Reproduction, fat metabolism, and life span: what is the connection?

Abstract

Reduced reproduction is associated with increased fat storage and prolonged life span in multiple organisms, but the underlying regulatory mechanisms remain poorly understood. Recent studies in several species provide evidence that reproduction, fat metabolism, and longevity are directly coupled. For instance, germline removal in the nematode Caenorhabditis elegans promotes longevity in part by modulating lipid metabolism through effects on fatty acid desaturation, lipolysis, and autophagy. Here, we review these recent studies and discuss the mechanisms by which reproduction modulates fat metabolism and life span. Elucidating the relationship between these processes could contribute to our understanding of age-related diseases including metabolic disorders.

Figure 1. Reproduction, Fat Metabolism, and Lifespan are Intimately Interconnected

Although the mechanistic cause-and-effect relationships are not yet clear, multiple lines of experimental evidence point to tight links between reproduction, fat metabolism, and aging (see bullet points in figure). For example, observations in worms, insects, and rodents indicate that reproduction (top center) can directly affect fat storage and lifespan. Moreover, increased lifespan (bottom right) is often negatively correlated with reproduction and positively correlated with increased fat storage, whereas fat metabolism (bottom left) influences the energetic cost of reproduction and may directly modulate lifespan.

Figure 2. Model of Germline Signaling and Its Impact on Fat Metabolism

Ablation of the germline increases lifespan in C. elegans and D. melanogaster and profoundly alters fat metabolism. To date, our understanding of the underlying molecular mechanisms are mainly based on findings in C. elegans; however, Drosophila homologs are indicated where possible. For functional parallels between steroid signaling in C. elegans and D. melanogaster seeGalikova et al. (2011). Each of the four longevity-promoting transcription factors (DAF-12/EcR, DAF-16/FOXO, PHA-4/FOXA, and NHR-80/HNF4) either target fat remodeling enzymes or activate cellular processes that can affect fat metabolism. Lifespan extension through removal of the germline therefore provides insights into the mechanisms that link reproduction, fat metabolism, and lifespan.