Abstract
Age is the single greatest risk factor for a wide range of diseases, and as the mean age of human populations grows steadily older, the impact of this risk factor grows as well. Laboratory studies on the basic biology of ageing have shed light on numerous genetic pathways that have strong effects on lifespan. However, we still do not know the degree to which the pathways that affect ageing in the lab also influence variation in rates of ageing and age-related disease in human populations. Similarly, despite considerable effort, we have yet to identify reliable and reproducible 'biomarkers', which are predictors of one's biological as opposed to chronological age. One challenge lies in the enormous mechanistic distance between genotype and downstream ageing phenotypes. Here, we consider the power of studying 'endophenotypes' in the context of ageing. Endophenotypes are the various molecular domains that exist at intermediate levels of organization between the genotype and phenotype. We focus our attention specifically on proteins and metabolites. Proteomic and metabolomic profiling has the potential to help identify the underlying causal mechanisms that link genotype to phenotype. We present a brief review of proteomics and metabolomics in ageing research with a focus on the potential of a systems biology and network-centric perspective in geroscience. While network analyses to study ageing utilizing proteomics and metabolomics are in their infancy, they may be the powerful model needed to discover underlying biological processes that influence natural variation in ageing, age-related disease, and longevity.
Highlights
The earliest molecular genetic studies of ageing focused on understanding individual genes that had significant effects on age-related diseases and longevity
Age is the single greatest risk factor for - myriad = diseases
We present a short review of the potential of proteomic and metabolomic ageing studies, from individual biomarkers of age and age-related disease to metabolic pathway and to network analysis, which we hope will provide a deeper understanding of the biological processes that influence ageing and longevity
Summary
The earliest molecular genetic studies of ageing focused on understanding individual genes that had significant effects on age-related diseases and longevity. By looking at changes in mean levels of proteins and metabolites and in the way that abundances of these molecules correlate with one another in larger networks, we can generate new and potentially powerful hypotheses about ageing and agerelated diseases. We present a short review of the potential of proteomic and metabolomic ageing studies, from individual biomarkers of age and age-related disease to metabolic pathway and to network analysis, which we hope will provide a deeper understanding of the biological processes that influence ageing and longevity.
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