Tissue-specificity of gene regulation in aging

A genome-wide study of specific tissues in the fly reveals that different tissues undergo quite different gene regulation changes over the course of aging. From Zhan et al. (in Sige Zou’s lab, where they apparently study gene expression using microarrays sometimes but not others):

Temporal and spatial transcriptional profiles of aging in Drosophila melanogaster

Temporal and tissue-specific alterations in gene expression have profound effects on aging of multicellular organisms. However, much remains unknown about the patterns of molecular changes in different tissues and how different tissues interact with each other during aging. Previous genomic studies on invertebrate aging mostly utilized the whole body or body parts and limited age-points, and failed to address tissue-specific aging. Here we measured genome-wide expression profiles of aging in Drosophila melanogaster for seven tissues representing nervous, muscular, digestive, renal, reproductive, and storage systems at six adult ages. In each tissue, we identified hundreds of age-related genes exhibiting significant changes of transcript levels with age. The age-related genes showed clear tissue-specific patterns: <10% of them in each tissue were in common with any other tissue; <20% of the biological processes enriched with the age-related genes were in common between any two tissues. A significant portion of the age-related genes were those involved in physiological functions regulated by the corresponding tissue. Nevertheless, we identified some overlaps of the age-related functional groups among tissues, suggesting certain common molecular mechanisms that regulate aging in different tissues. This study is one of the first that defined global, temporal, and spatial changes associated with aging from multiple tissues at multiple ages, showing that different tissues age in different patterns in an organism. The spatial and temporal transcriptome data presented in this study provide a basis and a valuable resource for further genetic and genomic investigation of tissue-specific regulation of aging.

I confess that the result comes as not so much of a surprise to me: Different tissues have such starkly different gene expression programs throughout development and adult life that it would only be a shocker if the study had discovered exactly one universal type of age-related change.

Still, I think that the overall lesson — i.e., that tissues age differently — is an important one. It’s clear that each tissue (and, probably, each distinct cell lineage) is subject to its own particular set of constraints, stresses, and requirements for both regeneration and maintenance; hence, “aging,” in a molecular, genomic, or “systems biological” sense, may well be best defined at the tissue/organ level. It’s certainly just as clear (e.g., from the vast literature relating to the daf-2/IGF-1 axis literature) that there are also whole-organism, non-cell-autonomous phenomena at play. Nonetheless, organ-specific aging is likely to be very significant from the standpoint of age-related change and decline in tissue function — so it is well and good that it be studied and cataloged.