Children of the Sun, Children of the Moon—A Mini-Panel for Assessment of Inter-Individual Variation Between the Capacity of Healthy Individuals to Repair Everyday Genotoxic Insults

APOE4, oxidative stress and decreased repair capacity - a no-brainer. Faulty lipid metabolism and increased levels of oxidative damage may be risk factors in the pathogenesis of late-onset dementia

“…Arg72 carriers may have poorer prognosis after ischemic stroke, probably because of increased risk that cells damaged by the excessive production of ROS in the penumbra of the ischemic focus and vulnerable neurons elsewhere in the brain may die in the post-stroke period [161]. At present, there is little published evidence about the role of Pro72Arg polymorphism in the risk for late-onset dementia, except for data about the potential role of the polymorphism in the establishment of risk for cerebrovascular disease and vascular cognitive decline [162,163]. To date, there have been several studies attempting to find an association between the risk for development of sporadic late-onset AD and carriership of allelic variants of TP53, but they have not succeeded in eliciting a link [164,165].…”

“…These include population studies of the potential effects of carriership of allelic variants of genes coding for proteins of repair and maintenance of genomic integrity on the risk for late-onset disease [162,168,169] as well as personalised studies of capacity to repair genotoxic damage and/or the capacity for self-renewal in individually collected cultured cells [170][171][172][173].…”

Individual capacity for DNA repair and maintenance of genomic integrity: a fertile ground for studies in the field of assisted reproduction

“…Not only is it very common (the prevalence of the 72Arg variant allele may reach 80% in some populations), but its two alleles, while being both considered wildtype, may strongly modulate the risk of development of late-onset multifactorial disease, the course of the disease, the potential complications and the outcomes after different treatments (specifically, genotoxic treatments). [39,77] The 72Arg allele confers increased propensity to apoptosis in cells that have sustained genomic damage, whereas the Pro allele may stimulate cell cycle arrest and repair of damage. [78] Genotypes containing at least one 72Arg allele have been repeatedly shown to increase the risk of azoospermia and oligospermia, probably by increasing the rates of apoptosis in developing spermatocytes in a p53-dependent manner.…”

War without Weapons—Constitution of Healthy and Pathological Phenotypes Associated with Polymorphisms in Genes Involved in the Maintenance of Genome Integrity

“…in young and healthy individuals, the presence of the one or the other genotype does not constitute either advantage or disadvantage, except that individuals with the PP genotype may have a slight reproductive disadvantage compared to RR and PR individuals because of a somewhat higher incidence of early embryo implantation failures (20). the P allele is more common in the geographical areas near the equator while the R allele generally becomes more common nearer the poles (64), which is believed by some authors to be related to the dose of environmental genotoxic agents (specifically, UV radiation) regularly received at different latitudes and the presence of other protective factors (14). carriership of the different allelic forms of p53, especially homozygous carriership, however, may play a role of its own in older individuals and/or individuals affected with different conditions.…”