scholarly journals Female Mice Reaching Exceptionally High Old Age Have Preserved 20S Proteasome Activities

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1397
Author(s):  
Irene Martínez de Toda ◽  
Suresh I. S. Rattan ◽  
Mónica De la Fuente ◽  
Lorena Arranz
Keyword(s):  
Successful Aging ◽  
Cell Function ◽  
Axillary Lymph Nodes ◽  
20S Proteasome ◽  
Axillary Lymph ◽  
Cell Type ◽  
Female Mice ◽  
Age Related ◽  
Peritoneal Leukocytes ◽  
Old Mice

Oxidized, damaged and misfolded proteins accumulate during aging and contribute to impaired cell function and tissue homeodynamics. Damaged proteins are degraded by cellular clearance mechanisms like the 20S proteasome. Aging relates to low 20S proteasome function, whereas long-lived species show high levels. However, contradictory results exist depending on the tissue or cell type and it is unknown how the 20S proteasome functions in exceptionally old mice. The aim of this study was to investigate two proteasome activities (caspase-like and chymotrypsin-like) in several tissues (lung, heart, axillary lymph nodes, liver, kidney) and cells (peritoneal leukocytes) from adult (28 ± 4 weeks, n = 12), old (76 ± 4 weeks, n = 9) and exceptionally old (128 ± 4 weeks, n = 9) BALB/c female mice. The results show different age-related changes depending on the tissue and the activity considered, so there is no universal decline in proteasome function with age in female mice. Interestingly, exceptionally old mice displayed better maintained proteasome activities, suggesting that preserved 20S proteasome is associated with successful aging.

scholarly journals Histomorphometric Study of Axillary Lymph Nodes in Different Age Groups

2019 ◽  
Vol 08 (04) ◽  
pp. 136-141
Author(s):  
Kafeel Hussain A. ◽  
Shaweez Fathima S. ◽  
V. Sathialakshmi
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Age Groups ◽  
Cross Sectional Study ◽  
Germinal Centers ◽  
Axillary Lymph Nodes ◽  
Strong Impact ◽  
Axillary Lymph ◽  
Cross Sectional ◽  
Age Related

Abstract Background Although some age-related changes in lymph node histoarchitecture have been described, they are seldom taken into account in traditional depictions of lymph nodes. Recently introduced clinical procedures, such as intranodal vaccinations have demonstrated the need for an accurate knowledge of the degenerative processes of lymph nodes. It is thus deemed necessary to obtain a detailed insight into anatomical changes within the lymph node throughout life as age-related degeneration can have a strong impact on the outcome of these new therapeutic strategies. Aim To study the size and shape of the lymph nodes and to establish the age-dependent histoarchitectural changes in the lymph nodes in different age groups. Materials and Methods A cross-sectional study was conducted in a total of 35 axillary lymph nodes. The adult axillary group of lymph nodes were from subjects aged between 18 and 70 years. The fetal lymph nodes were collected from 8 stillborn fetuses between 37 and 42 weeks. Thickness of the cortex and diameter of the germinal centers were measured using ocular and stage micrometer. Results None of the fetal lymphocytic follicles showed evidence of a prominent germinal center. The germinal centers of young adults were not only more numerous but also larger in size when compared with the old. An age-related involution of the paracortical region was witnessed in the axillary lymph nodes. No evidence of lipomatous atrophy was encountered in any of the fetal lymph nodes. Interesting evidence of it was encountered in younger age groups. However, this was the most prominent feature in the older groups.

scholarly journals Cortical bone gain following loading is site-specifically enhanced by prior and concurrent disuse in aged male mice

2019 ◽  
Author(s):  
Gabriel Galea ◽  
Peter J Delisser ◽  
Lee Meakin ◽  
Lance E Lanyon ◽  
Joanna S Price ◽  
...  
Keyword(s):  
Bone Mass ◽  
Cortical Bone ◽  
List Type ◽  
Male Mice ◽  
Site Specific ◽  
Female Mice ◽  
Age Related ◽  
Sciatic Neurectomy ◽  
Bone Gain ◽  
Old Mice

AbstractThe primary aim of bone anabolic therapies is to strategically increase bone mass in skeletal regions likely to experience high strains. This is naturally achieved by mechanical loading of the young healthy skeleton. However, these bone anabolic responses fail with age. Here, we applied site specificity analysis to map regional differences in bone anabolic responses to axial loading of the tibia (tri-weekly, for two weeks) between young (19-week-old) and aged (19-month-old), male and female mice. Loading increased bone mass specifically in the proximal tibia in both sexes and ages. Young female mice gained more cortical bone than young males in specific regions of the tibia. However, these site-specific sex difference were lost with age such that bone gain following loading was not significantly different between old males and females. Having previously demonstrated that prior and concurrent disuse enhances bone gain following loading in old females, we established whether this “rescue” is sex-specific. Old male mice were subjected to sciatic neurectomy or sham surgery, and tri-weekly loading was initiated four days after surgery. Disuse augmented cortical bone gain in response to loading in old male mice, but only in the regions of the tibia which were load-responsive in the young. Increased understanding of how locally-activated load-responsive processes lead to site-specific bone formation, and how the age-related diminution of these processes can be site-specifically enhanced by disuse, may lead to the next generation of strategic bone anabolic therapies.HighlightsSex differences in cortical tissue area of young and old mice are not site-specificThe loading response in young, but not old, mice is sex- and site-specificThe cortical loading response is site-specifically enhanced by disuse in old mice of both sexesThe trabecular loading response can be rescued by disuse in old male, but not female, mice

scholarly journals Prevention of age-related T cell apoptosis defect in CD2-fas-transgenic mice.

1995 ◽  
Vol 182 (1) ◽  
pp. 129-137 ◽  
Author(s):  
T Zhou ◽  
C K Edwards ◽  
J D Mountz
Keyword(s):  
T Cells ◽  
T Cell ◽  
Transgenic Mice ◽  
Cell Function ◽  
Thymic Involution ◽  
Age Related ◽  
Induced Apoptosis ◽  
And Function ◽  
Old Mice ◽  
Young Mice

T cell dysfunction and thymic involution are major immunologic abnormalities associated with aging. Fas (CD95) is a bifunctional molecule that is critical for apoptosis and stimulation during T cell development, but the role of Fas during aging has not been determined. Fas expression and function on T cells from old (22-26-mo-old) mice was compared with young (2-mo-old) mice and old CD2-fas-transgenic mice. Fas expression and ligand-induced apoptosis were decreased on T cells from old mice compared with young mice. This correlated with an age-related increase in CD44+Fas- T cells. There was a marked decrease in the proliferation of T cells from old mice after anti-CD3 stimulation compared with young mice. Anti-CD3-stimulated T cells from young mice exhibited increased production of interleukin (IL)-2 and decreased production of interferon-gamma and IL-10 compared with old mice. There was an age-related decrease in the total thymocyte count from 127 +/- 10 cells in young mice compared with 26 +/- 8 x 10(6) in old mice. In 26-mo-old CD2-fas-transgenic mice, Fas and CD44 expression, Fas-induced apoptosis, T cell proliferation, and cytokine production were comparable to that of the young mice. These results suggest that T cell senescence with age is associated with defective apoptosis, and that the CD2-fas transgene allows maintenance of Fas apoptosis function and T cell function in aged mice comparable to that of young mice.

Levels of retinyl palmitate and retinol in stratum corneum, epidermis and dermis of SKH-1 mice

2006 ◽  
Vol 22 (3) ◽  
pp. 103-112 ◽  
Author(s):  
Jian Yan ◽  
Qingsu Xia ◽  
Peggy Webb ◽  
Alan R Warbritton ◽  
Wayne G Wamer ◽  
...  
Keyword(s):  
Stratum Corneum ◽  
Retinyl Palmitate ◽  
Related Effect ◽  
Intact Skin ◽  
Female Mice ◽  
Age Related ◽  
Predominant Component ◽  
Animal Remains ◽  
Old Mice

Vitamin A (retinol) regulates many biological functions, including epidermal cell growth. Retinyl palmitate (RP) is the major esterified form of retinol and the predominant component of retinoids in the skin; however, how endogenous levels of RP and retinol in the skin are affected by the age of the animal remains unknown. Furthermore, the levels of retinol and RP in the various skin layers- the stratum corneum, epidermis and dermis of skin- have not been reported. In this paper, we report the development of a convenient method for separation of the skin from SKH-1 female mice into the stratum corneum, epidermis, and dermis and the determination of the levels of RP and retinol in the three fractions by HPLC analysis. The total quantities of RP and retinol from the stratum corneum, epidermis, and dermis are comparable to those extracted from the same amount of intact skin from the same mouse. There was an age-related effect on the levels of RP and retinol in the skin and liver of female mice. An age-related effect was also observed in the stratum corneum, epidermis, and dermis. The levels of RP and retinol were highest in the epidermis of 20-week-old mice, and decreased when the age increased to 60- and 68-weeks. The total amount of RP at 20 weeks of age was found to be 1.52 ng/mg skin, and decreased about 4-fold at 60- and 68-weeks of age. A similar trend was found for the effects of age on the levels of retinol.

scholarly journals Integrated in vivo quantitative proteomics and nutrient tracing reveals age-related metabolic rewiring of pancreatic β-cell function

2018 ◽  
Author(s):  
Matthew Wortham ◽  
Jacqueline R. Benthuysen ◽  
Martina Wallace ◽  
Jeffrey N. Savas ◽  
Francesca Mulas ◽  
...  
Keyword(s):  
Cell Function ◽  
Coupling Factor ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Age Related ◽  
Β Cell Function ◽  
One Year ◽  
Old Mice ◽  
Age Related Changes

SummaryPancreatic β-cell physiology changes substantially throughout life; yet, the mechanisms that drive these changes are poorly understood. Here, we performed comprehensive in vivo quantitative proteomic profiling of pancreatic islets from adolescent and one-year-old mice. The analysis revealed striking differences in abundance of enzymes controlling glucose metabolism. We show that these changes in protein abundance are associated with higher activities of glucose metabolic enzymes involved in coupling factor generation as well as increased activity of the coupling factor-dependent amplifying pathway of insulin secretion. Nutrient tracing and targeted metabolomics demonstrated accelerated accumulation of glucose-derived metabolites and coupling factors in islets from one-year-old mice, indicating that age-related changes in glucose metabolism contribute to improved glucose-stimulated insulin secretion with age. Together, our study provides the first in-depth characterization of age-related changes in the islet proteome and establishes metabolic rewiring as an important mechanism for age-associated changes in β-cell function.

scholarly journals Megakaryocyte Progenitor Cell Function is Enhanced Upon Aging Despite the Functional Decline of Aged Hematopoietic Stem Cells

2021 ◽  
Author(s):  
Donna M. Poscablo ◽  
Atesh K. Worthington ◽  
Stephanie Smith-Berdan ◽  
E. Camilla Forsberg
Keyword(s):  
Cell Function ◽  
Functional Decline ◽  
List Type ◽  
Hematopoietic Stem ◽  
Cell Numbers ◽  
Age Related ◽  
Genome Wide ◽  
Expansion Capacity ◽  
Old Mice

SUMMARYAge-related morbidity is associated with a decline in hematopoietic stem cell (HSC) function, but the mechanisms of HSC aging remain unclear. We performed heterochronic HSC transplants followed by quantitative analysis of cell reconstitution. While young HSCs outperformed old HSCs in young recipients, young HSCs unexpectedly failed to outcompete the old HSCs of aged recipients. Interestingly, despite substantial enrichment of megakaryocyte progenitors (MkPs) in old mice in situ and reported platelet (Plt) priming with age, transplanted old HSCs were deficient in reconstitution of all lineages, including MkPs and Plts. We therefore performed functional analysis of young and old MkPs. Surprisingly, old MkPs displayed unmistakably greater regenerative capacity compared to young MkPs. Transcriptome analysis revealed putative molecular regulators of old MkP expansion. Collectively, these data demonstrated that aging affects HSCs and megakaryopoiesis in fundamentally different ways: whereas old HSCs functionally decline, MkPs gain expansion capacity upon aging.HIGHLIGHTSFrequencies and total cell numbers of HSCs and MkPs were increased upon agingReconstitution deficit by old HSCs was observed by chimerism and absolute cell numbersYoung HSCs did not have competitive advantage over old HSCs in aged recipient miceOld MkPs display remarkable capacity to engraft, expand, and reconstitute plateletsAging is associated with changes in MkP genome-wide expression signatures

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