Keynote lecture: The genetics and epigenetics of altered proliferative homeostasis in ageing and cancer

摘要

Ageing mammals are subject to an amazing array of aberrations in proliferative homeostasis. These are of two basic types: the post-maturational failure to adequately replace effete somatic cells (atrophies) and excessive proliferations of somatic cells (hyperplasias). To a surprising degree, these occur side by side within the same tissues and are features of numerous mammalian geriatric disorders. Atrophy is the likely usual initial event, the proliferative response perhaps developing as a secondary, compensatory, initially adaptive reaction. We have little understanding of why this putative compensatory reaction so often fails to be appropriately regulated in ageing mammals, leading to such pathologies as chronic inflammation, fibrosis, metaplasia and neoplasia. Advances in formal genetic analysis, mutagenesis, stem cell biology and epigenetics are likely to provide major new understanding. Stochastic epigenetic shifts in gene expression are of growing interest, particularly in explaining intra-specific variations on rates and patterns of ageing. Nature may well have evolved such random fluctuations in gene expression as a type of group-selectionist adaptive strategy to cope with diverse stochastic environmental challenges. Alternatively, such background “noise” in transcription and translation may simply reflect a type of informational entropy.