Differential Genetic Advantages in Youth and in Aging, or How to Die Healthy

Khalil, Hilal S.; Petkova, Rumena; Zhelev, Nikolai

doi:10.5504/bbeq.2011.0151

Cited by 8 publications

(10 citation statements)

References 87 publications

(71 reference statements)

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“…It soon became clear that the strength of the associations of these polymorphisms with human diseases and conditions may be very different in different populations, and in individuals at different ages. While the former could among other things, reflect population-specific intra-genomic interferences between alternative alleles at different loci, the latter was less straightforward and was attributed by some authors to the phenomenon of 'antagonistic pleiotropy', that is the case of one genetic trait being beneficial at early age but deleterious at a later age or vice versa (Khalil et al 2012a, Chakarov et al 2014a). There was one notable case in which the same allele of a single-nucleotide polymorphism (ERCC1 C8092A) was associated with opposite effects on the survival of patients with the same disease treated with the same type of agents in two independent large studies (Zhou 2004, Kalikaki et al 2009).…”

Section: Methodologies Of Irc Assessment -Typing Polymorphisms May Nomentioning

confidence: 99%

The success of stem cell transplantations and the potential post-transplantation complications may be dependent, among other factors, on the capacity of the recipient and the transplanted cells to repair DNA damage

Reynolds¹

2016

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Cell therapy is presently a treatment of choice for many types of haematological and metabolic diseases and is likely to become a therapeutic option for other severe human diseases and conditions in the near future. The success of cell transplantation depends on a variety of factors, including the degree of HLA match between the donor and the recipient, the infectious burden of the graft, cell dosage, age, general state of the recipient and other incompletely characterised features of the donor and the recipient. It is likely that the individual capacity for identification and repair of DNA damage and maintenance of genomic integrity may account, at least in part, for these elusive factors that modulate transplantation outcome in terms of success rate and both long and short term posttransplantation complications. This paper outlines the role of individual repair capacity of the donor and recipient in cell transplantations, summarising the little knowledge already accumulated in the field whilst analysing the known major issues of the use of different types of stem cells. Attention will be given to their capacity to maintain the integrity of their genome, the ability to renew their own population, differentiate into various cell types and in ‡

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Section: Methodologies Of Irc Assessment -Typing Polymorphisms May Nomentioning

confidence: 99%

The success of stem cell transplantations and the potential post-transplantation complications may be dependent, among other factors, on the capacity of the recipient and the transplanted cells to repair DNA damage

Reynolds¹

2016

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“…At the same time, carriership of the variant allele of the rs929271 LIF polymorphism was reported to be associated with increased ongoing pregnancy rates after IVF [93]. Apparently, carriership of this polymorphic allele may be associated with adverse effects on female fertility in young age and a beneficial effect at later age and/or after IVF, that is, it may represent an example of antagonistic pleiotropy [94].…”

Section: Reproductive Outcomes and Individual Repair Capacitymentioning

confidence: 99%

Reproductive outcomes in pregnant women aged 35 or older: the role of individual repair capacity

Petkova¹,

Dimitrova²,

Zhelev³

et al. 2015

Biodiscovery

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Abbreviations: 8-OH-dG -8-hydroxydeoxyguanosine, AMA -advanced maternal age, AR -assisted reproduction, BER -base excision repair, CDC -US Centre for disease prevention and control, DIC -disseminated intravascular coagulation, DS -Down syndrome, HELLP -haemolysis/elevated liver enzymes/low platelets, ICSI -intracytoplasmic sperm injection, IRC -individual repair capacity, IUGR -intrauterine growth restriction, IUI -intrauterine insemination, IVF -in vitro fertilisation, LIF -leukaemia inhibitory factor, NER -nucleotide excision repair, PCOS -polycystic ovary syndrome, PIH -pregnancy-induced hypertension, ROS -reactive oxygen species, TTD -trichothiodystrophy, w.g. -weeks of gestation, WHO -World Health Organisation, XP -xeroderma pigmentosum. AbstractAt present, childbirth is being progressively postponed until later age. Women aged 35 or older may have to wait longer to conceive than younger women and are more likely to be referred to fertility evaluations, but in a significant proportion a spontaneous conception would be achieved in the timeframe typical of younger women. Pregnancies where mothers are ≥ 35 are associated with more risks for pregnancy loss, chromosomal disease, pregnancy-associated complications, prematurity and low birthweight. These concerns, however, are not uncommon in younger women as well. This puts forward the question whether advanced age per se is the underlying cause for the increased risk for adverse outcomes in older pregnant women, or whether there might be other factors that account for it but do not radically worsen the prospects for favourable outcomes. The individual risks associated with childbirth late in life may stem from maternal genetic background rather than being a simple function of age. There is plenty of preliminary evidence that individual capacity for identification and repair of DNA damage may constitute a major factor in female fertility and fecundity. Subtle deficiencies in the repair capacity may have little to no importance in younger pregnant women but may make a significant difference in older women. The outcomes of pregnancies in women >35 are largely dependent on the prepregnancy health status and the quality of antenatal care, and may not be dramatically different from outcomes in younger women.

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“…it has been demonstrated, however, that individuals with homozygous R/R genotypes may have poorer outcomes after incidents of acute ischaemia, which is most likely related to the proneness of damaged R/R cells to apoptosis compared to cells with P/R and P/P genotypes (1,25). Apparently, the process of physiological aging as well as the process of development of disease may serve as tipping points in the balance between the pro-transactivation and the pro-apoptotic properties of p53, with consequences dependent on the combined impact of other factors (35,72).…”

Section: P53mentioning

confidence: 99%

“…it has been shown in murine models, however, that constitutively high levels of the non-cancerous isoforms of p53 are associated with a striking phenotype of premature aging (24). it is believed that the aging is a major anticancer mechanism that p53 deploys in order to ensure that cells at high risk of significant alterations in their DnA are systematically and safely removed from the replicative pool (10,35,57).…”

Section: P53mentioning

confidence: 99%

“…Mass apoptosis of selected cell populations is a hallmark of the pathogenesis of some of the common severe consequences of uncontrolled hyperglycemia -accelerated vascular aging, retinopathy, neuropathy, etc. it could be hypothesized that the presence of the pro-apoptotic form of p53 in cells which are already under increased levels of genotoxic stress for any reason, may serve well when the organism is young, but not that well as the organism ages, possibly as an expression of the phenomenon of antagonistic pleiotropy (35). More specifically, in case that the underlying hyperglycemic state is poorly managed, the pro-apoptotic p53 may handle the ongoing avalanche of genotoxic damage at young age by routing cells with potential for oncogenic transformation to the programmed cell death pathway.…”

Section: Role Of Mutations In Genes Not Related Directly To Dna Repaimentioning

confidence: 99%

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

Oluwaseun

Khalil

2012

Biotechnology & Biotechnological Equipment

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Differential Genetic Advantages in Youth and in Aging, or How to Die Healthy

Cited by 8 publications

References 87 publications

The success of stem cell transplantations and the potential post-transplantation complications may be dependent, among other factors, on the capacity of the recipient and the transplanted cells to repair DNA damage

The success of stem cell transplantations and the potential post-transplantation complications may be dependent, among other factors, on the capacity of the recipient and the transplanted cells to repair DNA damage

Reproductive outcomes in pregnant women aged 35 or older: the role of individual repair capacity

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

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