Cellular and molecular determinants of ageing.

The highly complex nature of the process of ageing implicates both genetic and epigenetic causative factors. A progressive failure of maintenance underlines and typifies this process. The instability of the nuclear and the mitochondrial genomes is an important determinant of ageing. Infidelity and misregulation of genetic information transfer, loss of cellular proliferative capacity, altered cellular responsiveness and defective pathways of signal transduction are major aspects of the failure of homeostasis. These are also the basis of age-related diseases and impairments, such as osteoporosis, arthritis, immune deficiency, altered drug clearance and altered functioning of the brain. Studies directed towards understanding the mechanisms of interaction and inter-dependence of various genes involved in maintenance and repair networks are the most promising research strategies for identifying gerontogenes.