Complex diseases are major contributors to human mortality in old age. Paradoxically, many genetic variants that have been associated with increased risks of such diseases are found in genomes of long-lived people, and do not seem to compromise longevity. Here we argue that trade-off-like and conditional effects of genes can play central role in this phenomenon and in determining longevity. Such effects may occur as result of: (i) antagonistic influence of gene on the development of different health disorders; (ii) change in effect of gene on vulnerability to death with age (especially, from “bad” to “good”); (iii) gene-gene interaction; and (iv) gene-environment interaction, among other factors. Review of current knowledge provides many examples of genetic factors that may favor the risk of one disease but reduce chances of developing another serious health condition, or improve survival from it. Factors that may increase risk of a major disease but attenuate manifestation of physical senescence are also discussed. Overall, available evidence suggests that influence of a genetic variant on longevity may be negative, neutral or positive, depending on a delicate balance of the detrimental and beneficial effects of such variant on multiple health and aging related traits. This balance may change with age, internal and external environments, and depend on genetic surrounding. We conclude that trade-off-like and conditional genetic effects are very common and may result in situations when a disease “risk allele” can also be a pro-longevity variant, depending on context. We emphasize importance of considering such effects in both aging research and disease prevention.

BackgroundThere is no mechanism that matches hard-to-place kidneys with the most appropriate candidate. Thus, unwanted kidney offers are typically to recipients with long renal replacement time (vintage) which is a strong risk factor for mortality and graft failure, and in combination with prolonged cold ischemia time (CIT), may promote interactive effects on outcomes.MethodsConsecutive adult isolated kidney transplants between October 2015 and December 2017 were stratified by vintage younger than 1 year and CIT longer than 30 hours.ResultsLong (n = 169) relative to short (n = 93) vintage recipients were significantly more likely to be younger (32.2 years vs 56.9 years, P = 0.02), black race (40.8% vs 18.3%, P = 0.02), have higher estimated posttransplant survival (52.6 vs 42.0, P = 0.04), and have a comorbid condition (45.6% vs 30.1%, P = 0.02); they were less likely to receive a donation after circulatory death kidney (27.8% vs 39.8%, P = 0.05). Long vintage was significantly associated with length of stay longer than 4 days (45.5% vs 30.1%, P = 0.02), and 30-day readmission (37.3% vs 22.6%, P = 0.02) but not additional operations (17.8% vs 15.1%, P = 0.58), short-term patient mortality (3.0% vs 2.2%, P = 0.70), or overall graft survival (P = 0.23). On multivariate logistic regression, long vintage remained an independent risk factor for 30-day readmission (adjusted odds ratio, 1.92; 95% confidence interval, 1.06-3.47); however, there was no interaction of vintage and CIT for this outcome (P = 0.84).ConclusionsReadmission is significantly associated with pretransplant dialysis duration; however, CIT is not a modifying factor for this outcome.

No abstract

Their hierarchical manifestation provided five basic elements (Pancha-Mahabhutas = PM) namely Earth (Pruthvi), Water (Jala), Fire (Agni), Air (Vayu) and Space (Akash)-their relationships are shown in Fig.2.1. The PMare not discrete entities but have a continuum of Entropy and Enthalpy.

No abstract