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Older-aged C57BL/6 mice fed a diet high in saturated fat and sucrose for ten months show decreased resilience to aging 老年C57BL/6小鼠连续10个月高饱和脂肪和高蔗糖饮食后，抗衰老能力下降
Aging pathobiology and therapeutics Pub Date : 2023-09-20 DOI: 10.31491/apt.2023.09.120
Chloe Johnson, Lida Zhu, Ruby Mangalindan, Jeremy Whitson, Maryia Sweetwyne, Ana P. Valencia, David J. Marcinekd, Peter Rabinovitch, Warren Ladiges
{"title":"Older-aged C57BL/6 mice fed a diet high in saturated fat and sucrose for ten months show decreased resilience to aging","authors":"Chloe Johnson, Lida Zhu, Ruby Mangalindan, Jeremy Whitson, Maryia Sweetwyne, Ana P. Valencia, David J. Marcinekd, Peter Rabinovitch, Warren Ladiges","doi":"10.31491/apt.2023.09.120","DOIUrl":"https://doi.org/10.31491/apt.2023.09.120","url":null,"abstract":"The ability to respond to physical stress that disrupts normal physiological homeostasis at an older age embraces the concept of resilience to aging. A physical stressor could be used to induce physiological responses that are age-related, since resilience declines with increasing age. Increased fat and sugar intake is a nutritional stress with a high prevalence of obesity in older people. In order to determine the effect of this type of diet on resilience to aging, 18-month-old C57BL/6J male mice were fed a diet high in saturated fat (lard) and sucrose (HFS) for ten months. At the end of the 10-month study, mice fed the HFS diet showed increased cognitive impairment, decreased cardiac function, decreased strength and agility, and increased severity of renal pathology compared to mice fed a rodent chow diet low in saturated fat and sucrose (LFS). The degree of response aligned with decreased resilience to the long-term adverse effects of the diet with characteristics of accelerated aging. This observation suggests additional studies could be conducted to investigate the relationship between an accelerated decline in resilience to aging and enhanced resilience to aging under different dietary conditions.","PeriodicalId":7500,"journal":{"name":"Aging pathobiology and therapeutics","volume":"72 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136378415","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}
引用次数: 0
The role of immune aging in Giant Cell Arteritis 免疫老化在巨细胞动脉炎中的作用
Aging pathobiology and therapeutics Pub Date : 2023-09-20 DOI: 10.31491/apt.2023.09.119
Patricia Harkins, Sharon Cowley, Robert Harrington, David Kane, Richard Conway
{"title":"The role of immune aging in Giant Cell Arteritis","authors":"Patricia Harkins, Sharon Cowley, Robert Harrington, David Kane, Richard Conway","doi":"10.31491/apt.2023.09.119","DOIUrl":"https://doi.org/10.31491/apt.2023.09.119","url":null,"abstract":"Giant cell arteritis (GCA) is a granulomatous vasculitis with a predilection for medium and large calibre arteries. The most significant risk factor for its development is advancing age, with a peak incidence in the seventh and eighth decades of life. Despite this, until recently, the role of aging in disease pathogenesis has been largely overlooked. Advancing age is associated with numerous alterations in both the innate and adaptive immune system. Indeed, there is significant overlap in the cellular and molecular pathways involved in immune aging and those observed in the pathogenesis of GCA. In this review we explore these similarities and further expand the discussion on the postulated role of accelerated immune ageing in the pathogenesis of GCA. With the dramatic increase in lifespan in recent decades, elucidating the potential role of early immune aging in disease pathogenesis is extremely pertinent, with the potential to offer a new therapeutic avenue not only for those with GCA, but all immune mediated rheumatic diseases.","PeriodicalId":7500,"journal":{"name":"Aging pathobiology and therapeutics","volume":"91 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136378416","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}
引用次数: 0
Physical resilience is a predictor of healthy aging 身体恢复力是健康衰老的一个预测指标
Aging pathobiology and therapeutics Pub Date : 2023-09-20 DOI: 10.31491/apt.2023.09.117
Warren Ladiges
{"title":"Physical resilience is a predictor of healthy aging","authors":"Warren Ladiges","doi":"10.31491/apt.2023.09.117","DOIUrl":"https://doi.org/10.31491/apt.2023.09.117","url":null,"abstract":"Physical resilience is defined as the ability to respond to and recover from a physically stressful event. Response to stress can be heterogeneous across lifespan and between individuals of the same age. Documentation of resilience at a young age would provide insight into how individuals across lifespan would develop resilience to physical stress at an older age and help identify individuals determined to be less resilient. Protective factors could be developed that can be engaged to promote resilience and healthy aging and provide insight as to why some individuals maintain or regain function following an insult while others do not. Preclinical animal studies will provide valuable information as to the molecular pathways involved in individual heterogeneity and help identify therapeutic targets. The concept that resilience to aging is characterized by heterogeneous response patterns unique to specific physical stressors is an excellent translational platform for determining the optimal age, scope, and intensity of physical stressors to reliably discriminate resilience.","PeriodicalId":7500,"journal":{"name":"Aging pathobiology and therapeutics","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136378413","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}
引用次数: 0
Biobased nanoemulsions for targeted drug delivery to treat dementia and aging 用于治疗痴呆和衰老的靶向药物递送的生物基纳米乳液
Aging pathobiology and therapeutics Pub Date : 2023-09-20 DOI: 10.31491/apt.2023.09.121
Joseph S. D'Arrigo
{"title":"Biobased nanoemulsions for targeted drug delivery to treat dementia and aging","authors":"Joseph S. D'Arrigo","doi":"10.31491/apt.2023.09.121","DOIUrl":"https://doi.org/10.31491/apt.2023.09.121","url":null,"abstract":"Early changes in cerebrovascular hemodynamics and endothelial function can contribute to altered cognitive function and systemic vascular stiffness later in life. Accordingly, vascular pathology accompanies the mechanisms underlying aging. The development of chronic cerebral hypoperfusion, which leads to a lack of blood flow to the brain, is a common trait despite the various and complex pathogenic mechanisms causing these vascular alterations. Drugs or other bioactive compounds can be incorporated into a \"high density lipoprotein-like\" (\"HDL-like\") lipid nanocarrier to create a multifunctional \"combination therapeutic\" that can target cell-surface scavenger receptors, primarily class B type I (i.e., SR-BI). The enhanced endocytosis of the nanocarrier's drug contents into various target cells, made possible by this proposed (biomimetic-nanocarrier) therapeutic vehicle, increases the likelihood that this multitasking \"combination therapeutic\" will be more effective at various stages of dementia.","PeriodicalId":7500,"journal":{"name":"Aging pathobiology and therapeutics","volume":"6 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136378414","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}
引用次数: 0
Cardiovascular aging in patients with chronic kidney disease: pathogenesis and potential therapeutics 慢性肾病患者的心血管老化:发病机制和潜在的治疗方法
Aging pathobiology and therapeutics Pub Date : 2023-09-20 DOI: 10.31491/apt.2023.09.118
Safa Alkhayyat, Zahraa Alhoori, Mohamed Abdalbary
{"title":"Cardiovascular aging in patients with chronic kidney disease: pathogenesis and potential therapeutics","authors":"Safa Alkhayyat, Zahraa Alhoori, Mohamed Abdalbary","doi":"10.31491/apt.2023.09.118","DOIUrl":"https://doi.org/10.31491/apt.2023.09.118","url":null,"abstract":"Patients with chronic kidney dysfunction have an elevated risk for various cardiovascular diseases. Even in the early stages of chronic kidney disease (CKD) the prevalence of cardiovascular events and mortalities is extremely high if compared with age-matched general population. With worsening of kidney function this risk is growing intensely. There are many traditional and non-traditional risk factors that can lead to cardiovascular disease in CKD. Cardiovascular rather than kidney failure, per se, is the main cause of mortality in CKD. The increase of calcification promoters and the decrease of inhibitors leads to the development of vascular calcification in the early stages of CKD. In this regard, CKD mimics cardiovascular system aging with a premature onset and an accelerated progression.Various non-pharmacological and pharmacological interventions have been studied to retard premature cardiovascular aging in CKD. In this review article, we are summarizing the pathogenesis, risk factors, and possible management strategies of cardiovascular disease in CKD.","PeriodicalId":7500,"journal":{"name":"Aging pathobiology and therapeutics","volume":"76 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136378417","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}
引用次数: 0
GHK peptide prevents sleep-deprived learning impairment in aging mice. GHK肽可防止老龄小鼠在睡眠不足的情况下出现学习障碍。
Aging pathobiology and therapeutics Pub Date : 2023-01-01 Epub Date: 2023-03-29 DOI: 10.31491/apt.2023.03.109
Manuela Rosenfeld, Katie Nickel, Warren Ladiges
{"title":"GHK peptide prevents sleep-deprived learning impairment in aging mice.","authors":"Manuela Rosenfeld, Katie Nickel, Warren Ladiges","doi":"10.31491/apt.2023.03.109","DOIUrl":"10.31491/apt.2023.03.109","url":null,"abstract":"<p><p>Sleep deprivation is known to cause memory impairment and is associated with inflammation and cell damage linked to neurodegenerative diseases. GHK (glycyl-L-histidyl-L-lysine) is a naturally occurring tripeptide found in mammalian plasma. GHK has anti-inflammatory activity and can pass through the blood-brain barrier suggesting the potential to prevent neuroinflammation associated with sleep deprivation. In this study, mice were injected with 15 mg/kg GHK per day for five days and sleep deprived on the last two days of treatment. Sleep-deprived mice treated with GHK did not show the acute learning impairment seen in sleep-deprived mice treated with saline. GHK prevented an increase in MCP-1 and nitrotyrosine levels in the hippocampus of sleep-deprived mice suggesting that inflammatory and reactive nitrogen/oxygen species activity could be therapeutic targets for learning impairment associated with short-term sleep deprivation.</p>","PeriodicalId":7500,"journal":{"name":"Aging pathobiology and therapeutics","volume":"5 1","pages":"33-35"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10081520/pdf/nihms-1887245.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9651969","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}
引用次数: 0
The CB6F1 mouse is a model for studying cognition and brain morphometry with increasing age. CB6F1 小鼠是研究认知和大脑形态随年龄增长而变化的模型。
Aging pathobiology and therapeutics Pub Date : 2023-01-01 Epub Date: 2023-03-29 DOI: 10.31491/apt.2023.03.110
Devika Gandhay, Christina Pettan-Brewer, Warren Ladiges
{"title":"The CB6F1 mouse is a model for studying cognition and brain morphometry with increasing age.","authors":"Devika Gandhay, Christina Pettan-Brewer, Warren Ladiges","doi":"10.31491/apt.2023.03.110","DOIUrl":"10.31491/apt.2023.03.110","url":null,"abstract":"<p><p>Cognitive impairment associated with memory loss and dysfunctional communication is a common condition in older people. Regions of the brain have been reported to decrease in size with increasing age, but the relationship with cognitive impairment is not well understood. Inbred and hybrid mouse strains can be useful models to investigate cognitive impairment and morphological changes at older ages. CB6F1 hybrid mice, a cross between C57BL/6 and Balb/c mice, were tested for learning and memory using a radial water tread maze. Old CB6F1 male mice (30 months of age) had severe cognitive impairment, while it was virtually absent in young (6 months old) male mice. In these same mice, there was a significant decrease in sagittal flat surface area of the hippocampus and pons in old versus young animals. The aging CB6F1 mouse would be a potential model to study the relationship between changes in brain morphometry and cognitive impairment and the identification of possible therapeutic targets.</p>","PeriodicalId":7500,"journal":{"name":"Aging pathobiology and therapeutics","volume":"5 1","pages":"36-38"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10327541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9801588","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}
引用次数: 0
Sex Matters in Aging. The Canagliflozin Story. 性与衰老有关。卡格列净的故事。
Aging pathobiology and therapeutics Pub Date : 2022-01-01 DOI: 10.31491/apt.2022.09.091
Jackson Wezeman, Warren Ladiges
{"title":"Sex Matters in Aging. The Canagliflozin Story.","authors":"Jackson Wezeman,&nbsp;Warren Ladiges","doi":"10.31491/apt.2022.09.091","DOIUrl":"https://doi.org/10.31491/apt.2022.09.091","url":null,"abstract":"<p><p>A promising and novel approach for identifying anti-aging therapeutics has been the repurposing of clinically approved and readily available drugs in mice. Canagliflozin, a clinically approved safe, and effective drug for type 2 diabetic patients, was recently shown to robustly retard age-related lesions in male mice but less so in female mice. While this type of sex disparity is often seen in the field of aging, it does represent a dilemma of not knowing the cause or how translationally relevant the sex differences would be in older humans treated with Canagliflozin. Thoughtful and mechanistic investigations are needed to understand why these differences are present and whether they can be eliminated by new drugs or drug combinations. Success in using repurposed drugs for aging intervention studies in humans will depend on preclinical research to uncover pathways that can be targeted for the benefit of both sexes.</p>","PeriodicalId":7500,"journal":{"name":"Aging pathobiology and therapeutics","volume":"4 3","pages":"84-86"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9762679/pdf/nihms-1839909.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10414525","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}
引用次数: 0
A mouse model of naturally occurring age-related cognitive impairment. 自然发生的老年性认知障碍的小鼠模型。
Aging pathobiology and therapeutics Pub Date : 2022-01-01 Epub Date: 2022-09-30 DOI: 10.31491/apt.2022.09.090
Sara Daneshjoo, Joo Young Park, Juliana Moreno, Manuela Rosenfeld, Martin Darvas, Warren Ladiges
{"title":"A mouse model of naturally occurring age-related cognitive impairment.","authors":"Sara Daneshjoo, Joo Young Park, Juliana Moreno, Manuela Rosenfeld, Martin Darvas, Warren Ladiges","doi":"10.31491/apt.2022.09.090","DOIUrl":"10.31491/apt.2022.09.090","url":null,"abstract":"<p><p>Age-related cognitive impairment (ARCI) is a neurological condition that affects millions of older people, but little is known about the increased risk of developing more severe neurodegeneration and dementia. Preclinical research is needed to understand the mechanisms of the impairment and the neuropathology associated with it. We have characterized a model of naturally occurring ARCI in the C57BL/6J mouse strain that shows an age-dependent development of cognitive impairment. As in people, some mice have little cognitive impairment while others have more severe cognitive impairment. Therefore, mice can be categorized as resistant or susceptible and the two groups can be studied for behavioral and neuropathology differences. Preliminary observations show no difference in strength and agility test scores between ARCI resistant and susceptible mice of either sex suggesting the cognitive impairment in ARCI susceptible mice is not accompanied by impairment in daily living activities, similar to ARCI in humans. The hippocampal area of the brain from ARCI susceptible mice shows evidence of an increase in the inflammatory cytokine MCP-1 compared to ARCI resistant mice, suggesting inflammation may be associated with ARCI. These preliminary observations suggest that ARCI in C57BL/6J mice could be a high-impact model to study how resilience to brain aging may predict resilience to dementia associated with Alzheimer's disease and other age-related neurological conditions.</p>","PeriodicalId":7500,"journal":{"name":"Aging pathobiology and therapeutics","volume":" ","pages":"87-89"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9562129/pdf/nihms-1839903.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33545824","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}
引用次数: 0
Long-term treatment with Elamipretide enhances healthy aging phenotypes in mice. 长期服用依来美肽可增强小鼠的健康老化表型。
Aging pathobiology and therapeutics Pub Date : 2022-01-01 Epub Date: 2022-09-30 DOI: 10.31491/apt.2022.09.089
Katie Nickel, Lida Zhu, Ruby Mangalindan, Jessica M Snyder, Matthew Tucker, Jeremy Whitson, Maryia Sweetwyne, Ana P Valencia, Jenna Klug, Zhou Jiang, David J Marcinek, Peter Rabinovitch, Warren Ladiges
{"title":"Long-term treatment with Elamipretide enhances healthy aging phenotypes in mice.","authors":"Katie Nickel, Lida Zhu, Ruby Mangalindan, Jessica M Snyder, Matthew Tucker, Jeremy Whitson, Maryia Sweetwyne, Ana P Valencia, Jenna Klug, Zhou Jiang, David J Marcinek, Peter Rabinovitch, Warren Ladiges","doi":"10.31491/apt.2022.09.089","DOIUrl":"10.31491/apt.2022.09.089","url":null,"abstract":"<p><strong>Background: </strong>Disruption of metabolic and bioenergetic homeostasis related to mitochondrial dysfunction is a key driver of aging biology. Therefore, targeting mitochondrial function would be a rational approach to slowing aging. Elamipretide (Elam, a.k.a. SS-31) is a peptide known to target mitochondria and suppress mammalian signs of aging. The present study was designed to examine the phenotypic effects of long-term Elam treatment on aging in C57BL/6 mice starting at 18 months of age.</p><p><strong>Methods: </strong>Mice were fed regular chow (RC diet) or a diet high in fat and sugar (HF diet) and treated with 3 mg/kg of Elam or saline subcutaneously 5 days per week for 10 months. Physiological performance assessments were conducted at 28 months of age.</p><p><strong>Results: </strong>Elam improved the physical performance of males but not females, while in females Elam improved cognitive performance and enhanced the maintenance of body weight and fat mass. It also improved diastolic function in both males and females, but to a greater extent in males. The HF diet over 10 months had a negative effect on health span, as it increased body fat and decreased muscle strength and heart function, especially in females.</p><p><strong>Conclusions: </strong>Elam enhanced healthy aging and cardiac function in both male and female mice, although the specific effects on function differed between sexes. In females, the treatment led to better cognitive performance and maintenance of body composition, while in males, performance on a rotating rod was preserved. These overall observations have translational implications for considering additional studies using Elam in therapeutic or preventive approaches for aging and age-related diseases.</p>","PeriodicalId":7500,"journal":{"name":"Aging pathobiology and therapeutics","volume":"4 3","pages":"76-83"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9562127/pdf/nihms-1839907.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9267641","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}
引用次数: 0
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