running has no impact on brain and liver mitochondrial dna copy number or mutation measures in the polg mouse Model of Aging
bioRxiv, 2019Co-Authors: Kendra D Maclaine, Kevin A Stebbings, Daniel A Llano, Justin S RhodesAbstract:The mitochondrial theory of Aging attributes much of the Aging process to mitochondrial DNA damage. The PolGA D257A/D257A (PolG) mutant mouse was created to explore the mitochondrial theory of Aging and carries a mutated proofreading region of polymerase gamma, which exclusively transcribes the mitochondrial genome. As a result, PolG mice accumulate mitochondrial DNA (mtDNA) mutations which leads to premature Aging including hair loss, weight loss, kyphosis, increased rates of apoptosis, organ damage, and eventually, an early death at around 12 months. Exercise has been reported to decrease skeletal muscle mtDNA mutations and normalize protein levels in PolG mice. However, brain mtDNA changes with exercise in PolG mice have not been explored. We found no effects of exercise on mtDNA mutations or copy number in brain or liver in PolG mice, despite effects on body mass. Our results suggest that mitochondrial mutations play little role in exercise-brain interactions in the PolG Model of accelerated Aging. In addition to evaluating the effect of exercise on mtDNA outcomes, we also implemented novel methods for mtDNA extraction and measuring mtDNA mutations to improve efficiency and accuracy.
Toshitaka Nabeshima - One of the best experts on this subject based on the ideXlab platform.
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Inactivation of JAK2/STAT3 Signaling Axis and Downregulation of M1 mAChR Cause Cognitive Impairment in klotho Mutant Mice, a Genetic Model of Aging
Neuropsychopharmacology, 2013Co-Authors: Seok-joo Park, Yoichi Nabeshima, Eun-joo Shin, Jihua An, Zhengyi Li, Yoon Hee Chung, Ji Hoon Jeong, Jae-hyung Bach, Choon-gon Jang, Toshitaka NabeshimaAbstract:We previously reported cognitive dysfunction in klotho mutant mice. In the present study, we further examined novel mechanisms involved in cognitive impairment in these mice. Significantly decreased janus kinase 2 (JAK2) and signal transducer and activator of transcription3 (STAT3) phosphorylation were observed in the hippocampus of klotho mutant mice. A selective decrease in protein expression and binding density of the M1 muscarinic cholinergic receptor (M1 mAChR) was observed in these mice. Cholinergic parameters (ie, acetylcholine (ACh), choline acetyltransferase (ChAT), and acetylcholinesterase (AChE)) and NMDAR-dependent long-term potentiation (LTP) were significantly impaired in klotho mutant mice. McN-A-343 (McN), an M1 mAChR agonist, significantly attenuated these impairments. AG490 (AG), a JAK2 inhibitor, counteracted the attenuating effects of McN, although AG did not significantly alter the McN-induced effect on AChE. Furthermore, AG significantly inhibited the attenuating effects of McN on decreased NMDAR-dependent LTP, protein kinase C β II, p-ERK, p-CREB, BDNF, and p-JAK2/p-STAT3-expression in klotho mutant mice. In addition, k252a, a BDNF receptor tyrosine kinase B (TrkB) inhibitor, significantly counteracted McN effects on decreased ChAT, ACh, and M1 mAChR and p-JAK2/p-STAT3 expression. McN-induced effects on cognitive impairment in klotho mutant mice were consistently counteracted by either AG or k252a. Our results suggest that inactivation of the JAK2/STAT3 signaling axis and M1 mAChR downregulation play a critical role in cognitive impairment observed in klotho mutant mice.
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cognition impairment in the genetic Model of Aging klotho gene mutant mice a role of oxidative stress
The FASEB Journal, 2003Co-Authors: Taku Nagai, Kiyofumi Yamada, Yukihiro Noda, Akihiro Imura, Yoichi Nabeshima, Toshitaka NabeshimaAbstract:SPECIFIC AIMSAlthough a new gene, termed klotho, is associated with the suppression of several Aging phenotypes, little is known about its function in the brain. We investigated the changes in mnem...
Kendra D Maclaine - One of the best experts on this subject based on the ideXlab platform.
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voluntary wheel running has no impact on brain and liver mitochondrial dna copy number or mutation measures in the polg mouse Model of Aging
PLOS ONE, 2020Co-Authors: Kendra D Maclaine, Kevin A Stebbings, Daniel A Llano, Justin S RhodesAbstract:The mitochondrial theory of Aging attributes much of the Aging process to mitochondrial DNA damage. The polymerase gamma (PolG) mutant mouse was designed to evaluate this theory and thus carries a mutated proofreading region of polymerase gamma (D257A) that exclusively transcribes the mitochondrial genome. As a result, PolGD257A mice accumulate mitochondrial DNA (mtDNA) mutations that lead to premature Aging, as evidenced by hair loss, weight loss, kyphosis, increased rates of apoptosis, organ damage, and an early death, occurring around 12 months of age. Research has shown that exercise decreases skeletal muscle mtDNA mutations and normalizes protein levels in PolG mice. However, brain mtDNA changes with exercise in PolG mice have not been studied. We found no effects of exercise on mtDNA mutations or copy number in either the brain or liver of PolG mice, despite changes to body mass. Our results suggest that mitochondrial mutations play little role in exercise-brain interactions in the PolG Model of accelerated Aging. In addition to evaluating the effect of exercise on mtDNA outcomes, we also implemented novel methods for both extracting mtDNA and measuring mtDNA mutations, with aims for improving the efficiency and accuracy of these methods.
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voluntary wheel running has no impact on brain and liver mitochondrial dna copy number or mutation measures in the polg mouse Model of Aging
bioRxiv, 2019Co-Authors: Kendra D Maclaine, Kevin A Stebbings, Daniel A Llano, Justin S RhodesAbstract:The mitochondrial theory of Aging attributes much of the Aging process to mitochondrial DNA damage. The PolGA D257A/D257A (PolG) mutant mouse was created to explore the mitochondrial theory of Aging and carries a mutated proofreading region of polymerase gamma, which exclusively transcribes the mitochondrial genome. As a result, PolG mice accumulate mitochondrial DNA (mtDNA) mutations which leads to premature Aging including hair loss, weight loss, kyphosis, increased rates of apoptosis, organ damage, and eventually, an early death at around 12 months. Exercise has been reported to decrease skeletal muscle mtDNA mutations and normalize protein levels in PolG mice. However, brain mtDNA changes with exercise in PolG mice have not been explored. We found no effects of exercise on mtDNA mutations or copy number in brain or liver in PolG mice, despite effects on body mass. Our results suggest that mitochondrial mutations play little role in exercise-brain interactions in the PolG Model of accelerated Aging. In addition to evaluating the effect of exercise on mtDNA outcomes, we also implemented novel methods for mtDNA extraction and measuring mtDNA mutations to improve efficiency and accuracy.
Kevin A Stebbings - One of the best experts on this subject based on the ideXlab platform.
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voluntary wheel running has no impact on brain and liver mitochondrial dna copy number or mutation measures in the polg mouse Model of Aging
PLOS ONE, 2020Co-Authors: Kendra D Maclaine, Kevin A Stebbings, Daniel A Llano, Justin S RhodesAbstract:The mitochondrial theory of Aging attributes much of the Aging process to mitochondrial DNA damage. The polymerase gamma (PolG) mutant mouse was designed to evaluate this theory and thus carries a mutated proofreading region of polymerase gamma (D257A) that exclusively transcribes the mitochondrial genome. As a result, PolGD257A mice accumulate mitochondrial DNA (mtDNA) mutations that lead to premature Aging, as evidenced by hair loss, weight loss, kyphosis, increased rates of apoptosis, organ damage, and an early death, occurring around 12 months of age. Research has shown that exercise decreases skeletal muscle mtDNA mutations and normalizes protein levels in PolG mice. However, brain mtDNA changes with exercise in PolG mice have not been studied. We found no effects of exercise on mtDNA mutations or copy number in either the brain or liver of PolG mice, despite changes to body mass. Our results suggest that mitochondrial mutations play little role in exercise-brain interactions in the PolG Model of accelerated Aging. In addition to evaluating the effect of exercise on mtDNA outcomes, we also implemented novel methods for both extracting mtDNA and measuring mtDNA mutations, with aims for improving the efficiency and accuracy of these methods.
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voluntary wheel running has no impact on brain and liver mitochondrial dna copy number or mutation measures in the polg mouse Model of Aging
bioRxiv, 2019Co-Authors: Kendra D Maclaine, Kevin A Stebbings, Daniel A Llano, Justin S RhodesAbstract:The mitochondrial theory of Aging attributes much of the Aging process to mitochondrial DNA damage. The PolGA D257A/D257A (PolG) mutant mouse was created to explore the mitochondrial theory of Aging and carries a mutated proofreading region of polymerase gamma, which exclusively transcribes the mitochondrial genome. As a result, PolG mice accumulate mitochondrial DNA (mtDNA) mutations which leads to premature Aging including hair loss, weight loss, kyphosis, increased rates of apoptosis, organ damage, and eventually, an early death at around 12 months. Exercise has been reported to decrease skeletal muscle mtDNA mutations and normalize protein levels in PolG mice. However, brain mtDNA changes with exercise in PolG mice have not been explored. We found no effects of exercise on mtDNA mutations or copy number in brain or liver in PolG mice, despite effects on body mass. Our results suggest that mitochondrial mutations play little role in exercise-brain interactions in the PolG Model of accelerated Aging. In addition to evaluating the effect of exercise on mtDNA outcomes, we also implemented novel methods for mtDNA extraction and measuring mtDNA mutations to improve efficiency and accuracy.
Daniel A Llano - One of the best experts on this subject based on the ideXlab platform.
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voluntary wheel running has no impact on brain and liver mitochondrial dna copy number or mutation measures in the polg mouse Model of Aging
PLOS ONE, 2020Co-Authors: Kendra D Maclaine, Kevin A Stebbings, Daniel A Llano, Justin S RhodesAbstract:The mitochondrial theory of Aging attributes much of the Aging process to mitochondrial DNA damage. The polymerase gamma (PolG) mutant mouse was designed to evaluate this theory and thus carries a mutated proofreading region of polymerase gamma (D257A) that exclusively transcribes the mitochondrial genome. As a result, PolGD257A mice accumulate mitochondrial DNA (mtDNA) mutations that lead to premature Aging, as evidenced by hair loss, weight loss, kyphosis, increased rates of apoptosis, organ damage, and an early death, occurring around 12 months of age. Research has shown that exercise decreases skeletal muscle mtDNA mutations and normalizes protein levels in PolG mice. However, brain mtDNA changes with exercise in PolG mice have not been studied. We found no effects of exercise on mtDNA mutations or copy number in either the brain or liver of PolG mice, despite changes to body mass. Our results suggest that mitochondrial mutations play little role in exercise-brain interactions in the PolG Model of accelerated Aging. In addition to evaluating the effect of exercise on mtDNA outcomes, we also implemented novel methods for both extracting mtDNA and measuring mtDNA mutations, with aims for improving the efficiency and accuracy of these methods.
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voluntary wheel running has no impact on brain and liver mitochondrial dna copy number or mutation measures in the polg mouse Model of Aging
bioRxiv, 2019Co-Authors: Kendra D Maclaine, Kevin A Stebbings, Daniel A Llano, Justin S RhodesAbstract:The mitochondrial theory of Aging attributes much of the Aging process to mitochondrial DNA damage. The PolGA D257A/D257A (PolG) mutant mouse was created to explore the mitochondrial theory of Aging and carries a mutated proofreading region of polymerase gamma, which exclusively transcribes the mitochondrial genome. As a result, PolG mice accumulate mitochondrial DNA (mtDNA) mutations which leads to premature Aging including hair loss, weight loss, kyphosis, increased rates of apoptosis, organ damage, and eventually, an early death at around 12 months. Exercise has been reported to decrease skeletal muscle mtDNA mutations and normalize protein levels in PolG mice. However, brain mtDNA changes with exercise in PolG mice have not been explored. We found no effects of exercise on mtDNA mutations or copy number in brain or liver in PolG mice, despite effects on body mass. Our results suggest that mitochondrial mutations play little role in exercise-brain interactions in the PolG Model of accelerated Aging. In addition to evaluating the effect of exercise on mtDNA outcomes, we also implemented novel methods for mtDNA extraction and measuring mtDNA mutations to improve efficiency and accuracy.