Published online before print May 26, 2008, doi: 10.1161/HYPERTENSIONAHA.107.108563
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(Hypertension. 2008;52:61.)
© 2008 American Heart Association, Inc.
Editorial Commentaries |
Treatment-Sensitive Premature Renal and Heart Senescence in Hypertension
From the Department of Cardiology (M.W.B., C.G.), Franz Volhard Clinic, Charité Campus Buch and HELIOS Kliniken Berlin, Berlin, Germany; Max Delbrück Center for Molecular Medicine (L.Z.), Berlin, Germany
Correspondence to Martin W. Bergmann, Department of Cardiology, Franz Volhard Clinic, Charité Campus Buch, Schwanebecker Chaussee 50, 13125 Berlin, Germany. E-mail martin.bergmann@charite.de
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Hypertension-induced renal and heart failure account for a large proportion of chronic disease burden in the elderly. Antihypertensive therapy may halt the progression of disease. Preventing organ damage has emerged as a primary target for new approaches to treat hypertension. Signaling pathways affected by hypertension but not necessarily involved in blood pressure regulation itself have been identified as attractive new targets.
Already in the early 1960s, a cellular stopwatch was described, which induced a growth arrest of normal somatic cells after several rounds of cell division in culture. In contrast, cancer cells were found to proliferate unlimited, implicating cellular senescence as an important molecular mechanism of protection against cancer. The molecular and cellular pathways controlling senescence have since been identified. The 3 "Hayflick factors" recording the proliferative history of cells and tissues are telomere shortening, accumulation of damaged DNA plus chromosomal damage, as well as derepression of the INK4a/ARF genomic locus. The molecular pathways mediating senescence, namely, telomere shortening and expression of p16INK4a through stress and aberrant signaling–induced senescence are dissociated, indicating independent pathways.1
On a cellular level, a picture is emerging that tissue senescence is not only about the differentiated cells having a limited life span but also, and possibly even more important, reduced regenerative capacity of organ-resident stem cells.2 Although telomere shortening records cell division and finally leads to activation of the p53 pathway inducing apoptosis, the cell-cycle inhibitor p16INK4a may directly affect regenerative and proliferative activity of organ-resident stem cells because of inhibition of cyclin-dependent kinases 4
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