Nematodes that lack sex cells accumulate fat. Image credit: Steinbaugh et al (2015) (CC BY 4.0)

A key to longevity

Misplaced fat causes stress responses that increase the lifespans of worms that lack sex cells.

Understanding how animals age may help us to prevent age-related or chronic diseases, such as type 2 diabetes and cancer. The tiny nematode worm known as C. elegans is widely used as a model to study aging and has enabled researchers to identify factors that can slow down the aging process. Like other animals, these worms contain female and male sex cells that originate from cells called germline stem cells. The normal lifespan of C. elegans is less than three weeks, but when the germline stem cells are removed, the worms can live for much longer.

Reproduction requires a lot of energy, which is typically ‘stored’ in molecules of fat. Animals utilize their fat reserves and release this energy by breaking the fat molecules down into smaller molecules as part of their ‘metabolism’. Worms that have had their germline stem cells removed have altered fat metabolism, and it is thought that this may contribute to their increased lifespan. These worms have increased levels of a protein called SKN-1, which alters fat metabolism and helps to protect cells from toxic molecules and other stresses.

SKN-1 works by regulating the activity (or ‘expression’) of many genes in cells, but it is not clear how this increases the lifespan of the worms. Michael Steinbaugh and colleagues studied mutant worms that were lacking SKN-1. Unlike normal worms, when the germline stem cells were removed from the mutants, their lifespan did not increase. Further experiments analyzed the genes that are switched on by SKN-1, and identified many that are involved in fat metabolism, in degrading other proteins, and in detoxifying harmful molecules. The experiments also found that SKN-1 reduces the overall amount of fat stored in the body.

Next, Steinbaugh and colleagues investigated how SKN-1 stops fat from being stored. During reproduction, cells in the gut produce yolk — which is rich in fats — that will be provided to germ cells to nourish the developing embryo. Worms lacking germline stem cells are not able to reproduce, but they continue to make yolk. Steinbaugh and colleagues found that the build up of the yolk activates SKN-1, which in turn inhibits the further accumulation of fats.

Steinbaugh and colleagues’ findings show that SKN-1 can be activated by fat molecules and plays a direct role in controlling the amount of fat stored in the body of the worms. A future challenge will be to identify the specific fat molecules that activate SKN-1, which could provide a model for understanding how specific fats in human diets could have wide-ranging health benefits.

To find out more

Read the eLife research paper on which this eLife digest is based: “Lipid-mediated regulation of SKN-1/Nrf in response to germ cell absence” (July 21, 2015).
Read a commentary on this research paper: “Aging: Stressing about misplaced fat is a key to longevity”.
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