path(MESH:Aging)

Entity

Name

Aging

Namespace

MeSH

Namespace Version

20181007

Namespace URL

https://raw.githubusercontent.com/pharmacome/terminology/01c9daa61012b37dd0a1bc962521ba51a15b38f1/external/mesh-names.belns

However, loss of brain nAChRs precedes that of muscarinic receptors during normal aging, and it is often much more extensive in human brains afflicted with AD relative to age-matched controls (236, 308, 373, 374, 416, 519). In fact, alpha4 nAChR expression can decrease by >80% in the AD brain (306, 374). PubMed:19126755

As will be returned to below, it is also the first nAChR subtype to exhibit measurable decline in expression in the aged mammalian brain and especially in neurodegenerative disorders such as AD (236, 374). PubMed:19126755

Mouse strains, like humans, also exhibit a striking age-related decline in nAChR expression. For instance, in the hippocampus of aged CBA and B6 mice, expression of alpha4 and alpha7 nAChR subunits decreases with age (166). PubMed:19126755

Mouse strains, like humans, also exhibit a striking age-related decline in nAChR expression. For instance, in the hippocampus of aged CBA and B6 mice, expression of alpha4 and alpha7 nAChR subunits decreases with age (166). PubMed:19126755

These findings are in line with evidence suggesting that increased oxi- dative stress157 and loss of vascular integrity contribute to ageing158 and AD,159 as demonstrated by accelerated breakdown of the BBB and the neurovascular unit. PubMed:26195256

Various factors have been reported to positively and negatively modulate the risk of LOAD. Specifically, the greatest overall risk factor for LOAD is ageing; PubMed:26195256

Genes downregulated with aging and upregulated by FKBP1b (AC downregulated vs YC, FKBP1b upregulated vs AC, template II) strongly overrepresented GO categories related to intracellular and extracellular structure, including: cytoskeleton, extracellular region passive transmembrane transporter activity, ectoderm devel- opment, regulation of actin cytoskeleton organization, and regulation of MAP kinase activity (Table 1) PubMed:29255009

Genes downregulated with aging and upregulated by FKBP1b (AC downregulated vs YC, FKBP1b upregulated vs AC, template II) strongly overrepresented GO categories related to intracellular and extracellular structure, including: cytoskeleton, extracellular region passive transmembrane transporter activity, ectoderm devel- opment, regulation of actin cytoskeleton organization, and regulation of MAP kinase activity (Table 1) PubMed:29255009

Genes downregulated with aging and upregulated by FKBP1b (AC downregulated vs YC, FKBP1b upregulated vs AC, template II) strongly overrepresented GO categories related to intracellular and extracellular structure, including: cytoskeleton, extracellular region passive transmembrane transporter activity, ectoderm devel- opment, regulation of actin cytoskeleton organization, and regulation of MAP kinase activity (Table 1) PubMed:29255009

Genes downregulated with aging and upregulated by FKBP1b (AC downregulated vs YC, FKBP1b upregulated vs AC, template II) strongly overrepresented GO categories related to intracellular and extracellular structure, including: cytoskeleton, extracellular region passive transmembrane transporter activity, ectoderm devel- opment, regulation of actin cytoskeleton organization, and regulation of MAP kinase activity (Table 1) PubMed:29255009

Genes upregulated with aging and downregulated by FKBP1b (AC upregulated vs YC, FKBP1b downregulated vs AC, template IV) overrepresented GO category annotations related to extracel- lular remodeling and transporter activity, including extracellular matrix, primary transmembrane transporter activity, blood vessel development, regulation of cell motion, and membrane-bounded vesicle (Table 1) PubMed:29255009

Genes upregulated with aging and downregulated by FKBP1b (AC upregulated vs YC, FKBP1b downregulated vs AC, template IV) overrepresented GO category annotations related to extracel- lular remodeling and transporter activity, including extracellular matrix, primary transmembrane transporter activity, blood vessel development, regulation of cell motion, and membrane-bounded vesicle (Table 1) PubMed:29255009

Genes upregulated with aging and downregulated by FKBP1b (AC upregulated vs YC, FKBP1b downregulated vs AC, template IV) overrepresented GO category annotations related to extracel- lular remodeling and transporter activity, including extracellular matrix, primary transmembrane transporter activity, blood vessel development, regulation of cell motion, and membrane-bounded vesicle (Table 1) PubMed:29255009

Genes upregulated with aging and downregulated by FKBP1b (AC upregulated vs YC, FKBP1b downregulated vs AC, template IV) overrepresented GO category annotations related to extracel- lular remodeling and transporter activity, including extracellular matrix, primary transmembrane transporter activity, blood vessel development, regulation of cell motion, and membrane-bounded vesicle (Table 1) PubMed:29255009

Twenty-four mTOR pathway genes were identified by searching the GO data- base and the literature (Johnson et al., 2013). Of these 24, only two, Hif1an and Nfkb1, were significantly altered with both age (upregulated) and FKBP1b (downregulated), showing that the mTOR pathway was not statistically overrepresented by FKBP1b- sensitive genes (n.s., p 􏰆 0.78, binomial test). PubMed:29255009

Twenty-four mTOR pathway genes were identified by searching the GO data- base and the literature (Johnson et al., 2013). Of these 24, only two, Hif1an and Nfkb1, were significantly altered with both age (upregulated) and FKBP1b (downregulated), showing that the mTOR pathway was not statistically overrepresented by FKBP1b- sensitive genes (n.s., p 􏰆 0.78, binomial test). PubMed:29255009

As will be returned to below, it is also the first nAChR subtype to exhibit measurable decline in expression in the aged mammalian brain and especially in neurodegenerative disorders such as AD (236, 374). PubMed:19126755

However, loss of brain nAChRs precedes that of muscarinic receptors during normal aging, and it is often much more extensive in human brains afflicted with AD relative to age-matched controls (236, 308, 373, 374, 416, 519). In fact, alpha4 nAChR expression can decrease by >80% in the AD brain (306, 374). PubMed:19126755

First, age-related nAChR subunit expression decline was observed in both strains, and this was dominated by diminished alpha4 nAChR expression. Second, long-term (12 mo) oral nicotine failed to reduce the age-related decline in the number of neurons expressing alpha4 nAChR subunits, although the neurons that remained exhibited larger processes with more varicosities than age-matched controls (165, 396). Acute nicotine treatment (alpha6 wk of oral nicotine) of aged mice had no measurable influence on nAChR expression, neuronal viability, or dendritic complexity (e.g., Ref. 396) PubMed:19126755

First, age-related nAChR subunit expression decline was observed in both strains, and this was dominated by diminished alpha4 nAChR expression. Second, long-term (12 mo) oral nicotine failed to reduce the age-related decline in the number of neurons expressing alpha4 nAChR subunits, although the neurons that remained exhibited larger processes with more varicosities than age-matched controls (165, 396). Acute nicotine treatment (alpha6 wk of oral nicotine) of aged mice had no measurable influence on nAChR expression, neuronal viability, or dendritic complexity (e.g., Ref. 396) PubMed:19126755

Mouse strains, like humans, also exhibit a striking age-related decline in nAChR expression. For instance, in the hippocampus of aged CBA and B6 mice, expression of alpha4 and alpha7 nAChR subunits decreases with age (166). PubMed:19126755

Mouse strains, like humans, also exhibit a striking age-related decline in nAChR expression. For instance, in the hippocampus of aged CBA and B6 mice, expression of alpha4 and alpha7 nAChR subunits decreases with age (166). PubMed:19126755

Various factors have been reported to positively and negatively modulate the risk of LOAD. Specifically, the greatest overall risk factor for LOAD is ageing; PubMed:26195256

First, in ageing, and particularly in AD, CSF production by the choroid plexus is reduced, as shown by decreased water secretion into the ventricles via AQP1 water channels. PubMed:26195256