Quantitative and Qualitative Alterations of Acute-phase Proteins in Healthy Elderly Persons

Ballou, Stanley P.; Lozanski, Gerard; Hodder, Sally; Rzewnicki, Debra; Mion, Lorraine C.; Sipe, Jean D.; Ford, Amasa B.; Kushner, Irving

doi:10.1093/ageing/25.3.224

Cited by 144 publications

(90 citation statements)

References 30 publications

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“…Serum Amyloid A (Saa) is a component of a group of major acute phase proteins, and its expression increases in response to infection or systemic inflammation. In agreement with previous works (Vranckx et al 1995;Ballou et al 1996), the present study found that the expression levels of this gene family (consisting, in mouse, of three active genes, Saa1, Saa2, Saa3) were 9-to 55-fold higher in old mice compared to young animals. These results suggest that inflammation is a component of aging process in the liver, according to the concept of the existence in aged animals of a state of chronic inflammation in the absence of Bstressors.^Genes involved in immune response were also up-regulated in aged liver; particularly striking was the 40-fold increase in the expression of lipocalin 2, a novel autocrine and paracrine adipokine, which acts as an antagonist of inflammatory molecules.…”

Section: Resultssupporting

confidence: 93%

Global gene expression profile of normal and regenerating liver in young and old mice

Pibiri

Sulas

Leoni

et al. 2015

AGE

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The ability of the liver to regenerate and adjust its size after two/third partial hepatectomy (PH) is impaired in old rodents and humans. Here, we investigated by microarray analysis the expression pattern of hepatic genes in young and old untreated mice and the differences in gene expression profile following PH. Of the 10,237 messenger RNAs that had detectable expression, only 108 displayed a greater than 2-fold modification in gene expression levels between the two groups.These genes were involved in inflammatory and immune response, xenobiotics, and lipid and glucose metabolism. To identify the genes responsible for the different regenerative response, 10-week and 18-monthold mice subjected to PH were sacrificed at different time intervals after surgery. The results showed that 2463 transcripts had significantly different expression post PH between the two groups. However, in spite of impaired liver regeneration in old mice, cell cycle genes were similarly modified in both groups, the only exception being cyclin D1 gene which was up-regulated soon after PH in young mice, but mostly down-regulated in aged animals. Surprisingly, while in young hepatectomized mice, Yap messenger RNA (mRNA) expression was not significantly enhanced and protein expression essentially reflected the progression into cell cycle, its mRNA and protein levels were robustly increased in the liver of aged animals. Furthermore, a significant change of the age-related expression of the size regulator Yesassociated protein (YAP) was observed. Unexpectedly, while in young hepatectomized mice, Yap mRNA expression was not significantly enhanced and protein expression essentially reflected the progression into cell cycle, its mRNA and protein levels were robustly increased in the liver of aged animals. Moreover, when PH was performed on mitogen-induced enlarged livers, the earlier restoration of the original liver mass compared to animals subjected to PH only led to YAP downregulation concomitantly with cyclin D1 up-regulation. Our data suggest that YAP activation is a size-dependent homeostatic mechanism that does not necessarily reflect cell cycle progression.

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Section: Resultssupporting

confidence: 93%

Global gene expression profile of normal and regenerating liver in young and old mice

Pibiri

Sulas

Leoni

et al. 2015

AGE

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“…Another marker of inflammation is Creactive protein (CRP), which is produced in the liver largely in response to elevations in IL-6. This general marker of inflammation is also elevated in older adults relative to young ones (Ballou et al, 1996). All of these specific changes put older individuals at an increased risk for the diseases mentioned above, including but not limited to cardiovascular disease.…”

Section: Age and Immune Functionmentioning

confidence: 97%

Stress, Age, and Immune Function: Toward a Lifespan Approach

2006

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Both aging processes and psychological stress affect the immune system: Each can dysregulate immune function with a potentially substantial impact on physical health. Worse, the effects of stress and age are interactive. Psychological stress can both mimic and exacerbate the effects of aging, with older adults often showing greater immunological impairment to stress than younger adults. In addition, stressful experiences very early in life can alter the responsiveness of the nervous system and immune system. We review the unique impact of aging and stress on immune function, followed by evidence of interactions between age and stress. Further, we suggest that prenatal or early life stress may increase the likelihood of maladaptive immune responses to stress in late life. An understanding of the interactive effects of stress and age is critical to efforts to determine underlying mechanisms, clarify the directionality of effects, and develop effective interventions in early and late life.

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“…In addition to ECM accumulation, inflammation is a key component of cardiac aging (13,48). Higher levels of circulating proinflammatory cytokines are observed in elderly people, even in the absence of chronic disease (3,8,16,50). In old mice, the cardiac expression of inflammatory genes increases compared with that in young mice (56).…”

mentioning

confidence: 99%

Secreted protein acidic and rich in cysteine facilitates age-related cardiac inflammation and macrophage M1 polarization

Toba

Brás

Baicu

et al. 2015

American Journal of Physiology-Cell Physiology

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Toba H, de Castro Brás LE, Baicu CF, Zile MR, Lindsey ML, Bradshaw AD. Secreted protein acidic and rich in cysteine facilitates age-related cardiac inflammation and macrophage M1 polarization. Am J Physiol Cell Physiol 308: C972-C982, 2015. First published April 15, 2015; doi:10.1152/ajpcell.00402.2014.-To investigate the role of secreted protein acidic and rich in cysteine (SPARC) in age-related cardiac inflammation, we studied six groups of mice: young (3-5 mo old), middle-aged (10 -12 mo old), and old (18 -29 mo old) C57BL/6 wild-type (WT) and SPARC-null (Null) mice (n ϭ 7-10/group). Cardiac function and structure were determined by echocardiography. The left ventricle was used for cytokine gene array and macrophage quantification by immunohistochemistry. Macrophage infiltration increased with age in WT (n ϭ 5-6/group, P Ͻ 0.05 for young vs. old), but not in Null. Proinflammatory markers (Ccl5, Cx3cl1, Ccr2, and Cxcr3) increased in middle-aged and old WT, whereas they were increased only in old Null compared with respective young (n ϭ 5-6/group, P Ͻ 0.05 for all). These results suggest that SPARC deletion delayed age-related cardiac inflammation. To further assess how SPARC affects inflammation, we stimulated peritoneal macrophages with SPARC (n ϭ 4). SPARC treatment increased expression of proinflammatory macrophage M1 markers and decreased anti-inflammatory M2 markers. Echocardiography (n ϭ 7-10/group) revealed an age-related increase in wall thickness of the left ventricle in WT (0.76 Ϯ 0.02 mm in young vs. 0.91 Ϯ 0.03 mm in old; P Ͻ 0.05) but not in Null (0.78 Ϯ 0.01 mm in young vs. 0.84 Ϯ 0.02 mm in old). In conclusion, SPARC deletion delayed age-related increases in macrophage infiltration and proinflammatory cytokine expression in vivo and in vitro. SPARC acts as an important mediator of age-related cardiac inflammation by increasing the expression of macrophage M1 markers and decreasing M2 markers.

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Quantitative and Qualitative Alterations of Acute-phase Proteins in Healthy Elderly Persons

Cited by 144 publications

References 30 publications

Global gene expression profile of normal and regenerating liver in young and old mice

Global gene expression profile of normal and regenerating liver in young and old mice

Stress, Age, and Immune Function: Toward a Lifespan Approach

Secreted protein acidic and rich in cysteine facilitates age-related cardiac inflammation and macrophage M1 polarization

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