Abstract
Steroids are essential structural components of cell membranes that organize lipid rafts and modulate membrane fluidity. They can also act as signalling molecules that work through nuclear and G protein–coupled receptors to impact health and disease. Notably, changes in steroid levels have been implicated in metabolic, cardiovascular and neurodegenerative diseases, but how alterations in the steroid pool affect ageing is less well understood. One of the major challenges in steroidomic analysis is the ability to simultaneously detect and distinguish various steroids due to low in vivo concentrations and naturally occurring stereoisomers. Here, we established such a method to study the mass spectrometry behaviour of nine sterols/steroids and related molecules (cholesterol precursors: squalene, lanosterol; sterol metabolites; 7 Dehydrocholesterol, 24, 25 and 27 Hydroxycholesterol; and steroids: progesterone, testosterone, and corticosterone) during ageing in the African turquoise killifish, a new model for studying vertebrate longevity. We find that levels of all tested steroids change significantly with age in multiple tissues, suggesting that specific steroids could be used as biomarkers of ageing. These findings pave the way for use of Nothobranchius furzeri as a novel model organism to unravel the role of sterols/steroids in ageing and age-related diseases.Graphical abstract
Highlights
Sterols and steroids are essential heterocyclic molecules used by all metazoans for diverse biological processes
To narrow down the crucial settings to maximize the sensitivity for the quantification of steroid in killifish samples, we explored several mass spectrometry parameters using steroid standards (100 ng)
We report the mean intensity for each standard in the figures, whereas the corresponding relative standard deviations (RSD) are reported in Electronic Supplementary Material (ESM) Tables (S1-S7)
Summary
Sterols and steroids are essential heterocyclic molecules used by all metazoans for diverse biological processes. They are important structural components of cell membranes that comprise lipid rafts and decrease membrane fluidity [1]. The most abundant sterol is cholesterol, which is salvaged from the diet or de novo synthesized through a series of steps. Cholesterol can undergo several modifications and transmutation reactions leading to a plethora of sterol/steroid-like molecules with different biological functions including oxysterols, bile acids, steroids, corticoids, and secosteroids [4]
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