Pathobiology of aging & age related diseases最新文献

{"title":"Evaluation of aging, diabetes mellitus, and skin wounds by scanning acoustic microscopy with protease digestion.","authors":"Katsutoshi Miura,&nbsp;Kanna Yamashita","doi":"10.1080/20010001.2018.1516072","DOIUrl":"https://doi.org/10.1080/20010001.2018.1516072","url":null,"abstract":"<p><p>Scanning acoustic microscopy (SAM) can assess tissue stiffness by calculating the speed of sound (SOS) through tissues. SOS increases as tissue stiffness increases. Sensitivity to protease digestion depends on protein type, concentration, and modification. We analyzed the SOS images of formalin-fixed paraffin-embedded skin sections from elderly, young, diabetic, and nondiabetic subjects, as well as chronic and acute wounds. SAM provided high-resolution histology similar to LM and revealed characteristic SOS alteration following pepsin treatment. SOS values of dermis samples from elderly subjects (especially females) were lower than those of younger adults, which was indicative of age-related dermal softening and loosening. SOS values of elderly females were lower than those of younger females and elderly males. Dermal SOS showed a positive correlation with epidermal thickness. SOS values of epidermis of elderly subjects were higher than those of younger adults and showed a rapid decline 0.5h after protease digestion. Reticular dermis of diabetic patients exhibited greater pepsin resistance than that of nondiabetic patients. Chronic wounds exhibited greater SOS values and pepsin resistance than acute wounds. SOS variation with aging, diabetes mellitus, and wound fibrosis reflected histological and mechanical changes associated with senescence and disease duration. Epidermal thickness reflects age-related changes in dermal stiffness.</p>","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"8 1","pages":"1516072"},"PeriodicalIF":0.0,"publicationDate":"2018-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/20010001.2018.1516072","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36496160","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}

{"title":"Barshop Symposium on Aging 2017 Abstracts","authors":"W. Ladiges","doi":"10.1080/20010001.2018.1444939","DOIUrl":"https://doi.org/10.1080/20010001.2018.1444939","url":null,"abstract":"s from the meeting are presented in this issue, and represent a variety of aging and agerelated studies. A large focus was on aging and neurodegeneration including a number of presentations on Alzheimer’s disease. Other topics included cardiomyopathy, frailty, metabolism, pharmaceutical intervention of aging, age-related epigenetic modification, and cancer and aging. This annual meeting is well-attended and provides a seclusive and rustic environment in the Texas Hill Country for small group presentations and extensive informal interactions and discussions on the very latest findings and current thinking in the causes and prevention of aging and age-related diseases. LDLR-related protein 1 increases cytokine sensitivity. Implications for recovery after brain damage Sadiya Ahmad, Pamela Reed, Shane Sprague, Naomi L. Sayre University of Texas Health Science Center at San Antonio (UTHSCSA), TX Patients that express the Apolipoprotein E4 are predisposed to a poor long-term outcome after stroke. Explanations for this increased risk are not yet elucidated. This study aims to test one possible mechanism by which ApoE4 contributes to cognitive decline after stroke. Here, we examine the effect of a major ApoE4 receptor, low-density lipoprotein receptor related protein 1 (LRP1) on sensitivity to stress in astrocytes. LRP1 can promiscuously bind and move several extracellular ligands and plasma membrane proteins into the endocytic system. Notably, LRP1 was previously found to remove the TNF receptor (TNFR1) from the plasma membrane, although this has not been shown in astrocytes. We propose that a similar mechanism occurs in the central nervous system to attenuate inflammatory response after stroke. LRP1 binds and clears ApoE4 from the extracellular space via receptor-mediated endocytosis. However, previous studies have shown that the ApoE4, compared to other ApoE isoforms, slows the trafficking and recycling of endocytic LDL receptors. We propose that ApoE4 similarly inhibits LRP1 trafficking, and hypothesize that ApoE4 inhibits the ability of LRP1 to remove TNFR1 from the plasma membrane. This is expected to increase cytokine sensitivity, which would result in worse outcome after stroke and with aging. We investigated the effect of LRP1 on astrocyte TNFα signaling and response in immortalized ApoE null mouse astrocytes subjected to lentiviral-mediated knockdown ofLRP1. The astrocyte response to TNFα stimulation was tested in a concentration dependent manner using Western blotting of NFkB pathway components, which are the downstream mediators of TNFα signaling. We also tested astrocyte viability after prolonged TNFα stimulation using Alamar Blue reagent. We found that LRP1 deficient cells have increased phosphorylation of NFkB upon TNFα stimulation, and that loss of LRP1 resulted in significant loss of astrocyte viability after prolonged stimulation. Altogether, our results indicate that loss of LRP1 renders astrocytes more sensitive to TNFα. Future experi","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"177 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76724541","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}

{"title":"Exendin-4 protects mice from D-galactose-induced hepatic and pancreatic dysfunction.","authors":"Akram Ahangarpour,&nbsp;Ali Akbar Oroojan,&nbsp;Mohammad Badavi","doi":"10.1080/20010001.2017.1418593","DOIUrl":"https://doi.org/10.1080/20010001.2017.1418593","url":null,"abstract":"<p><p>Investigations into pharmaceutical intervention of pancreatic and hepatic dysfunction associated with metabolic disturbances have received relatively little attention. The aim of this study was to investigate the protective effects of exendin-4 in mice receiving D-galactose, a reducing sugar that triggers ROS production and inflammatory mediators affecting the pancreas and liver. Exendin-4 is an United States Food and Drug Administration (FDA) approved glucagon-like peptide that increases insulin dependent glycogen synthesis and glucose uptake. Male NMRI mice (20-25 g), 3 months of age, were randomly divided into 6 groups of 12 mice each: control, exendin-4 (1 nmol/kg), exendin-4 (10 nmol/kg), D-galactose, D-galactose + exendin-4 (1 nmol/kg) and D-galactose + exendin-4 (10 nmol/kg). D-galactose (500 mg/kg) was given daily by oral gavage for 6 weeks. During the last 10 days, exendin-4 (1 and 10 nmol/kg) was injected intraperitoneally daily. Glucose, insulin, insulin resistance, lipid profiles, and hepatic enzyme levels significantly increased in the D-galactose group (<i>p</i> < 0.05), along with a significant decrease in superoxide dismutase activity and pancreatic islet insulin secretion (<i>p</i> < 0.05). Exendin-4 decreased D-galactose-induced increases in serum glucose and insulin, insulin resistance, lipid profiles, and hepatic enzymes, and improved pancreatic islet insulin secretion and antioxidant defense status. The results show that exendin-4 can prevent complications in mice with compromised pancreatic and hepatic function. Long term administration of D-galactose in mice may be a useful model to study insulin resistance, metabolic syndrome, and aging.</p>","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"8 1","pages":"1418593"},"PeriodicalIF":0.0,"publicationDate":"2017-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/20010001.2017.1418593","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35726529","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}

{"title":"Testing drug combinations to slow aging.","authors":"Warren Ladiges,&nbsp;Denny Liggitt","doi":"10.1080/20010001.2017.1407203","DOIUrl":"https://doi.org/10.1080/20010001.2017.1407203","url":null,"abstract":"Aging is a complex multifactorial process, meaning that multiple pathways need to be targeted to effectively prevent or slow aging [1]. A number of molecular pathways are well known for influencing aging, but only a few have been successfully targeted with individual drugs, and these drugs do not individually target all aging pathways. However, combinations of these drugs might have the potential of effectively broadening the scope of aging targets. There are a number of drug combinations that could be combined based on different but overlapping pharmacological activities. Since the number one criterion for selecting drugs should be based on known anti-aging effects, for example, in preclinical mouse studies, the number of drugs available to consider is markedly reduced. Three drugs with well-validated anti-aging effects in laboratory animals, rapamycin [2,3], acarbose [4], and SS31 [5,6], are well suited to therapeutic multiplexing as a way to enhance healthy aging and stop the development of lesions associated with aging and physiological dysfunction based on interactive cellular mechanisms of each drug. The inter-drug relationship of these three drugs can easily be perceived by explicitly defining the mechanism of action of each drug and how it overlaps and extends the mechanism of action of each of the other drugs in the complex. A plausible explanation then of how they could act as a multiplex in targeting molecular pathways in aged mice is as follows:","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"8 1","pages":"1407203"},"PeriodicalIF":0.0,"publicationDate":"2017-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/20010001.2017.1407203","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35699685","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}

{"title":"The potential use of physical resilience to predict healthy aging.","authors":"Anna Schorr,&nbsp;Christy Carter,&nbsp;Warren Ladiges","doi":"10.1080/20010001.2017.1403844","DOIUrl":"https://doi.org/10.1080/20010001.2017.1403844","url":null,"abstract":"<p><p>Physical resilience is the ability of an organism to respond to stressors that acutely disrupt normal physiological homeostasis. By definition, resilience decreases with increasing age, while frailty, defined as a decline in tissue function, increases with increasing age. Assessment of resilience could therefore be an informative early paradigm to predict healthy aging compared to frailty, which measures late life dysfunction. Parameters for resilience in the laboratory mouse are not yet well defined, and no single standardized stress test exists. Since aging involves multiple genetic pathways, integrative responses involving multiple tissues, organs, and activities need to be measured to reveal the overall resilience status, suggesting a battery of stress tests, rather than a single all-encompassing one, would be most informative. Three simple, reliable, and inexpensive stressors are described in this review that could be used as a panel to determine levels of resilience. Brief cold water immersion allows a recovery time to normothermia as an indicator of resilience to hypothermia, i.e. the quicker the return to normal body temperature, the more robust the resilience. Sleep deprivation (SD) impairs remote memory in aged mice, and has detrimental effects on glucose metabolism. Cyclophosphamide (CYP) targets white blood cells, especially myeloid cells resulting in neutropenia with a rebound neutrophilia in an age-dependent manner. Thus a strong neutrophilic response indicates resilience. In conclusion, resilience promises to be an especially useful measurement of biological age, i.e. how fast a particular organ or tissue ages. The three stressors, cold, SD, and CYP, are applicable to human medicine and aging because they represent clinically relevant stress conditions that have effects in an age-dependent manner. They are thus an attractive perturbation for resilience testing in mice to measure the effectiveness of interventions that target basic aging processes.</p>","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"8 1","pages":"1403844"},"PeriodicalIF":0.0,"publicationDate":"2017-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/20010001.2017.1403844","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35699687","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}

{"title":"Effect of aging and lifestyle on photoreceptors and retinal pigment epithelium: cross-sectional study in a healthy Danish population.","authors":"Jacob Harris, Yousif Subhi, Torben L Sørensen","doi":"10.1080/20010001.2017.1398016","DOIUrl":"10.1080/20010001.2017.1398016","url":null,"abstract":"<p><p>Photoreceptors and their supporting retinal pigment epithelium constitute the key functional parts of the retina. Here, a study was undertaken to show how aging and lifestyle factors affect the photoreceptor layer and the retinal pigment epithelium and Bruch's membrane complex (RPE-BM) <i>in vivo</i> in a healthy Danish population using spectral-domain optical coherence tomography. This was a cross-sectional study of healthy humans aged ≥50 years. All participants were interviewed for medical history and lifestyle factors. Maculae of all participants were scanned using spectral-domain optical coherence tomography. The thickness of the photoreceptor layer and the RPE-BM was measured on one eye from each participant. In 150 eyes of 150 participants, it was found that aging was associated with a decrease in the thickness of the photoreceptor layer (-0.143 μm/year, P = 0.031) and an increase in the thickness of the RPE-BM layer (0.100 μm/year, P = 0.029) at the foveal minimum. Regarding lifestyle factors, alcohol intake or BMI were not associated with any significant trend, but physical inactivity and smoking had effects on the photoreceptor layer (decreased thickness) and the RPE-BM layer (increased thickness) indicating an accelerated aging process of the macula. Taken together, aging affects photoreceptors and the RPE-BM, and these aging trends are accelerated in smokers and the physically inactive.</p>","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"7 1","pages":"1398016"},"PeriodicalIF":0.0,"publicationDate":"2017-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5678353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35564884","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}

{"title":"Guidelines for collection and processing of lungs from aged mice for histological studies.","authors":"John Morton,&nbsp;Timothy A Snider","doi":"10.1080/20010001.2017.1313676","DOIUrl":"https://doi.org/10.1080/20010001.2017.1313676","url":null,"abstract":"<p><p>Pulmonary inflammation and the development of spontaneous lung tumors are important age-related lesions in mice. Therefore, gross and histological examination of the respiratory system is a critical component of geropathology research studies for translating surrogate endpoints to clinical aging studies. Collection, trimming, and processing of lung tissue from aged mice require a high-quality sequential process since aged mice are irreplaceable resource-intensive animal models. This protocol provides a basic technique that provides excellent sections for histological evaluation of the respiratory system of old mice suitable for most research applications. The points of emphasis are infusing the lungs at necropsy with formalin through the airways to prevent atelectasis artifacts that can preclude accurate histological evaluation, and embedding of anatomically oriented <i>in toto</i> lung lobes to allow for complete and thorough evaluation of all lung regions.</p>","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"7 1","pages":"1313676"},"PeriodicalIF":0.0,"publicationDate":"2017-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/20010001.2017.1313676","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35005330","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}

{"title":"Cardiotoxicity occurred in aged C57BL/6nia mice given a formulation containing poloxamer 407 hydrogel.","authors":"Terri Iwata,&nbsp;John Morton,&nbsp;Jessica Snyder,&nbsp;Xuan Ge","doi":"10.1080/20010001.2017.1304004","DOIUrl":"https://doi.org/10.1080/20010001.2017.1304004","url":null,"abstract":"Poloxamer 407 is a thermoreversible hydrogel frequently used as a carrier for polymer formulations in delayed-absorption drug studies, with limited toxicity in young mice. We gave six 24-month-old C57BL/6nia male mice each a subcutaneous injection of polylactic acid (PLA)/polyglycolic acid (PGA) copolymer biodegradable microparticles mixed with poloxamer 407 at a dose of 1.1 g/kg and 6 g/kg, respectively. Six days following injection, the animals presented as mild to moderately lethargic and dehydrated, and were subsequently killed. Histological evaluation revealed moderate to marked necrotizing myocarditis and myocardial hemorrhage (Figure 1). Two additional cohorts of similarly aged C57BL/6nia mice received the same PLA/PGA microparticle formulation but without poloxamer 407, and showed no adverse clinical signs or lesions of necrotizing myocarditis. These observations suggest that aged C57BL/6nia mice can be sensitive to the cardiotoxic effects of poloxamer 407 under certain dose conditions.","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"7 1","pages":"1304004"},"PeriodicalIF":0.0,"publicationDate":"2017-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/20010001.2017.1304004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35005328","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}

{"title":"The emerging role of geropathology in preclinical aging studies.","authors":"Warren Ladiges","doi":"10.1080/20010001.2017.1304005","DOIUrl":"https://doi.org/10.1080/20010001.2017.1304005","url":null,"abstract":"In 2015, the United States National Institute on Aging funded the Geropathology Initiative, designed to develop a systematic approach for using the pathology of aging as a way to assess anti-aging interventions. As a result, the Geropathology Research Network was formed, consisting of various working groups composed of experts in anatomic pathology, molecular pathology, and translational geroscience. Within the Anatomic Pathology Working Group, a Geropathology Grading Committee was formed for the purpose of developing guidelines for a scoring system based on the increasing severity of lesions associated with increasing age, using the mouse as the preclinical prototype model. The committee consists of a chair, Warren Ladiges, DVM, MSc, a program coordinator, John Morton, BS, from the Department of Comparative Medicine, University of Washington, Seattle, WA, and six boardcertified veterinary pathologists: Denny Liggitt, DVM, PhD and Jessica Snyder, DVM, PhD, from the Department of Comparative Medicine, University of Washington, Seattle, WA, Tim Snider, DVM, PhD, from the Department of Veterinary Pathology, Oklahoma State University, Stillwater, OK, Erby Wilkinson, DVM, PhD, from the Department of Pathology, University of Michigan, Ann Arbor, MI, Denise Imai, DVM, PhD, from the Department of Comparative Pathology, University of California, Davis, Davis, CA, and Smitha Pillai, DVM, PhD, from the Fred Hutchinson Cancer Research Center, Seattle, WA. This committee has been actively engaged in teleconferences, meetings, and workshops to develop the Geropathology Grading Platform (GGP). The GGP is based on a standard set of guidelines designed to (1) detect the histological presence or absence of lowimpact lesions; and (2) determine the level of severity of high-impact lesions in organs from aged mice [1]. The platform is designed to generate a numerical score for each lesion in a specific organ, so that a total lesion score is obtained by adding each lesion score for that organ for one mouse. Total lesion scores are averaged between all mice in a specific cohort to obtain a composite lesion score (CLS) for that organ. The CLS can then be used to compare responses to drug treatment over time, determine the effect of alterations in gene expression, or investigate the impact of environmental challenges in a variety of preclinical aging studies [2]. This platform has been used to compare CLS in two different mouse strains at increasing ages, showing that CLSs increase similarly in both strains with increasing age but at different rates in different organs [3]. The platform also showed that middle-aged mice treated with the anti-aging drug rapamycin for 2 months had lower CLSs than mice treated with placebo. CLSs correlate well with other measures of aging, such as chronic progressive heart disease defined by an increasing left ventricular mass index [3], and an age-dependent increase in carpal joint lesions in association with a decrease in grip strength of","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"7 1","pages":"1304005"},"PeriodicalIF":0.0,"publicationDate":"2017-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/20010001.2017.1304005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35005329","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}

{"title":"Neurochemical and motor changes in mice with combined mutations linked to Parkinson's disease.","authors":"Xiang Bai, Margaret Chia-Ying Wey, Paul Anthony Martinez, Chao Shi, Elizabeth Fernandez, Randy Strong","doi":"10.1080/20010001.2017.1267855","DOIUrl":"10.1080/20010001.2017.1267855","url":null,"abstract":"<p><p>Considerable evidence suggests that oxidative stress plays a role in the pathogenesis of Parkinson's disease (PD), the most prevalent neurodegenerative movement disorder. Reduced expression of aldehyde dehydrogenase-1 (ALDH1) and glutathione peroxidase-1 (GPX1), enzymes that function to detoxify aldehydes and hydroxyl radicals, respectively, has been reported in the substantia nigra of patients who died with PD. To determine whether deficiency in these two genes contributes to the pathogenesis of PD, mice were generated with homozygous null mutations of both Aldh1a1 (the murine homolog of ALDH1) and Gpx1 genes [knockout (KO) mice]. At 6 and 18 months of age, KO mice showed a significantly decreased latency to fall in the automated accelerating rotarod test and increased time to complete the pole test opamine levels were not altered; however, the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) and the DOPAC/dopamine ratio were significantly reduced at 18 months of age. Proteins adducted with 4-hydroxynonenal, the end-product of lipid peroxidation, were increased in the. midbrain and striatum of KO mice at 6 and 18 months. In conclusion, dual mutations in Gpx1 and Aldh1a1 genes are associated with motor deficits and increased lipid peroxidation in adult mice.</p>","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"7 1","pages":"1267855"},"PeriodicalIF":0.0,"publicationDate":"2017-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5328310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34840934","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}