Flies selected for longevity retain a young gene expression profile

Abstract

We investigated correlated responses in the transcriptomes of longevity-selected lines of Drosophila melanogaster to identify pathways that affect life span in metazoan systems. We evaluated the gene expression profile in young, middle-aged, and old male flies, finding that 530 genes were differentially expressed between selected and control flies when measured at the same chronological age. The longevity-selected flies consistently showed expression profiles more similar to control flies one age class younger than control flies of the same age. This finding is in accordance with a younger gene expression profile in longevity-selected lines. Among the genes downregulated in longevity-selected lines, we found a clear over-representation of genes involved in immune functions, supporting the hypothesis of a lifeshortening effect of an overactive immune system, known as inflammaging. We judged the physiological age as the level of cumulative mortality. Eighty-four genes were differentially expressed between the control and longevity-selected lines at the same physiological age, and the overlap between the same chronological and physiological age gene lists included 40 candidate genes for increased longevity. Among these candidates were genes with roles in starvation resistance, immune response regulation, and several that have not yet been linked to longevity. Investigating these genes would provide new knowledge of the pathways that affect life span in invertebrates and, potentially, mammals.

Laboratory selection for increased longevity in Drosophila melanogaster reduces field performance

“…These constraints might be less significant in a laboratory environment with ample food, limited competition and likely fewer incidences of adverse biological interactions. In line with suggestions of laboratory selection leading to correlated responses unlike those expected in nature (Harshman and Hoffmann, 2000;Houle, 1991), lines selected for late life reproduction in our laboratory (Bubliy and Loeschcke, 2005;Sarup et al, 2011) have previously been shown to perform similar, if not superior, in a range of traits when compared to control lines in a standardized laboratory environment (Wit et al, 2013). Others, too, find that lines selected for increased longevity show similar or increased performance in a number of correlated traits (Arking and Wells, 1990;Chippindale et al, 1994Chippindale et al, , 1997Force et al, 1995;Service et al, 1985) The most notable exception to this trend is early life reproduction (Luckinbill et al, 1984;Service, 1989;Zwaan et al, 1995, but see Arking et al, 2002;Leroi et al, 1994a; while developmental time, body size and starvation resistance have occasionally been shown to be negatively affected by selection for increased life span, too (Buck et al, 2000;Force et al, 1995;.…”

Age-Specific Variation in Immune Response inDrosophila melanogasterHas a Genetic Basis

“…The upregulation of Drosophila immunity genes with age is often observed even in the absence of infection (Pletcher et al 2002;Landis et al 2004;Lai et al 2007;Sarup et al 2011) and age-related increases in immune response genes have also been noted in human fibroblast cells (Shelton et al 1999) and mouse brain tissue (Lee et al 2000). The factors responsible for the upregulation of Drosophila immune response genes are not well understood but it has been suggested to result from cumulative exposure to pathogens over time (Ren et al 2007) or the loss in the transcriptional regulation of immune response genes (Zerofsky et al 2005).…”

Nucleotide diversity inflation as a genome-wide response to experimental lifespan extension in Drosophila melanogaster

“…Replicate lines of the control regime were allowed to breed within a week from eclosing and kept under standard laboratory conditions at 25°C and a 12/12 h light/dark cycle on standard agar–sugar–yeast–oatmeal medium. When flies for this experiment were sampled the lines selected for increased longevity had on average a 66% longer median lifespan than control lines in males and 63% in females [70, 71]. Flies from the selection group sampled for sequencing were offspring from an unselected generation, after 48 generations of selection (a total of 107 generations).…”