| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1906887 | Experimental Gerontology | 2011 | 11 Pages |
Apolipoprotein D (ApoD), a member of the Lipocalin family, is the gene most up-regulated with age in the mammalian brain. Its expression strongly correlates with aging-associated neurodegenerative and metabolic diseases. Two homologues of ApoD expressed in the Drosophila brain, Glial Lazarillo (GLaz) and Neural Lazarillo (NLaz), are known to alter longevity in male flies. However, sex differences in the aging process have not been explored so far for these genes. Here we demonstrate that NLaz alters lifespan in both sexes, but unexpectedly the lack of GLaz influences longevity in a sex-specific way, reducing longevity in males but not in females. While NLaz has metabolic functions similar to ApoD, the regulation of GLaz expression upon aging is the closest to ApoD in the aging brain. A multivariate analysis of physiological parameters relevant to lifespan modulation uncovers both common and specialized functions for the two Lipocalins, and reveals that changes in protein homeostasis account for the observed sex-specific patterns of longevity. The response to oxidative stress and accumulation of lipid peroxides are among their common functions, while the transcriptional and behavioral response to starvation, the pattern of daily locomotor activity, storage of fat along aging, fertility, and courtship behavior differentiate NLaz from GLaz mutants. We also demonstrate that food composition is an important environmental parameter influencing stress resistance and reproductive phenotypes of both Lipocalin mutants. Since ApoD shares many properties with the common ancestor of invertebrate Lipocalins, we must benefit from this global comparison with both GLaz and NLaz to understand the complex functions of ApoD in mammalian aging and neurodegeneration.
Graphical AbstractFigure optionsDownload full-size imageDownload as PowerPoint slideResearch highlights► The Lipocalins GLaz and NLaz alter longevity in a sex-specific manner. ► Like ApoD, GLaz increases its expression in the aged brain, but only in females. ► A multivariate analysis reveals specialized and redundant Lipocalin functions. ► Response to oxidative stress and control of lipid peroxidation are common functions. ► NLaz and GLaz alter metabolism and reproduction in different and complementary ways.
