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Correspondence. Preferential amplification of mutant clones as a mechanism of ageing

Correspondence. Preferential amplification of mutant clones as a mechanism of ageing Q J Med 1998; 91:865­866 Correspondence QJM Preferential amplification of mutant clones as a mechanism of ageing Sir, In the ageing human, there is an increased risk of disease and disability. The mechanisms underlying senescent changes are multi-factorial and remain incompletely understood.1 We wish to draw attention to an important but previously neglected phenomenon in ageing: preferential amplification of mutant clones. This process is an inevitable consequence of longevity and affects both dividing cells and highlydifferentiated post-mitotic cells such as neurons and myocytes. We suggest that the intrinsic biological nature of cell differentiation and specialization preordains that preferential amplification of mutant clones will occur progressively with increasing age. There are two major developmental fates for cells in multi-cellular organisms such as the human. Mitotic cells, such as epithelia, experience continual replacement and turnover throughout the lifespan of the organism. There is a tendency for dividing cells to become neoplastic, and cancer involves the preferential expansion of selectively advantaged mutant epithelial clones.2 In evolutionary terms, neoplastic cells undergo natural selection (i.e. tumour progression) to pursue their own reproductive success at the expense of organismal function: this represents one important mechanism of senescence by preferential clonal amplification.3 Post-mitotic tissue, such http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png QJM: An International Journal of Medicine Oxford University Press

Correspondence. Preferential amplification of mutant clones as a mechanism of ageing

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Publisher
Oxford University Press
Copyright
Copyright 1998
ISSN
1460-2725
eISSN
1460-2393
DOI
10.1093/qjmed/91.12.865
Publisher site
See Article on Publisher Site

Abstract

Q J Med 1998; 91:865­866 Correspondence QJM Preferential amplification of mutant clones as a mechanism of ageing Sir, In the ageing human, there is an increased risk of disease and disability. The mechanisms underlying senescent changes are multi-factorial and remain incompletely understood.1 We wish to draw attention to an important but previously neglected phenomenon in ageing: preferential amplification of mutant clones. This process is an inevitable consequence of longevity and affects both dividing cells and highlydifferentiated post-mitotic cells such as neurons and myocytes. We suggest that the intrinsic biological nature of cell differentiation and specialization preordains that preferential amplification of mutant clones will occur progressively with increasing age. There are two major developmental fates for cells in multi-cellular organisms such as the human. Mitotic cells, such as epithelia, experience continual replacement and turnover throughout the lifespan of the organism. There is a tendency for dividing cells to become neoplastic, and cancer involves the preferential expansion of selectively advantaged mutant epithelial clones.2 In evolutionary terms, neoplastic cells undergo natural selection (i.e. tumour progression) to pursue their own reproductive success at the expense of organismal function: this represents one important mechanism of senescence by preferential clonal amplification.3 Post-mitotic tissue, such

Journal

QJM: An International Journal of Medicine – Oxford University Press

Published: Dec 1, 1998

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