Could future gene therapy prevent aging diseases?

Abstract

BackgroundWithin the next few decades, gene therapy techniques and genetic knowledge may sufficiently advance to support prophylactic gene therapy to prevent polygenic late-onset diseases. A combination of a large number of common low effect gene variants offers the most likely explanation for the heritability of the majority of these diseases, and their risk may be lowered by correcting the effect of a subset of such gene variants.\n\nMethodsComputer simulations quantified the correlation between the aging process, polygenic risk score, and hazard ratio change with age, using as inputs clinical incidence rates and familial heritability, and estimated the outcomes of hypothetical future prophylactic gene therapy on the lifetime risk and age of onset for eight highly prevalent late-onset diseases.\n\nResultsThe simulation results confirmed that gene therapy would be beneficial in both delaying the age of onset and lowering the lifetime risk of the analyzed lateonset diseases. Longer life expectancy is associated with a higher lifetime risk of these diseases, and this tendency, while delayed, will continue after the therapy.\n\nConclusionsWhen the gene therapy as hypothesized here becomes possible, and if the incidences of the treated diseases follow the proportional hazards model with multiplicative genetic architecture composed of a sufficient number of common small effect gene variants, then (a) late-onset diseases with the highest familial heritability will have the largest number of variants available for editing, (b) diseases that currently have the highest lifetime risk, and particularly those with the highest incidence rate continuing into older ages, will prove the most challenging cases in which to lower lifetime risk and delay the age of onset at the populational level, and (c) diseases that are characterized by the lowest lifetime risk will show the strongest and longest-lasting response to such therapy.