bp(GO:aging)
The reported findings that ageing is also associated with peripheral lymphatic dysfunction led us to hypothesize that the deterioration of meningeal lymphatic vessels underlies some aspects of age-associated cognitive decline PubMed:30046111
Enrichment analysis revealed, however, changes in gene sets involved in immune and inflammatory responses, phospholipid metabolism, extracellular matrix organization, cellular adhesion and endothelial tube morphogenesis, all of which suggest that there are functional alterations in meningeal LECs with age (Fig. 2c). PubMed:30046111
Enrichment analysis revealed, however, changes in gene sets involved in immune and inflammatory responses, phospholipid metabolism, extracellular matrix organization, cellular adhesion and endothelial tube morphogenesis, all of which suggest that there are functional alterations in meningeal LECs with age (Fig. 2c). PubMed:30046111
Enrichment analysis revealed, however, changes in gene sets involved in immune and inflammatory responses, phospholipid metabolism, extracellular matrix organization, cellular adhesion and endothelial tube morphogenesis, all of which suggest that there are functional alterations in meningeal LECs with age (Fig. 2c). PubMed:30046111
Enrichment analysis revealed, however, changes in gene sets involved in immune and inflammatory responses, phospholipid metabolism, extracellular matrix organization, cellular adhesion and endothelial tube morphogenesis, all of which suggest that there are functional alterations in meningeal LECs with age (Fig. 2c). PubMed:30046111
Enrichment analysis revealed, however, changes in gene sets involved in immune and inflammatory responses, phospholipid metabolism, extracellular matrix organization, cellular adhesion and endothelial tube morphogenesis, all of which suggest that there are functional alterations in meningeal LECs with age (Fig. 2c). PubMed:30046111
Enrichment analysis revealed, however, changes in gene sets involved in immune and inflammatory responses, phospholipid metabolism, extracellular matrix organization, cellular adhesion and endothelial tube morphogenesis, all of which suggest that there are functional alterations in meningeal LECs with age (Fig. 2c). PubMed:30046111
Dementia is a debilitating condition frequent in ageing populations, and Alzheimer's Disease (AD) accounts for 70% of all dementia cases. AD is characterized by neuropathological hallmarks consisting of an accumulation of Amyloid beta peptide (Ab) in extracellular plaques, intracellular deposits of tau protein, neuronal loss and, more recently, a prominent synaptic loss was identified (Braak and Braak,1991; Masliah et al., 2001; Selkoe,1991; Spires-Jones and Hyman, 2014) PubMed:25514383
However, we identify a possible role of the alpha7 subunit in the normal aging process that should be further investigated PubMed:27522251
The levels of alpha4 and alpha7 nAChR mRNA showed a decrease with aging, whereas the levels of alpha3 mRNA were unchanged in the elderly brain relative to the fetal brain (Hellstro¨m-Lindahl et al 1998) PubMed:11230871
The levels of alpha4 and alpha7 nAChR mRNA showed a decrease with aging, whereas the levels of alpha3 mRNA were unchanged in the elderly brain relative to the fetal brain (Hellstro¨m-Lindahl et al 1998) PubMed:11230871
A significant decrease in [3H]epibatidine binding has been observed with aging in the human cortical brain regions and cerebellum (Marutle et al 1998) PubMed:11230871
In addition, a marked reduction in the laminar distribution of [3H]epibatidine binding was observed in control cortical tissue with aging (Figure 1) PubMed:11230871
Lindquist and colleagues proposed that inhibition of UPS, which can be caused by ageing or following a pharmacological treatment, can lead to accumulation of PrPc in the cytoplasm where it is spontaneously converted into a PrPsc-like species because it is not rapidly degraded by the UPS (Hooper, 2003; Ma and Lindquist,2002;Ma et al., 2002). PubMed:14556719
The proteasome activity in the mammalian brain decreases with increasing age (Keller et al., 2002), suggesting that the aged brain is less able to handle the aberrantly folded Abeta PubMed:14556719
Interestingly, tau clearance is known to be impaired in the aging brain [45], supporting the idea that diminished quality control might be conducive to certain tauopathies, such as AD, which are linked to aging PubMed:21882945
In relation to tau biology, FKBP51 enhances the association of Hsp90 with tau, co-localizes with tau in murine neurons, coimmunoprecipitates with tau in AD tissue samples and increases with age in an AD mouse model [136]. PubMed:21882945
Meanwhile, an animal experiment showed that IDE expression will descend with age and diabetes, then resulting in Aβ deposition (Kochkina et al. 2015) PubMed:29626319
Meanwhile, an animal experiment showed that IDE expression will descend with age and diabetes, then resulting in Aβ deposition (Kochkina et al. 2015) PubMed:29626319
The levels of sRAGE consistently decreased with age (R = −0.264, p = <0.001) and with the indices of obesity, such as BMI. However, of special interest was the highly significant and previ-ously not reported independent correlation with fat free mass (p < 0.001). PubMed:25681682
Aging, another risk factor of AD, has been found to activate the NLRP1 inflammasome and upregulate IL-18 and IL-1β levels in the hippocampus of aged mice (Mawhinney et al., 2011) PubMed:24561250
AD is the most common of numerous age-associated brain diseases, and the activity of brain proteasomes appears to decline with age (Keller et al. 2002). PubMed:22908190
Beyond an age-related reduction (Keller et al. 2002), proteasome activities decrease in AD in a brain region–specific manner, particularly in hippocampus, parahippocampal gyrus, superior and middle temporal gyri, and the inferior parietal lobule (Keller et al. 2000), areas that are especially critical for long-term memory formation. PubMed:22908190
Proteome oxidation and instability has been associated with ageing and the progression of several age-related diseases, including cardiovascular disorders, neu- rodegeneration, and cancer [7,95,96]. PubMed:24563850
Proteome is modified post-translationally by either numerous highly regulated enzymatic protein modifications (EPMs) (e.g. phosphorylation, acetylation, ubiquitination, methylation, etc.) or by non-enzymatic protein modifications (NEPMs), which are mostly stochastic and increase with ageing or in age-related diseases (Fig. 1). PubMed:24563850
However, tau aggregates are also observed in the brains of some aged individuals with a condition known as primary age-related tauopathy (PART) PubMed:26631930
Obesity, genetic factors, and aging are some of the most prominent risk factors (Sharma et al., 2006), and in the younger population, previous knee injury is an important contributor to increased prevalence of knee OA – as much as half of those sustaining a knee injury in their 20s had developed posttraumatic knee OA in the following 12 to 14 years (Lohmander et al., 2004, 2007; von Porat et al., 2004). PubMed:30505280
The ageing-associated decrease in paravascular recirculation of CSF and ISF is thought to be responsible, at least in part, for the accumulation of amyloid-β in the brain parenchyma PubMed:30046111
The ageing-associated decrease in paravascular recirculation of CSF and ISF is thought to be responsible, at least in part, for the accumulation of amyloid-β in the brain parenchyma PubMed:30046111
The ageing-associated decrease in paravascular recirculation of CSF and ISF is thought to be responsible, at least in part, for the accumulation of amyloid-β in the brain parenchyma PubMed:30046111
Ageing also leads to progressive lymphatic vessel dysfunction in peripheral tissues PubMed:30046111
The reported findings that ageing is also associated with peripheral lymphatic dysfunction led us to hypothesize that the deterioration of meningeal lymphatic vessels underlies some aspects of age-associated cognitive decline PubMed:30046111
Indeed, and in agreement with a previous study, old mice demonstrate reduced brain perfusion by CSF macromolecules compared to young counterparts (Extended Data Fig. 6a, b) PubMed:30046111
Enrichment analysis revealed, however, changes in gene sets involved in immune and inflammatory responses, phospholipid metabolism, extracellular matrix organization, cellular adhesion and endothelial tube morphogenesis, all of which suggest that there are functional alterations in meningeal LECs with age (Fig. 2c). PubMed:30046111
Enrichment analysis revealed, however, changes in gene sets involved in immune and inflammatory responses, phospholipid metabolism, extracellular matrix organization, cellular adhesion and endothelial tube morphogenesis, all of which suggest that there are functional alterations in meningeal LECs with age (Fig. 2c). PubMed:30046111
Enrichment analysis revealed, however, changes in gene sets involved in immune and inflammatory responses, phospholipid metabolism, extracellular matrix organization, cellular adhesion and endothelial tube morphogenesis, all of which suggest that there are functional alterations in meningeal LECs with age (Fig. 2c). PubMed:30046111
Enrichment analysis revealed, however, changes in gene sets involved in immune and inflammatory responses, phospholipid metabolism, extracellular matrix organization, cellular adhesion and endothelial tube morphogenesis, all of which suggest that there are functional alterations in meningeal LECs with age (Fig. 2c). PubMed:30046111
Enrichment analysis revealed, however, changes in gene sets involved in immune and inflammatory responses, phospholipid metabolism, extracellular matrix organization, cellular adhesion and endothelial tube morphogenesis, all of which suggest that there are functional alterations in meningeal LECs with age (Fig. 2c). PubMed:30046111
Enrichment analysis revealed, however, changes in gene sets involved in immune and inflammatory responses, phospholipid metabolism, extracellular matrix organization, cellular adhesion and endothelial tube morphogenesis, all of which suggest that there are functional alterations in meningeal LECs with age (Fig. 2c). PubMed:30046111
The altered expression of genes involved in the transmembrane receptor protein tyrosine kinase signalling pathway in old mice, namely the downregulation of Cdk5r1, Adamts3 and Fgfr3, indicated possible changes in signalling by lymphangiogenic growth factors in old meningeal LECs (Fig. 2d) PubMed:30046111
The altered expression of genes involved in the transmembrane receptor protein tyrosine kinase signalling pathway in old mice, namely the downregulation of Cdk5r1, Adamts3 and Fgfr3, indicated possible changes in signalling by lymphangiogenic growth factors in old meningeal LECs (Fig. 2d) PubMed:30046111
The altered expression of genes involved in the transmembrane receptor protein tyrosine kinase signalling pathway in old mice, namely the downregulation of Cdk5r1, Adamts3 and Fgfr3, indicated possible changes in signalling by lymphangiogenic growth factors in old meningeal LECs (Fig. 2d) PubMed:30046111
An exponential increase of brain levels of AβOs in aging mice was observed. PubMed:29196815
The risk factors of AD include: increasing age, vascular factors such as smoking, obesity, and diabetes (Reitz and Mayeux 2014) as well as genetic mutations. PubMed:29196815
Dementia is a debilitating condition frequent in ageing populations, and Alzheimer's Disease (AD) accounts for 70% of all dementia cases. AD is characterized by neuropathological hallmarks consisting of an accumulation of Amyloid beta peptide (Ab) in extracellular plaques, intracellular deposits of tau protein, neuronal loss and, more recently, a prominent synaptic loss was identified (Braak and Braak,1991; Masliah et al., 2001; Selkoe,1991; Spires-Jones and Hyman, 2014) PubMed:25514383
However, we identify a possible role of the alpha7 subunit in the normal aging process that should be further investigated PubMed:27522251
The levels of alpha4 and alpha7 nAChR mRNA showed a decrease with aging, whereas the levels of alpha3 mRNA were unchanged in the elderly brain relative to the fetal brain (Hellstro¨m-Lindahl et al 1998) PubMed:11230871
The levels of alpha4 and alpha7 nAChR mRNA showed a decrease with aging, whereas the levels of alpha3 mRNA were unchanged in the elderly brain relative to the fetal brain (Hellstro¨m-Lindahl et al 1998) PubMed:11230871
In addition, a marked reduction in the laminar distribution of [3H]epibatidine binding was observed in control cortical tissue with aging (Figure 1) PubMed:11230871
A significant decrease in [3H]epibatidine binding has been observed with aging in the human cortical brain regions and cerebellum (Marutle et al 1998) PubMed:11230871
The levels of alpha4 and alpha7 nAChR mRNA showed a decrease with aging, whereas the levels of alpha3 mRNA were unchanged in the elderly brain relative to the fetal brain (Hellstro¨m-Lindahl et al 1998) PubMed:11230871
The proteasome activity in the mammalian brain decreases with increasing age (Keller et al., 2002), suggesting that the aged brain is less able to handle the aberrantly folded Abeta PubMed:14556719
Lindquist and colleagues proposed that inhibition of UPS, which can be caused by ageing or following a pharmacological treatment, can lead to accumulation of PrPc in the cytoplasm where it is spontaneously converted into a PrPsc-like species because it is not rapidly degraded by the UPS (Hooper, 2003; Ma and Lindquist,2002;Ma et al., 2002). PubMed:14556719
Lindquist and colleagues proposed that inhibition of UPS, which can be caused by ageing or following a pharmacological treatment, can lead to accumulation of PrPc in the cytoplasm where it is spontaneously converted into a PrPsc-like species because it is not rapidly degraded by the UPS (Hooper, 2003; Ma and Lindquist,2002;Ma et al., 2002). PubMed:14556719
Activity of the deacetylase SIRT1 declines with age, partially owing to limited availability of its co fac- tor, nicotinamide 24,56,156 . PubMed:30116051
Activity of the deacetylase SIRT1 declines with age, partially owing to limited availability of its co fac- tor, nicotinamide 24,56,156 . PubMed:30116051
Loss of neuronal proteostasis, a common feature of the aging brain, is accelerated in neurodegenerative disorders, including different types of tauopathies PubMed:29024336
It is well accepted that loss of proteostasis occurs gradually with age and underlies the basis of severe neurodegenerative disorders such as Parkinson’s disease, Huntington’s disease, Alzheimer’s disease, and other types of frontotemporal dementia (Prahlad & Morimoto, 2009; Voisine et al., 2010; Morimoto & Cuervo, 2014) PubMed:29024336
Interestingly, tau clearance is known to be impaired in the aging brain [45], supporting the idea that diminished quality control might be conducive to certain tauopathies, such as AD, which are linked to aging PubMed:21882945
In relation to tau biology, FKBP51 enhances the association of Hsp90 with tau, co-localizes with tau in murine neurons, coimmunoprecipitates with tau in AD tissue samples and increases with age in an AD mouse model [136]. PubMed:21882945
Meanwhile, an animal experiment showed that IDE expression will descend with age and diabetes, then resulting in Aβ deposition (Kochkina et al. 2015) PubMed:29626319
Meanwhile, an animal experiment showed that IDE expression will descend with age and diabetes, then resulting in Aβ deposition (Kochkina et al. 2015) PubMed:29626319
The levels of sRAGE consistently decreased with age (R = −0.264, p = <0.001) and with the indices of obesity, such as BMI. However, of special interest was the highly significant and previ-ously not reported independent correlation with fat free mass (p < 0.001). PubMed:25681682
Interestingly, the middle-aged rats have higher levels of PTP-1B, lower phosphorylation of IRS-1, Akt, GSK3β, mTOR, and TrkB. Also, the aging process increased Tau phosphorylation and β-amyloid content in the hippocampus region. In summary, this study provides new evidence that aging-related PTP1B increasing, contributing to insulin resistance and the onset of the AD. PubMed:29421605
It is observed that the expression of B55 γ increases and B55 β decreases gradually after birth and are developmentally regulated [28]. PubMed:23454242
It is observed that the expression of B55 γ increases and B55 β decreases gradually after birth and are developmentally regulated [28]. PubMed:23454242
Aging, another risk factor of AD, has been found to activate the NLRP1 inflammasome and upregulate IL-18 and IL-1β levels in the hippocampus of aged mice (Mawhinney et al., 2011) PubMed:24561250
Aging, another risk factor of AD, has been found to activate the NLRP1 inflammasome and upregulate IL-18 and IL-1β levels in the hippocampus of aged mice (Mawhinney et al., 2011) PubMed:24561250
Aging, another risk factor of AD, has been found to activate the NLRP1 inflammasome and upregulate IL-18 and IL-1β levels in the hippocampus of aged mice (Mawhinney et al., 2011) PubMed:24561250
Aging, another risk factor of AD, has been found to activate the NLRP1 inflammasome and upregulate IL-18 and IL-1β levels in the hippocampus of aged mice (Mawhinney et al., 2011) PubMed:24561250
Furthermore, analysis of hippocampal gene expression in aging mice, using publicly available data (NCBI database GDS2082) [73], indicates a significant increase in Otub1 expression with aging (Fig. S4b). PubMed:28083634
The HSP70 and HSP40 family members exhibit significantly altered expression dynamics during aging in the human brain, both being consistently repressed with age (Brehme et al., 2014). PubMed:27491084
The HSP70 and HSP40 family members exhibit significantly altered expression dynamics during aging in the human brain, both being consistently repressed with age (Brehme et al., 2014). PubMed:27491084
Furthermore, sHSPs were found to be consistently upregulated in the aging human brain and in the context of neurodegenerative diseases (Brehme et al., 2014). PubMed:27491084
AD is the most common of numerous age-associated brain diseases, and the activity of brain proteasomes appears to decline with age (Keller et al. 2002). PubMed:22908190
Beyond an age-related reduction (Keller et al. 2002), proteasome activities decrease in AD in a brain region–specific manner, particularly in hippocampus, parahippocampal gyrus, superior and middle temporal gyri, and the inferior parietal lobule (Keller et al. 2000), areas that are especially critical for long-term memory formation. PubMed:22908190
Indeed, studies using model organisms demonstrate that a gradual decline in cellular proteostasis capacity occurs with aging (10). PubMed:23746257
As shown in Caenorhabditis elegans, Drosophila, and the mouse, the ability of cells and tissues to maintain proteostasis declines during aging, concurrent with the capacity to respond to conformational stresses (214–220). PubMed:23746257
Proteome is modified post-translationally by either numerous highly regulated enzymatic protein modifications (EPMs) (e.g. phosphorylation, acetylation, ubiquitination, methylation, etc.) or by non-enzymatic protein modifications (NEPMs), which are mostly stochastic and increase with ageing or in age-related diseases (Fig. 1). PubMed:24563850
Proteome oxidation and instability has been associated with ageing and the progression of several age-related diseases, including cardiovascular disorders, neu- rodegeneration, and cancer [7,95,96]. PubMed:24563850
At more mature ages (DIV14 - DIV21), MAPT localization is mainly found in the axons with only basal levels in the somatodendritic compartment, consistent with earlier findings [20]. PubMed:30145931
At more mature ages (DIV14 - DIV21), MAPT localization is mainly found in the axons with only basal levels in the somatodendritic compartment, consistent with earlier findings [20]. PubMed:30145931
Three transgenic lines were generated based on 1N4R wild-type MAPT or its FTD-17 mutant variants P301L and V337M. The mutant lines showed a stronger Unc phenotype than the wild-type tau lines and the severity of the Unc phenotype progressed with age PubMed:29191965
Cortical neurons of Tg Tau P301S mice also show an in- crease in tau hyperphosphorylation and pSyk with age (Fig. 7). PubMed:28877763
In contrast, microscopic fields of older Tg APPsw mice containing A β deposits exhibit a strong increase in pSyk burden (799.95 ± 130.19%) com- pared to age-matched WT mice. PubMed:28877763
Cortical neurons of Tg Tau P301S mice also show an in- crease in tau hyperphosphorylation and pSyk with age (Fig. 7). PubMed:28877763
However, tau aggregates are also observed in the brains of some aged individuals with a condition known as primary age-related tauopathy (PART) PubMed:26631930
Obesity, genetic factors, and aging are some of the most prominent risk factors (Sharma et al., 2006), and in the younger population, previous knee injury is an important contributor to increased prevalence of knee OA – as much as half of those sustaining a knee injury in their 20s had developed posttraumatic knee OA in the following 12 to 14 years (Lohmander et al., 2004, 2007; von Porat et al., 2004). PubMed:30505280
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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.