Molecular basis of aging

Recent developments and emerging notions imply a strict genetic control of aging-associated processes. Life span seems to be controlled on three levels. On an organismic level key genes have been identified in the yeast. Caenorhabditis elegans and mouse such as SIR 1-4, DAF-2, 23 and KLOTHO that are believed to super-impose a broad spectrum of gene activities relevant to lifespan. Mutations with loss of activity lead to pretermed senescence in young individuals those with gain of function ensue in Prolonged life expectancy. Aging is also regulated on a clonal level as progenies emerge from stem cells. Telomerase competence maintain their ability of self renewal. In proliferating progenies up-regulation of telomerase provides the ground for the asymmetrical proliferation of differentiating descendants within strict limits and in a pre-destined number The mechanism of this second control level as been well clarified in the meantime and attributed to the proliferation-associated attrition of the flanking DNA tandem-repeats of the chromosomes termed telomeres. Whereas germ cells, somatic and fetal stem cells as well as cancer cells are telomerase competent and can up-regulate the gene for this telomere reverse transcriptase on peripheral demand, somatic cells lack this capability. With few negligible possible exceptions, the overwhelming majority of spontaneous cancers seems to share the common feature. of telomerase expression. On a cellular level, the life expectancy is regulated by the cell cycle-associated events, deciding on cycle-arrest and apoptosis or oil optional transit from the G0-quiescence into G1 or senescence.