A new study from Michigan State University researchers further supports the "obesity paradox," showing that cells with higher fat contents outlive lean cells. The results have implications for larger organisms, including humans, and support the current data showing that overweight people have the lowest-all cause mortality rates, while fit people have higher mortality rates that are similar to those seen in people labeled as slightly obese.
"The obesity paradox baffles scientists across numerous disciplines," Min-Hao Kuo, lead author of the study, said in a press release. "But when it comes to yeast, which is an excellent model for the studies of human aging, increasing the cellular content of triacylglycerol, or fat, extends the lifespan."
Kuo and his team first found a positive correlation between triacylglycerol (TAG) content, a form of fat found in all eukaryotes including animals and plants, and lifespan. Although scientists know that TAG gives organisms the ability to store excessive amounts of energy, which can provide insulation to many stressors, the mystery lies in how it is connected to lifespan.
"Our team used genetic approaches to manipulate the cellular capacity of triacylglycerol reproduction and degradation," Kuo said. "Via sophisticated analyses, we demonstrated that it preserves life through a mechanism that is largely independent of other lifespan regulation pathways common in yeast as well as humans."
The team first deleted TAG lipases, which are enzymes that break TAG down into smaller molecules, leading to yeast accumulating fat inside of their cells. Furthermore, Kuo and his team boosted the enzyme responsible for TAG synthesis, effectively increasing production of the lipid.
The results showed that in both cases, blocking TAG breakdown and increasing its production led to fatter yeast cells and a prolonged lifespan, contrary to lean yeast cells which did not have the ability to synthesize TAG and died early. Additionally, forced TAG in a normal strain leads to its breakdown, which also leads to a decreased lifespan.
Another interesting finding of the study is that the yeast cells with increased TAG did not suffer from any noticeable growth defects and showed normal mating and standard resistance to environmental stresses.
Kuo believes that this sort of pro-longevity function is present in humans as well, although its connection to TAG has yet to be proven.
"Our paper likely will stimulate a new wave of research that has broad and deep impacts, including potential advances in human medicine," he said.
The findings were published in the Feb. 23 issue of PLoS Genetics.
