Pub Date : 2024-02-20DOI: 10.59368/agingbio.20240026
Matthew D W Piper, Joshua N. Johnstone, C. Mirth, Travis K. Johnson, Ralf B. Schittenhelm
{"title":"GCN2 Mediates Access to Stored Amino Acids for Somatic Maintenance during Drosophila Aging","authors":"Matthew D W Piper, Joshua N. Johnstone, C. Mirth, Travis K. Johnson, Ralf B. Schittenhelm","doi":"10.59368/agingbio.20240026","DOIUrl":"https://doi.org/10.59368/agingbio.20240026","url":null,"abstract":"","PeriodicalId":72130,"journal":{"name":"Aging Biology","volume":"170 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140449133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-13DOI: 10.59368/agingbio.20240023
Cheryl A. Conover, L. Bale, Sally A. West, Claus Oxvig, Kristian S. Andersen, A. Roden, Andrew J. Haak
{"title":"Genetic and Pharmacological Inhibition of PAPP-A Reduces Bleomycin-Induced Pulmonary Fibrosis in Aged Mice via Reduced IGF Signaling","authors":"Cheryl A. Conover, L. Bale, Sally A. West, Claus Oxvig, Kristian S. Andersen, A. Roden, Andrew J. Haak","doi":"10.59368/agingbio.20240023","DOIUrl":"https://doi.org/10.59368/agingbio.20240023","url":null,"abstract":"","PeriodicalId":72130,"journal":{"name":"Aging Biology","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140457229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-03-15DOI: 10.59368/agingbio.20240024
Rebecca Choi, Rahul Bodkhe, Barbara Pees, Dan Kim, Maureen Berg, David Monnin, Juhyun Cho, Vivek Narayan, Ethan Deller, Cathy Savage-Dunn, Michael Shapira
The gut microbiome plays important roles in host function and health. Core microbiomes have been described for different species, and imbalances in their composition, known as dysbiosis, are associated with pathology. Changes in the gut microbiome and dysbiosis are common in aging, possibly due to multi-tissue deterioration, which includes metabolic shifts, dysregulated immunity, and disrupted epithelial barriers. However, the characteristics of these changes, as reported in different studies, are varied and sometimes conflicting. Using clonal populations of Caenorhabditis elegans to highlight trends shared among individuals, we employed 16s rRNA gene sequencing, CFU counts and fluorescent imaging, identifying an Enterobacteriaceae bloom as a common denominator in aging animals. Experiments using Enterobacter hormaechei, a representative commensal, suggested that the Enterobacteriaceae bloom was facilitated by a decline in Sma/BMP immune signaling in aging animals and demonstrated its potential for exacerbating infection susceptibility. However, such detrimental effects were context-dependent, mitigated by competition with commensal communities, highlighting the latter as determinants of healthy versus unhealthy aging, depending on their ability to restrain opportunistic pathobionts.
{"title":"An <i>Enterobacteriaceae</i> bloom in aging animals is restrained by the gut microbiome.","authors":"Rebecca Choi, Rahul Bodkhe, Barbara Pees, Dan Kim, Maureen Berg, David Monnin, Juhyun Cho, Vivek Narayan, Ethan Deller, Cathy Savage-Dunn, Michael Shapira","doi":"10.59368/agingbio.20240024","DOIUrl":"10.59368/agingbio.20240024","url":null,"abstract":"<p><p>The gut microbiome plays important roles in host function and health. Core microbiomes have been described for different species, and imbalances in their composition, known as dysbiosis, are associated with pathology. Changes in the gut microbiome and dysbiosis are common in aging, possibly due to multi-tissue deterioration, which includes metabolic shifts, dysregulated immunity, and disrupted epithelial barriers. However, the characteristics of these changes, as reported in different studies, are varied and sometimes conflicting. Using clonal populations of <i>Caenorhabditis elegans</i> to highlight trends shared among individuals, we employed 16s rRNA gene sequencing, CFU counts and fluorescent imaging, identifying an <i>Enterobacteriaceae</i> bloom as a common denominator in aging animals. Experiments using <i>Enterobacter hormaechei</i>, a representative commensal, suggested that the <i>Enterobacteriaceae</i> bloom was facilitated by a decline in Sma/BMP immune signaling in aging animals and demonstrated its potential for exacerbating infection susceptibility. However, such detrimental effects were context-dependent, mitigated by competition with commensal communities, highlighting the latter as determinants of healthy versus unhealthy aging, depending on their ability to restrain opportunistic pathobionts.</p>","PeriodicalId":72130,"journal":{"name":"Aging Biology","volume":"2 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11085993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140913576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-02-20DOI: 10.59368/agingbio.20240025
Jae-Hyeon Park, Burcin Duan Sahbaz, Komal Pekhale, Xixia Chu, Mustafa N Okur, Mhamed Grati, Kevin Isgrig, Wade Chien, Elena Chrysostomou, Lauren Sullivan, Deborah L Croteau, Uri Manor, Vilhelm A Bohr
There is considerable interest in whether sensory deficiency is associated with the development of Alzheimer's disease (AD). Notably, the relationship between hearing impairment and AD is of high relevance but still poorly understood. In this study, we found early-onset hearing loss in two AD mouse models, 3xTgAD and 3xTgAD/Polβ+/-. The 3xTgAD/Polβ+/- mouse is DNA repair deficient and has more humanized AD features than the 3xTgAD. Both AD mouse models showed increased auditory brainstem response (ABR) thresholds between 16 and 32 kHz at 4 weeks of age, much earlier than any AD cognitive and behavioral changes. The ABR thresholds were significantly higher in 3xTgAD/Polβ+/- mice than in 3xTgAD mice at 16 kHz, and distortion product otoacoustic emission signals were reduced, indicating that DNA damage may be a factor underlying early hearing impairment in AD. Poly ADP-ribosylation and protein expression levels of DNA damage markers increased significantly in the cochlea of the AD mice but not in the adjacent auditory cortex. Phosphoglycerate mutase 2 levels and the number of synaptic ribbons in the presynaptic zones of inner hair cells were decreased in the cochlea of the AD mice. Furthermore, the activity of sirtuin 3 was downregulated in the cochlea of these mice, indicative of impaired mitochondrial function. Taken together, these findings provide new insights into potential mechanisms for hearing dysfunction in AD and suggest that DNA damage in the cochlea might contribute to the development of early hearing loss in AD.
{"title":"Early-Onset Hearing Loss in Mouse Models of Alzheimer's Disease and Increased DNA Damage in the Cochlea.","authors":"Jae-Hyeon Park, Burcin Duan Sahbaz, Komal Pekhale, Xixia Chu, Mustafa N Okur, Mhamed Grati, Kevin Isgrig, Wade Chien, Elena Chrysostomou, Lauren Sullivan, Deborah L Croteau, Uri Manor, Vilhelm A Bohr","doi":"10.59368/agingbio.20240025","DOIUrl":"10.59368/agingbio.20240025","url":null,"abstract":"<p><p>There is considerable interest in whether sensory deficiency is associated with the development of Alzheimer's disease (AD). Notably, the relationship between hearing impairment and AD is of high relevance but still poorly understood. In this study, we found early-onset hearing loss in two AD mouse models, 3xTgAD and 3xTgAD/Polβ<sup>+/-</sup>. The 3xTgAD/Polβ<sup>+/-</sup> mouse is DNA repair deficient and has more humanized AD features than the 3xTgAD. Both AD mouse models showed increased auditory brainstem response (ABR) thresholds between 16 and 32 kHz at 4 weeks of age, much earlier than any AD cognitive and behavioral changes. The ABR thresholds were significantly higher in 3xTgAD/Polβ<sup>+/-</sup> mice than in 3xTgAD mice at 16 kHz, and distortion product otoacoustic emission signals were reduced, indicating that DNA damage may be a factor underlying early hearing impairment in AD. Poly ADP-ribosylation and protein expression levels of DNA damage markers increased significantly in the cochlea of the AD mice but not in the adjacent auditory cortex. Phosphoglycerate mutase 2 levels and the number of synaptic ribbons in the presynaptic zones of inner hair cells were decreased in the cochlea of the AD mice. Furthermore, the activity of sirtuin 3 was downregulated in the cochlea of these mice, indicative of impaired mitochondrial function. Taken together, these findings provide new insights into potential mechanisms for hearing dysfunction in AD and suggest that DNA damage in the cochlea might contribute to the development of early hearing loss in AD.</p>","PeriodicalId":72130,"journal":{"name":"Aging Biology","volume":"1 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10948084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140159623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-15DOI: 10.59368/agingbio.20230018
Khachik K. Muradian, V. Fraifeld
{"title":"Embryogenesis of Longer-Lived Mammalian Species Occurs in a More Severe Hypoxic-Hypercapnic Environment","authors":"Khachik K. Muradian, V. Fraifeld","doi":"10.59368/agingbio.20230018","DOIUrl":"https://doi.org/10.59368/agingbio.20230018","url":null,"abstract":"","PeriodicalId":72130,"journal":{"name":"Aging Biology","volume":"78 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138999648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-20DOI: 10.59368/agingbio.20230016
Richard A Miller, Xinna Li, Gonzalo Garcia
{"title":"Erratum to “Aging Rate Indicators: Speedometers for Aging Research in Mice”","authors":"Richard A Miller, Xinna Li, Gonzalo Garcia","doi":"10.59368/agingbio.20230016","DOIUrl":"https://doi.org/10.59368/agingbio.20230016","url":null,"abstract":"","PeriodicalId":72130,"journal":{"name":"Aging Biology","volume":"18 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139257678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-04DOI: 10.59368/agingbio.20230012
M. Simons, Elizabeth D. Drake
{"title":"Stochasticity Explains Nongenetic Inheritance of Lifespan and Apparent Trade-Offs between Reproduction and Aging","authors":"M. Simons, Elizabeth D. Drake","doi":"10.59368/agingbio.20230012","DOIUrl":"https://doi.org/10.59368/agingbio.20230012","url":null,"abstract":"","PeriodicalId":72130,"journal":{"name":"Aging Biology","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88754960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-04DOI: 10.59368/agingbio.20230013
L. Fontana, V. Tosti, R. Barve, Beatrice Bertozzi, N. Veronese, F. Spelta, E. Cava, M. Mattson, L. Piccio, D. Early, R. Head
{"title":"When a Calorie Is Not a Calorie: Metabolic and Molecular Effects of Intermittent Fasting in Humans; Exploratory Outcomes of a Randomized Clinical Trial","authors":"L. Fontana, V. Tosti, R. Barve, Beatrice Bertozzi, N. Veronese, F. Spelta, E. Cava, M. Mattson, L. Piccio, D. Early, R. Head","doi":"10.59368/agingbio.20230013","DOIUrl":"https://doi.org/10.59368/agingbio.20230013","url":null,"abstract":"","PeriodicalId":72130,"journal":{"name":"Aging Biology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80545123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-30DOI: 10.59368/agingbio.20230009
S. Gonzalo, Rafael Cançado de Faria, E. Shashkova, Colin A. Flaveny, Á. Baldán, K. McCommis
{"title":"STAT1 Drives the Interferon-Like Response and Aging Hallmarks in Progeria","authors":"S. Gonzalo, Rafael Cançado de Faria, E. Shashkova, Colin A. Flaveny, Á. Baldán, K. McCommis","doi":"10.59368/agingbio.20230009","DOIUrl":"https://doi.org/10.59368/agingbio.20230009","url":null,"abstract":"","PeriodicalId":72130,"journal":{"name":"Aging Biology","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82864142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-29DOI: 10.59368/agingbio.20230004
V. Gorbunova
When a calorie is not a calorie: metabolic and molecular e ff ects of intermittent fasting in humans; exploratory outcomes of a randomized clinical trial. Tosti et al. Aging Biology Dietary restriction without malnutrition is the fi rst intervention found to extend lifespan in rodents and other organisms. Dietary restriction also has bene fi t in humans by reducing body weight, alleviating in fl ammation, and improving insulin sensitivity, among many other cardiometabolic and hormonal bene fi ts. However, continuous dietary restriction is di ffi cult for people to maintain. A more tolerable alternative to dietary restriction is intermittent fasting, where fasting happens every other day or on certain days of the week. Intermittent fasting extends lifespan and reduces in fl ammation in rodents, but whether it is equally bene fi cial in humans is unclear. A new study by Luigi Fontana, who is currently the scienti fi c director of the Charles Perkins Centre Royal Prince Alfred Clinic at The University of Sydney, shows that intermittent fasting is not as e ff ective in humans. In this randomized clinical trial that was conducted at Washington University in St. Louis where Fontana was a professor of medicine, overweight men and women were assigned to either intermittent fasting or Western-like diet for 6 months. In the second 6 months of the study, all participants underwent intermittent fasting. In the fasting group, participants were asked to eat non-starchy vegetable salads for lunch and dinner for two or three days a week. This novel “ vegetable fasting-mimicking ” approach helped to markedly improve compliance, and most of the participants completed the study, which is often not the case with more restrictive protocols. The study fi ndings were unexpected; although the intermittent fasting regiment induced an 8% weight loss and 16% reduction in total body fat, it did not alleviate in fl ammation and modestly improved insulin sensitivity. These fi ndings underscore that results from animal models cannot be easily extrapolated on humans. A day without food may provide a strong impact on a mouse with its fast metabolism, while having a milder e ff ect on a much larger human. More studies are needed to understand the impact of di ff erent degrees of dietary restriction on health in humans.
{"title":"How Much Should We Fast? A New Study by the Fontana Group Suggests That Intermittent Fasting May Be Too Mild for Humans","authors":"V. Gorbunova","doi":"10.59368/agingbio.20230004","DOIUrl":"https://doi.org/10.59368/agingbio.20230004","url":null,"abstract":"When a calorie is not a calorie: metabolic and molecular e ff ects of intermittent fasting in humans; exploratory outcomes of a randomized clinical trial. Tosti et al. Aging Biology Dietary restriction without malnutrition is the fi rst intervention found to extend lifespan in rodents and other organisms. Dietary restriction also has bene fi t in humans by reducing body weight, alleviating in fl ammation, and improving insulin sensitivity, among many other cardiometabolic and hormonal bene fi ts. However, continuous dietary restriction is di ffi cult for people to maintain. A more tolerable alternative to dietary restriction is intermittent fasting, where fasting happens every other day or on certain days of the week. Intermittent fasting extends lifespan and reduces in fl ammation in rodents, but whether it is equally bene fi cial in humans is unclear. A new study by Luigi Fontana, who is currently the scienti fi c director of the Charles Perkins Centre Royal Prince Alfred Clinic at The University of Sydney, shows that intermittent fasting is not as e ff ective in humans. In this randomized clinical trial that was conducted at Washington University in St. Louis where Fontana was a professor of medicine, overweight men and women were assigned to either intermittent fasting or Western-like diet for 6 months. In the second 6 months of the study, all participants underwent intermittent fasting. In the fasting group, participants were asked to eat non-starchy vegetable salads for lunch and dinner for two or three days a week. This novel “ vegetable fasting-mimicking ” approach helped to markedly improve compliance, and most of the participants completed the study, which is often not the case with more restrictive protocols. The study fi ndings were unexpected; although the intermittent fasting regiment induced an 8% weight loss and 16% reduction in total body fat, it did not alleviate in fl ammation and modestly improved insulin sensitivity. These fi ndings underscore that results from animal models cannot be easily extrapolated on humans. A day without food may provide a strong impact on a mouse with its fast metabolism, while having a milder e ff ect on a much larger human. More studies are needed to understand the impact of di ff erent degrees of dietary restriction on health in humans.","PeriodicalId":72130,"journal":{"name":"Aging Biology","volume":"102 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88328620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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