Scientists at the Buck Institute for Research on Aging report that a protein involved in nutrient sensing and metabolism does not work properly in male mice fed a high-fat diet. However, female mice are not affected.
When the researchers boosted this protein, it protected male mice from age-induced obesity and metabolic problems.
Senior author Brian Kennedy, Ph.D, explained that differences in aging between men and women have been known for some time, but previous studies investigating aging in mice have led to interventions working better in males or females.
But Kennedy believes his team’s new findings could identify a potential mechanism that explains the differences between males and females.
Originally, they were investigating the TOR (target of rapamycin) pathway, which is linked to aging. Previous studies have shown that reducing TOR signalling can extend the lifespan of mice.
They discovered that a protein component of the TOR pathway, called 4E-BP1, is regulated differently in male and female mice.
The 4E-BP1 component is believed to play a protective role in insulin sensitivity and the maintenance of fat cells, and male mice with restored 4E-BP1 became much more like female mice.
“They still got obese when they ate a high-fat diet, they just didn’t develop as much diabetes,” said lead scientist Shi-Yin Tsai, Ph.D. “They also accumulated less of the white ‘belly fat’ associated with diabetes and had lower levels of circulating lipids and triglycerides.”
Kennedy added: “We found this phenomena with 4E-BP1 because we were doing the experiments in both male and female mice and we saw the difference. Gender is an essential part of the equation.
“Most preclinical work in diabetes is done in male mice because they get the disease quicker which makes the experiments cheaper and faster to do. I understand that reasoning, but we are likely missing crucial information in the process.”
Kennedy’s team are hoping their findings can be used to eventually develop therapeutics that treat type 2 diabetes and other age-related conditions.
The study was published online in Cell Reports.