Gene expression profiling studies of aging in cardiac and skeletal muscles

Prolla, Tomas A.

doi:10.1016/j.cardiores.2005.01.005

Cited by 93 publications

(70 citation statements)

References 69 publications

(71 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The aged heart changes its metabolism to glucose consumption, with repressed fatty acid use. 36 Perhaps an increase in the availability of fatty acids for storage promotes commitment of stem cells toward the adipocyte lineage. It is not clear whether met- Reduced TGF-␤1-dependent Smad3 activation in fibroblasts derived from aged animals.…”

Section: Rescue Of Defective Function Requires Ampk Activationmentioning

confidence: 99%

Defective Myofibroblast Formation from Mesenchymal Stem Cells in the Aging Murine Heart

Cieslik

Trial

Entman

2011

The American Journal of Pathology

View full text Add to dashboard Cite

Cardiac fibroblasts are the most prevalent cell type in the heart. These cells exert a critical role in regulating normal myocardial function and in the adverse myocardial remodeling that occurs after myocardial infarction (MI). 1 Irreversible cardiomyocyte damage owing to cessation of oxygen supply during MI leads to necrosis, which stimulates inflammatory reactions that trigger reparative pathways and activate cells to form a scar. Cytokines released by inflammatory infiltrating leukocytes promote endogenous mesenchymal stem cell (MSC) proliferation and migration toward the infarct site, followed by differentiation into fibroblasts that deposit scar-forming collagen. The fibroblasts mature into myofibroblasts, expressing scar-contracting ␣-smooth muscle actin (␣-SMA). 2 Resident fibroblasts also become activated and participate in this process. After several weeks, a mature scar is formed, and most of the myofibroblasts undergo apoptosis. [3][4][5] We have previously established in a model of mouse MI that, compared with young animals, aged mice demonstrate greater infarct expansion and less effective myocardial repair. 6 Defective scar formation arises from a decreased number of myofibroblasts and diminished collagen deposition in the infarct, which results in a structurally unstable scar formed by loose connective tissue. 7 Evidence indicates that multipotent cells can be generated in vitro from several adult organs including the heart. 8 Tissue-resident progenitor cells of mesenchymal origin can differentiate into myogenic, adipocytic, chondrocytic, osteoblastic, and fibroblastic lineages. 9 -11 The potential of those stem cells to differentiate decreases

show abstract

Section: Rescue Of Defective Function Requires Ampk Activationmentioning

confidence: 99%

Defective Myofibroblast Formation from Mesenchymal Stem Cells in the Aging Murine Heart

Cieslik

Trial

Entman

2011

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…Involvement of cell cycle regulatory mechanisms in senescence has been shown in proliferating cells. However, few studies of senescence in cardiomyocytes are reported, because cardiomyocyte is terminally differentiated cell (Torella et al ., 2004;Park & Prolla, 2005). It is important to determine whether cell cycle regulators play key roles in senescence of cardiomyocytes.…”

Section: Introductionmentioning

confidence: 99%

Induction of premature senescence in cardiomyocytes by doxorubicin as a novel mechanism of myocardial damage

Maejima¹,

Adachi²,

Ito³

et al. 2007

Aging Cell

182

150

View full text Add to dashboard Cite

SummaryCellular senescence is an important phenomenon in decreased cellular function. Recently, it was shown that cellular senescence is induced in proliferating cells within a short period of time by oxidative stresses. This phenomenon is known as premature senescence. However, it is still unknown whether premature senescence can be also induced in cardiomyocytes. The aim of the present study was to investigate whether a senescence-like phenotype can be induced in cardiomyocytes by oxidative stress. In cardiomyocytes obtained from aged rats (24 months of age), the staining for senescence-associated β β β β -galactosidase increased significantly and the protein or RNA levels of cyclin-dependent kinase inhibitors increased compared to those of young rats. Decreased cardiac troponin I phosphorylation and telomerase activity were also observed in aged cardiomyocytes. Treatment of cultured neonatal rat cardiomyocytes with a low concentration of doxorubicin (DOX) (10 -7 mol L -1 ) did not induce apoptosis but did induce oxidative stress, which was confirmed by 2′ ′ ′ ′ ,7′ ′ ′ ′ -dichlorofluorescin diacetate staining. In DOX-treated neonatal cardiomyocytes, increased positive staining for senescence-associated β β β β -galactosidase, cdk-I expression, decreased cardiac troponin I phosphorylation, and decreased telomerase activity were observed, as aged cardiomyocytes. Alterations in mRNA expression typically seen in aged cells were observed in DOX-treated neonatal cardiomyocytes. We also found that promyelocytic leukemia protein and acetylated p53, key proteins involved in stressinduced premature senescence in proliferating cells, were associated with cellular alterations of senescence in DOX-treated cardiomyocytes. In conclusion, cardiomyocytes treated with DOX showed characteristic changes similar to cardiomyocytes of aged rats. promyelocytic leukemiarelated p53 acetylation may be an underlying mechanism of senescence-like alterations in cardiomyocytes. These findings indicate a novel mechanism of myocardial dysfunction induced by oxidative stress.

show abstract

“…Likewise, culturing HeLa cells with serum from CR rats induces expression of mitochondrial genes, and these changes are associated with an increased number of mitochondria per cell compared with cells cultured in serum from ad libitum fed rats (5). Certainly, CR induces expression of genes involved in mitochondrial energy metabolism in many tissues, including skeletal muscle, heart, and white adipose tissue (4,(6)(7)(8). The skeletal muscle response to CR is particularly interesting for two reasons.…”

mentioning

confidence: 99%

Skeletal muscle transcriptional coactivator PGC-1α mediates mitochondrial, but not metabolic, changes during calorie restriction

Finley

Lee

Souza

et al. 2012

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

View full text Add to dashboard Cite

Calorie restriction (CR) is a dietary intervention that extends lifespan and healthspan in a variety of organisms. CR improves mitochondrial energy production, fuel oxidation, and reactive oxygen species (ROS) scavenging in skeletal muscle and other tissues, and these processes are thought to be critical to the benefits of CR. PGC-1α is a transcriptional coactivator that regulates mitochondrial function and is induced by CR. Consequently, many of the mitochondrial and metabolic benefits of CR are attributed to increased PGC-1α activity. To test this model, we examined the metabolic and mitochondrial response to CR in mice lacking skeletal muscle . Surprisingly, MKO mice demonstrated a normal improvement in glucose homeostasis in response to CR, indicating that skeletal muscle PGC-1α is dispensable for the wholebody benefits of CR. In contrast, gene expression profiling and electron microscopy (EM) demonstrated that PGC-1α is required for the full CR-induced increases in mitochondrial gene expression and mitochondrial density in skeletal muscle. These results demonstrate that PGC-1α is a major regulator of the mitochondrial response to CR in skeletal muscle, but surprisingly show that neither PGC-1α nor mitochondrial biogenesis in skeletal muscle are required for the whole-body metabolic benefits of CR.

show abstract

Gene expression profiling studies of aging in cardiac and skeletal muscles

Cited by 93 publications

References 69 publications

Defective Myofibroblast Formation from Mesenchymal Stem Cells in the Aging Murine Heart

Defective Myofibroblast Formation from Mesenchymal Stem Cells in the Aging Murine Heart

Induction of premature senescence in cardiomyocytes by doxorubicin as a novel mechanism of myocardial damage

Skeletal muscle transcriptional coactivator PGC-1α mediates mitochondrial, but not metabolic, changes during calorie restriction

Contact Info

Product

Resources

About