Biomaterial Database

Genetic and epigenetic mechanisms for the limited lifespan and ageing of normal, diploid cells. 1993

Z Srebro

Department of Embryology and Medical Genetics, Jagellonian University Medical College, Kraków.

The genetic basis of the limited lifespan and apparently programmed number of divisions in normal, diploid cells is discussed. Two different mechanisms may underlie a programmed inhibition of cell divisions before they age and die: 1. A genetic mechanism involving the CpG sequence in promotor regions of genes. Inactive, but gradually activated basic function genes such as ribosomal and energy metabolism genes, when inactive have their CpG promotor sequences methylated. During each cell division a proportion of 5-methyl cytosines will be oxidatively deaminated leading to C to T transitions. After a certain number of divisions all methylated CpG islands will be mutated with consequent loss of viability and cell death. 2. An epigenetic mechanism involving the methylated promotor sequences of silent growth control genes. After a certain number of divisions with incomplete maintenance methylation, the growth control genes will be derepressed with consequent cessation of proliferation, decline of metabolic activity, ageing, and death.

UI	MeSH Term	Description	Entries
D008745	Methylation	Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. (From Stedman, 25th ed)	Methylations
D008938	Mitosis	A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.	M Phase, Mitotic,Mitotic M Phase,M Phases, Mitotic,Mitoses,Mitotic M Phases,Phase, Mitotic M,Phases, Mitotic M
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D012016	Reference Values	The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality.	Normal Range,Normal Values,Reference Ranges,Normal Ranges,Normal Value,Range, Normal,Range, Reference,Ranges, Normal,Ranges, Reference,Reference Range,Reference Value,Value, Normal,Value, Reference,Values, Normal,Values, Reference
D002468	Cell Physiological Phenomena	Cellular processes, properties, and characteristics.	Cell Physiological Processes,Cell Physiology,Cell Physiological Phenomenon,Cell Physiological Process,Physiology, Cell,Phenomena, Cell Physiological,Phenomenon, Cell Physiological,Physiological Process, Cell,Physiological Processes, Cell,Process, Cell Physiological,Processes, Cell Physiological
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D004171	Diploidy	The chromosomal constitution of cells, in which each type of CHROMOSOME is represented twice. Symbol: 2N or 2X.	Diploid,Diploid Cell,Cell, Diploid,Cells, Diploid,Diploid Cells,Diploidies,Diploids
D004260	DNA Repair	The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones.	DNA Damage Response
D005347	Fibroblasts	Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.	Fibroblast
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man