Temporal and spatial transcriptional profiles of aging in Drosophila melanogaster

Abstract

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.

Figure 1.

Fly tissues for microarray experiments. (A) RNA samples for microarray experiments were prepared from seven tissues shown in the fly image. (B) Lifespan curve of w¹¹¹⁸. The mean lifespan of w¹¹¹⁸ at 25°C was 59.2 ± 2.3 d. The age-points labeled on the curve represent ages of males when tissues were collected for microarray experiments.

Figure 2.

Heat map presentation of expression patterns of the age-related genes in each tissue. (A) Brain; (B) muscle; (C) gut; (D) MT; (E) Acg; (F) testis; (G) adipose tissue. Each column represents an age-point. Each row represents the expression pattern of one gene across all the age-points. The ratios of transcript levels between experiment and reference samples are color-coded in red and green. Red represents an increase of the transcript level of a gene in the experiment samples aged 15–60 d compared with the 3-d-old reference sample, and green represents a decrease. The age-related genes in each tissue are grouped to three to eight clusters (labeled as C1 to C8) by hierarchical clustering analysis based on their similarities in expressional profiles.

Figure 3.

PCA maps were generated with the age-related genes showing relationships of transcriptional profiles of aging among different tissues. The amount of variation covered by the top three principle components are as follows: (#1) 8.71%; (#2) 7.91%; (#3) 5.12%. The samples of seven tissues are color-coded. Each small sphere represents projection of one age sample from one tissue in the three-dimensional space formed by the top three principle components. Each large oval represents the area covered by all the samples of one tissue formed by the small spheres.

Figure 4.

Hierarchical clustering analysis of temporal transcriptional profiles of individual tissues using the age-related genes. In each tissue, the difference of transcriptomic data at different ages is reflected by the distance scale bar shown at the bottom of each cluster dendrogram. Each branch represents one age-point labeled in the order of age, tissue type, and data set identification. (A) Gut; (B) brain; (C) testis; (D) Acg; (E) muscle; (F) fat; (G) MT.