Phenome and genome based studies into human ageing and longevity: An overview

Abstract

Human ageing is an extremely personal process leading across the life course of individuals to large population heterogeneity in the decline of functional capacity, health and lifespan. The extremes of this process are witnessed by the healthy vital 100-year-olds on one end and the 60-year-olds suffering from multiple morbid conditions on the other end of the spectrum. Molecular studies into the basis of this heterogeneity have focused on a range of endpoints and methodological approaches. The phenotype definitions most prominently investigated in these studies are either lifespan-related or biomarker based indices of the biological ageing rate of individuals and their tissues. Unlike for many complex, age-related diseases, consensus on the ultimate set of multi-biomarker ageing or lifespan-related phenotypes for genetic and genomic studies has not been reached yet. Comparable to animal models, hallmarks of age-related disease risk, healthy ageing and longevity include immune and metabolic pathways. Potentially novel genomic regions and pathways have been identified among many (epi)genomic studies into chronological age and studies into human lifespan regulation, with APOE and FOXO3A representing yet the most robust loci. Functional analysis of a handful of genes in cell-based and animal models is ongoing. The way forward in human ageing and longevity studies seems through improvements in the interpretation of the biology of the genome, in application of computational and systems biology, integration with animal models and by harmonization of repeated phenotypic and omics measures in longitudinal and intervention studies. This article is part of a Special Issue entitled: Model Systems of Aging - edited by "Houtkooper Riekelt".

Keywords: Ageing; Biomarker; Genome; Human; Longevity; Molecular.