Nutritional Influences on Aging of Fischer 344 Rats: II. Pathology

Maeda, Hidefumi; Gleiser, Chester A.; Masoro, Edward J.; Murata, I.; McMahan, C. Alex; Yu, Bo

doi:10.1093/geronj/40.6.671

Cited by 363 publications

(203 citation statements)

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“…Loss of myocytes in the aging heart may be due to apoptosis, which has been linked to cytochrome c release and oxidative stress (64). Based on the transcriptional profile of the hearts of CR mice, we suggest that CR protects myocytes from age-associated death, a conclusion that is consistent with the previous observation that CR prevents cardiomyopathy in rats (65,66). Surprisingly, we found no evidence that aging in the heart is associated with a transcriptional profile indicative of an oxidative stress response, as previously demonstrated for skeletal muscle (6) and brain (7) of C57Bl6 mice.…”

Section: Discussionsupporting

confidence: 90%

Transcriptional profiles associated with aging and middle age-onset caloric restriction in mouse hearts

Lee

Allison

Brand

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

289

218

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To provide a global analysis of gene expression in the aging heart, we monitored the expression of 9,977 genes simultaneously in 5-and 30-month-old male B6C3F1 mice by using high-density oligonucleotide microarrays and several statistical techniques. Aging was associated with transcriptional alterations consistent with a metabolic shift from fatty acid to carbohydrate metabolism, increased expression of extracellular matrix genes, and reduced protein synthesis. Caloric restriction (CR) started at 14 months of age resulted in a 19% global inhibition of age-related changes in gene expression. Interestingly, CR also resulted in alterations in gene expression consistent with preserved fatty acid metabolism, reduced endogenous DNA damage, decreased innate immune activity, apoptosis modulation, and a marked cytoskeletal reorganization. These observations provide evidence that aging of the heart is associated with specific transcriptional alterations, and that CR initiated in middle age may retard heart aging by inducing a profound transcriptional reprogramming.W hen started either early in life or at middle age, caloric restriction (CR) increases average and maximum lifespan, and reduces the incidence and delays the onset of spontaneous cancers and several other age-related diseases (1). Additionally, CR reduces the age-associated increase in reactive oxygen species (ROS)-induced molecular damage (2-5). Previously, we have used high-density oligonucleotide arrays to define aging and CR-related transcriptional alterations in mouse skeletal muscle (6) and brain (7). These reports provided evidence for an age-associated stress response characterized by the induction of heat-shock factors and other oxidative stress-induced transcripts. CR prevented these age-related alterations completely or partially. Both studies provided further support for the concept that oxidative stress may be an important, and perhaps underlying cause of the aging process of postmitotic tissues.The cardiac myocyte is the most energy demanding cell in the body, contracting constantly, 3 billion times or more in the average human lifespan (8), requiring large supplies of high-energy phosphates (9). Age-related changes in human and rodent hearts include a reduction in the number of myocytes (10, 11), myocyte hypertrophy (11, 12), cardiac fibrosis (13), lipofuscin pigment accumulation (14), a reduction in calcium transport across sarcoplasmic reticulum membrane (15), and alterations in the response to ␤-adrenergic stimulation (16). Collectively, these alterations likely contribute to age-related heart diseases being the leading cause of mortality in the U.S. (17). CR reduces the severity of spontaneous cardiomyopathy in male Sprague-Dawley rats (18) and prevents age-associated alterations in late diastolic function in B6D2F 1 mice (19). At the molecular level, CR reduces the concentration of both 8-hydroxydeoxyguanosine in DNA (20) and dityrosine cross-linking of proteins (21) in the heart of aging mice, and prevents somatic mitochondrial genomic rear...

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Section: Discussionsupporting

confidence: 90%

Transcriptional profiles associated with aging and middle age-onset caloric restriction in mouse hearts

Lee

Allison

Brand

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

289

218

View full text Add to dashboard Cite

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“…Similarly, we cannot rule out sex-associated differences in brain mitochondrial aging. Because male rats have a higher incidence of age-related pathophysiology that might adversely confound our measurements (Maeda et al, 1985;Fox et al, 2002), the absence of central nervous system (CNS) mitochondria from males at the oldest age studied could have biased our data in the direction of no change. We did, however, see mild deterioration above 32 months.…”

Section: Discussionmentioning

confidence: 99%

Age‐related changes in regional brain mitochondria from Fischer 344 rats

et al. 2005

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SummaryBrain mitochondrial function has been posited to decline with aging. In order to test this hypothesis, cortical and striatal mitochondria were isolated from Fischer 344 rats at 2, 5, 11, 24 and 33 months of age. Mitochondrial membrane potential remained stable through 24 months, declining slightly in mitochondria from both brain regions at 33 months. The ability of calcium to induce mitochondrial swelling and depolarization, characteristics of the permeability transition, was remarkably stable through 24 months of age and increased at advanced ages only for cortical, but not striatal, mitochondria. Striatal mitochondria were more sensitive to calcium than were cortical mitochondria throughout the first 2 years of life. A two-fold increased resistance to calcium was observed in striatal mitochondria between 5 and 11 months. Although these measurements do demonstrate changes in mitochondrial function with aging, the changes in polarization are relatively small and the increased cortical susceptibility to the permeability transition only occurred at very advanced ages. Thus mitochondrial decline with advanced age depends upon brain region.

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“…Renal involvement was graded from 0-3 as determined by interstitial fibrosis and nephropathy. The severity of nephropathy was scored using the method of Maeda and colleagues with some modifications (14,15).…”

Section: Methodsmentioning

confidence: 99%

Fibrotic response to angiotensin II is blunted in the kidney, but not in the heart, in insulin-sensitive long-lived transgenic dwarf rats

Sato

Ashizawa²,

Ohtsuru³

et al. 2007

Int J Mol Med

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Abstract. Insulin resistance is a characteristic feature of cardiovascular and renal diseases, and angiotensin II (Ang II) has been suggested to induce insulin resistance. The aims of this study were to elucidate the effect of chronic Ang II infusion on vascular reactivity and organ damage in insulinsensitive rats. We confirmed the following three points. First, there was no significant difference in pressor response to chronic Ang II infusion (600 ng/kg/min) between insulinsensitive transgenic rats (Tg) and control rats (C). Second, there was no significant difference in cardiac hypertrophy and fibrosis by chronic Ang II infusion between the two groups. However, third, fibrotic response to chronic Ang II infusion evaluated by histopathological scoring in the kidney was significantly decreased in insulin-sensitive transgenic rats (renal fibrosis and nephropathy score: C+Ang II vs Tg+Ang II; 2.5 vs 1.3; p<0.05). Furthermore, the expression of TGF-ß, a fibrosis indicator, was also significantly suppressed in the kidneys of the transgenic rats (TGF-ß1/ GAPDH ratio: C+Ang II vs Tg+Ang II; 1.15 vs 0.81; p<0.05). This result indicates that the growth hormone/insulin-like growth factor-1 axis is critically involved in the development of renal injury and fibrosis, rather than hypertension, cardiac hypertrophy, and cardiac fibrosis induced by chronic Ang II administration.

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Nutritional Influences on Aging of Fischer 344 Rats: II. Pathology

Cited by 363 publications

References 0 publications

Transcriptional profiles associated with aging and middle age-onset caloric restriction in mouse hearts

Transcriptional profiles associated with aging and middle age-onset caloric restriction in mouse hearts

Age‐related changes in regional brain mitochondria from Fischer 344 rats

Fibrotic response to angiotensin II is blunted in the kidney, but not in the heart, in insulin-sensitive long-lived transgenic dwarf rats

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