Tags

Type your tag names separated by a space and hit enter

Cardiac stem cell and myocyte aging, heart failure, and insulin-like growth factor-1 overexpression.
Circ Res. 2004 Mar 05; 94(4):514-24.CircR

Abstract

To determine whether cellular aging leads to a cardiomyopathy and heart failure, markers of cellular senescence, cell death, telomerase activity, telomere integrity, and cell regeneration were measured in myocytes of aging wild-type mice (WT). These parameters were similarly studied in insulin-like growth factor-1 (IGF-1) transgenic mice (TG) because IGF-1 promotes cell growth and survival and may delay cellular aging. Importantly, the consequences of aging on cardiac stem cell (CSC) growth and senescence were evaluated. Gene products implicated in growth arrest and senescence, such as p27Kip1, p53, p16INK4a, and p19ARF, were detected in myocytes of young WT mice, and their expression increased with age. IGF-1 attenuated the levels of these proteins at all ages. Telomerase activity decreased in aging WT myocytes but increased in TG, paralleling the changes in Akt phosphorylation. Reduction in nuclear phospho-Akt and telomerase resulted in telomere shortening and uncapping in WT myocytes. Senescence and death of CSCs increased with age in WT impairing the growth and turnover of cells in the heart. DNA damage and myocyte death exceeded cell formation in old WT, leading to a decreased number of myocytes and heart failure. This did not occur in TG in which CSC-mediated myocyte regeneration compensated for the extent of cell death preventing ventricular dysfunction. IGF-1 enhanced nuclear phospho-Akt and telomerase delaying cellular aging and death. The differential response of TG mice to chronological age may result from preservation of functional CSCs undergoing myocyte commitment. In conclusion, senescence of CSCs and myocytes conditions the development of an aging myopathy.

Authors+Show Affiliations

Cardiovascular Research Institute, Department of Medicine, New York Medical College, Valhalla, NY 10595, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14726476

Citation

Torella, Daniele, et al. "Cardiac Stem Cell and Myocyte Aging, Heart Failure, and Insulin-like Growth Factor-1 Overexpression." Circulation Research, vol. 94, no. 4, 2004, pp. 514-24.
Torella D, Rota M, Nurzynska D, et al. Cardiac stem cell and myocyte aging, heart failure, and insulin-like growth factor-1 overexpression. Circ Res. 2004;94(4):514-24.
Torella, D., Rota, M., Nurzynska, D., Musso, E., Monsen, A., Shiraishi, I., Zias, E., Walsh, K., Rosenzweig, A., Sussman, M. A., Urbanek, K., Nadal-Ginard, B., Kajstura, J., Anversa, P., & Leri, A. (2004). Cardiac stem cell and myocyte aging, heart failure, and insulin-like growth factor-1 overexpression. Circulation Research, 94(4), 514-24.
Torella D, et al. Cardiac Stem Cell and Myocyte Aging, Heart Failure, and Insulin-like Growth Factor-1 Overexpression. Circ Res. 2004 Mar 5;94(4):514-24. PubMed PMID: 14726476.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cardiac stem cell and myocyte aging, heart failure, and insulin-like growth factor-1 overexpression. AU - Torella,Daniele, AU - Rota,Marcello, AU - Nurzynska,Daria, AU - Musso,Ezio, AU - Monsen,Alyssa, AU - Shiraishi,Isao, AU - Zias,Elias, AU - Walsh,Kenneth, AU - Rosenzweig,Anthony, AU - Sussman,Mark A, AU - Urbanek,Konrad, AU - Nadal-Ginard,Bernardo, AU - Kajstura,Jan, AU - Anversa,Piero, AU - Leri,Annarosa, Y1 - 2004/01/15/ PY - 2004/1/17/pubmed PY - 2004/5/22/medline PY - 2004/1/17/entrez SP - 514 EP - 24 JF - Circulation research JO - Circ Res VL - 94 IS - 4 N2 - To determine whether cellular aging leads to a cardiomyopathy and heart failure, markers of cellular senescence, cell death, telomerase activity, telomere integrity, and cell regeneration were measured in myocytes of aging wild-type mice (WT). These parameters were similarly studied in insulin-like growth factor-1 (IGF-1) transgenic mice (TG) because IGF-1 promotes cell growth and survival and may delay cellular aging. Importantly, the consequences of aging on cardiac stem cell (CSC) growth and senescence were evaluated. Gene products implicated in growth arrest and senescence, such as p27Kip1, p53, p16INK4a, and p19ARF, were detected in myocytes of young WT mice, and their expression increased with age. IGF-1 attenuated the levels of these proteins at all ages. Telomerase activity decreased in aging WT myocytes but increased in TG, paralleling the changes in Akt phosphorylation. Reduction in nuclear phospho-Akt and telomerase resulted in telomere shortening and uncapping in WT myocytes. Senescence and death of CSCs increased with age in WT impairing the growth and turnover of cells in the heart. DNA damage and myocyte death exceeded cell formation in old WT, leading to a decreased number of myocytes and heart failure. This did not occur in TG in which CSC-mediated myocyte regeneration compensated for the extent of cell death preventing ventricular dysfunction. IGF-1 enhanced nuclear phospho-Akt and telomerase delaying cellular aging and death. The differential response of TG mice to chronological age may result from preservation of functional CSCs undergoing myocyte commitment. In conclusion, senescence of CSCs and myocytes conditions the development of an aging myopathy. SN - 1524-4571 UR - https://www.unboundmedicine.com/medline/citation/14726476/Cardiac_stem_cell_and_myocyte_aging_heart_failure_and_insulin_like_growth_factor_1_overexpression_ L2 - https://www.ahajournals.org/doi/10.1161/01.RES.0000117306.10142.50?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -