Activation of cardiac progenitor cells reverses the failing heart senescent phenotype and prolongs lifespan

Arantxa Gonzalez, Marcello Rota, Daria Nurzynska, Yu Misao, Jochen Tillmanns, Caroline Ojaimi, M. Elena Padin-Iruegas, Patrick Müller, Grazia Esposito, Claudia Bearzi, Serena Vitale, Buddhadeb Dawn, Santosh K. Sanganalmath, Mathue Baker, Thomas H. Hintze, Roberto Bolli, Konrad Urbanek, Toru Hosoda, Piero Anversa, Jan Kajstura & 1 others Annarosa Leri

Research output: Contribution to journalArticle

Abstract

Heart failure is the leading cause of death in the elderly, but whether this is the result of a primary aging myopathy dictated by depletion of the cardiac progenitor cell (CPC) pool is unknown. Similarly, whether current lifespan reflects the ineluctable genetic clock or heart failure interferes with the genetically determined fate of the organ and organism is an important question. We have identified that chronological age leads to telomeric shortening in CPCs, which by necessity generate a differentiated progeny that rapidly acquires the senescent phenotype conditioning organ aging. CPC aging is mediated by attenuation of the insulin-like growth factor-1/insulin-like growth factor-1 receptor and hepatocyte growth factor/c-Met systems, which do not counteract any longer the CPC renin-angiotensin system, resulting in cellular senescence, growth arrest, and apoptosis. However, pulse-chase 5-bromodeoxyuridine-labeling assay revealed that the senescent heart contains functionally competent CPCs that have the properties of stem cells. This subset of telomerase-competent CPCs have long telomeres and, following activation, migrate to the regions of damage, where they generate a population of young cardiomyocytes, reversing partly the aging myopathy. The senescent heart phenotype and heart failure are corrected to some extent, leading to prolongation of maximum lifespan.

Original languageEnglish (US)
Pages (from-to)597-606
Number of pages10
JournalCirculation Research
Volume102
Issue number5
DOIs
StatePublished - Mar 2008
Externally publishedYes

Fingerprint

Stem Cells
Phenotype
Heart Failure
Cell Aging
Muscular Diseases
Somatomedin Receptors
Hepatocyte Growth Factor
Telomerase
Telomere
Somatomedins
Bromodeoxyuridine
Renin-Angiotensin System
Cardiac Myocytes
Cause of Death
Apoptosis
Growth
Population

Keywords

  • Aging cardiomyopathy
  • Cardiac stem cells
  • Telomere-telomerase system

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Gonzalez, A., Rota, M., Nurzynska, D., Misao, Y., Tillmanns, J., Ojaimi, C., ... Leri, A. (2008). Activation of cardiac progenitor cells reverses the failing heart senescent phenotype and prolongs lifespan. Circulation Research, 102(5), 597-606. https://doi.org/10.1161/CIRCRESAHA.107.165464

Activation of cardiac progenitor cells reverses the failing heart senescent phenotype and prolongs lifespan. / Gonzalez, Arantxa; Rota, Marcello; Nurzynska, Daria; Misao, Yu; Tillmanns, Jochen; Ojaimi, Caroline; Padin-Iruegas, M. Elena; Müller, Patrick; Esposito, Grazia; Bearzi, Claudia; Vitale, Serena; Dawn, Buddhadeb; Sanganalmath, Santosh K.; Baker, Mathue; Hintze, Thomas H.; Bolli, Roberto; Urbanek, Konrad; Hosoda, Toru; Anversa, Piero; Kajstura, Jan; Leri, Annarosa.

In: Circulation Research, Vol. 102, No. 5, 03.2008, p. 597-606.

Research output: Contribution to journalArticle

Gonzalez, A, Rota, M, Nurzynska, D, Misao, Y, Tillmanns, J, Ojaimi, C, Padin-Iruegas, ME, Müller, P, Esposito, G, Bearzi, C, Vitale, S, Dawn, B, Sanganalmath, SK, Baker, M, Hintze, TH, Bolli, R, Urbanek, K, Hosoda, T, Anversa, P, Kajstura, J & Leri, A 2008, 'Activation of cardiac progenitor cells reverses the failing heart senescent phenotype and prolongs lifespan', Circulation Research, vol. 102, no. 5, pp. 597-606. https://doi.org/10.1161/CIRCRESAHA.107.165464
Gonzalez, Arantxa ; Rota, Marcello ; Nurzynska, Daria ; Misao, Yu ; Tillmanns, Jochen ; Ojaimi, Caroline ; Padin-Iruegas, M. Elena ; Müller, Patrick ; Esposito, Grazia ; Bearzi, Claudia ; Vitale, Serena ; Dawn, Buddhadeb ; Sanganalmath, Santosh K. ; Baker, Mathue ; Hintze, Thomas H. ; Bolli, Roberto ; Urbanek, Konrad ; Hosoda, Toru ; Anversa, Piero ; Kajstura, Jan ; Leri, Annarosa. / Activation of cardiac progenitor cells reverses the failing heart senescent phenotype and prolongs lifespan. In: Circulation Research. 2008 ; Vol. 102, No. 5. pp. 597-606.
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AU - Tillmanns, Jochen

AU - Ojaimi, Caroline

AU - Padin-Iruegas, M. Elena

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AU - Bearzi, Claudia

AU - Vitale, Serena

AU - Dawn, Buddhadeb

AU - Sanganalmath, Santosh K.

AU - Baker, Mathue

AU - Hintze, Thomas H.

AU - Bolli, Roberto

AU - Urbanek, Konrad

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