Analysis Tools
mortality/aging
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• 44% of mice died between 8 and 18 months of age; in most cases cause of death was not determined
• 2 of 54 mice (12 and 14 months of age) developed an acute autoimmune syndrome, including polyarteritis, acute renal tubular necrosis and acute glomerular thrombosis, that could be interpreted as the cause of death
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• mice developed multiple early aging signs including lordokyphosis, lack of vigor, inability to accumulate fat, reduced ability to tolerate stress, and premature death
• however, mice appeared morphologically normal up to 6 months of age
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growth/size/body
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• in males, body weight was significantly decreased at 2, 4-5, and 11-15 months of age
• in females, body weight was significantly decreased only at 11-15 months of age, with a non-significant trend towards reduction observed at 2 and 4-5 months
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• males failed to gain weight after 4-5 months of age, whereas wild-type males still gained weight at 11-15 months
• females continued to gain weight even at 11-15 months, although at a slower rate than wild-type females
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immune system
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• BrdU incorporation was significantly decreased in CD4-CD8- (double negative), CD4+CD8+ (double positive), CD4 +CD8- (CD4 single positive) and CD4 -CD8+ (CD8 single positive) cells, indicating that bone marrow-derived T cell progenitors have a reduced tissue repopulation ability
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• total thymocyte numbers were significantly decreased
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• at 6 months of age, the proportion of CD11b+F4/80+ macrophages in spleen was significantly higher than in wild-type mice (5.5 % vs 3.7%)
• however, the proportion of splenic CD11b+CD11c+ dendritic cells was normal
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• at 6 months of age, the proportion of splenic CD11b+F4/80+Gr1+ cells (corresponding to inflammatory monocytes) was increased by ~30%, suggesting chronic inflammation
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• at 6 months of age, mice showed an increased number of inflammatory monocytes in peripheral blood and spleen
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hematopoietic system
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• BrdU incorporation was significantly decreased in CD4-CD8- (double negative), CD4+CD8+ (double positive), CD4 +CD8- (CD4 single positive) and CD4 -CD8+ (CD8 single positive) cells, indicating that bone marrow-derived T cell progenitors have a reduced tissue repopulation ability
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• total thymocyte numbers were significantly decreased
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• at 6 months of age, the proportion of CD11b+F4/80+ macrophages in spleen was significantly higher than in wild-type mice (5.5 % vs 3.7%)
• however, the proportion of splenic CD11b+CD11c+ dendritic cells was normal
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• at 6 months of age, the proportion of splenic CD11b+F4/80+Gr1+ cells (corresponding to inflammatory monocytes) was increased by ~30%, suggesting chronic inflammation
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• at 6 months of age, the number of Gr1 + myeloid cells in peripheral blood was significantly higher than in wild-type mice (37% vs 24%)
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renal/urinary system
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• 2 of 54 mice (12 and 14 months of age) developed acute renal tubular necrosis
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skeleton
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• 50% of mice showed signs of lordokyphosis by 9-12 months of age, not observed in age-matched wild-type mice
• ~80% of developed lordokyphosis by 18 months
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cellular
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• cauda epididymal sperm count was significantly reduced at 11-12 months, but not at 6 months of age, indicating a premature decrease in sperm count
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• 2 of 54 mice (12 and 14 months of age) developed acute renal tubular necrosis
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• sperm motility was significantly reduced at 11-12 months of age
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• BrdU incorporation was significantly decreased in CD4-CD8- (double negative), CD4+CD8+ (double positive), CD4 +CD8- (CD4 single positive) and CD4 -CD8+ (CD8 single positive) cells, indicating that bone marrow-derived T cell progenitors have a reduced tissue repopulation ability
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• both primary mouse embryonic fibroblasts (MEFs) and immortalized kidney epithelial cells (iKECs) showed significantly lower maximal respiration (MR) and reserve respiratory capacity (RRC) than wild-type cells, indicating a reduced ability of cells to produce additional ATP in response to increased energy demands
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behavior/neurological
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• mice of pup-bearing age were extremely sensitive to stress-inducing environments, such as increased traffic and prolonged light exposure after installation of a new hood close to the mating cages
• under poor environmental conditions, both frequency of pregnancies and maternal behavior were decreased, indicating reduced ability to tolerate stress
• however, normal breeding and maternal behavior were restored shortly after cages were placed in the quiet and darker corner of the room and supplemented with shredded paper and igloos for nesting
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• mothers failed to feed their newborns under stress-inducing environmental conditions; all pups from occasional litters born during this time died due to negligence
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reproductive system
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• cauda epididymal sperm count was significantly reduced at 11-12 months, but not at 6 months of age, indicating a premature decrease in sperm count
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• sperm motility was significantly reduced at 11-12 months of age
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• at 16-18 months of age, some males showed enlarged seminal vesicles, an infrequent aging lesion that occurs spontaneously in wild-type males at 24 months or later
• premature enlargement of seminal vesicles included asymmetrical enlargement, symmetrical enlargement, and enlargement with discoloration
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small testis
(
J:309768
)
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• at 11-12 months of age, ~10% of males showed a symmetrical or unilateral reduction in testis size, not observed in age-matched wild-type males
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• occasionally, adult males showed unilateral or bilateral testes degeneration with marked mineralization in some cases
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• some aging males showed marked mineralization in the cauda epididymis
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• at 11-12 months of age, ~10% of males showed a symmetrical or unilateral reduction in cauda size, not observed in age-matched wild-type males
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• frequency of pregnancies was severely reduced under stress-inducing environmental conditions
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cardiovascular system
endocrine/exocrine glands
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• total thymocyte numbers were significantly decreased
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• at 16-18 months of age, some males showed enlarged seminal vesicles, an infrequent aging lesion that occurs spontaneously in wild-type males at 24 months or later
• premature enlargement of seminal vesicles included asymmetrical enlargement, symmetrical enlargement, and enlargement with discoloration
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small testis
(
J:309768
)
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• at 11-12 months of age, ~10% of males showed a symmetrical or unilateral reduction in testis size, not observed in age-matched wild-type males
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• occasionally, adult males showed unilateral or bilateral testes degeneration with marked mineralization in some cases
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homeostasis/metabolism
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• 2 of 54 mice (12 and 14 months of age) developed acute glomerular thrombosis
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• primary MEFs and immortalized kidney epithelial cells (iKECs) showed significantly altered dynamics of the cellular calcium response
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• mice showed increased sensitivity to the anesthetics avertin, pentobarbital and chloral hydrate than wild-type mice
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integument
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• in a hair-growth assay, none of five 12-month-old mice showed hair regrowth at 10 days and all of them failed to close the shaved area at 3 months post-shaving
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