| Abstract: | Aging is defined as loss of homeostasis which affects all metabolic systems, including DNA. Interspecies comparisons and lessons from the human genetic instability syndromes suggest a correlation between DNA-homeostasis and maximum lifespan, whereas average lifespan depends mainly on environmental factors. Current demographic data suggest a maximum lifespan in humans of 110–115. The average life expectancy at birth has reached 80 years in the wealthy nations and may exceed, at least in females, 90 years by the year 2050. Genetic and biological reasons, but also lifestyle factors, account for the greater longevity of women. Attempt to define a ?longevity“ genotype so far have not been met with success, but carriers of the ApoE4-Allele appear to have a disadvantage. Unlike the situation in model organisms, aging and longevity in humans seem to be influenced by numerous genes and environmental interactions. Most people do not die of old age but of age-related diseases which are frequent because of lack of natural selection against genetic defects that cause late-onset diseases. Moreover, genes causing late-onset diseases show evidence of antagonistic pleiotropy, rendering these genes resistant to removal from our genome. Likewise, thermoinstability of DNA and generation of reactive oxygen species during oxidative phosphorylation are two endogenous sources of genomic instability that limit our lifespan and cannot be overcome without fundamentally altering the biological make-up of our species. Genomic instability causes cancer and accelerates the aging process, as evidenced by the human caretaker gene syndromes which typically show progeroid features. From a genetic point of view, cancer and aging may be moderately delayed and / or mitigated by lifestyle and medical / environmental interventions, but given the constraints of our biological make-up, they cannot be eradicated. |
