Researchers have discovered a specific genetic mutation responsible for a mitochondrial disease observed in mice that quickly ages nine month-old specimens that present with osteoporosis, thinning grey hair, infertility, poor hearing, heart problems and lost weight. The mice carry this disease from birth, but researchers have also found that some harness a “secret weapon” that temporarily staves off the aging process — a development that could have implications for treating mitochondrial disease in humans.
A recent research project from the Salk Institute shows how a longevity hormone can assist these mice that carry thousands of mutations in their mitochondria, the energy-generating organelle, in order for them to maintain metabolic homeostasis at a younger age. This hormone could lead to the development of new therapies with the potential to address mitochondrial and metabolic diseases.
“These findings help us understand the link between diet, health and aging, and they give us the potential to dissect these connections in a molecular way that could lead to therapeutics,” said Ronald Evans, who is the director of Salk’s Gene Expression Laboratory and senior author of the article published in June 29, 2015 in Proceedings of the National Academy of Sciences.
Researchers found that the longevity-promoting endocrine hormone FGF21 was very active, even the animals showing accelerated aging.
“FGF21 is classically thought of as an anti-aging gene, turned on by exercise or fasting and suspected to extend lifespan. Yet these mice ultimately age prematurely, despite having high levels of this hormone,” noted Christopher Wall, first author of the study.
FGF21 assists stressed mitochondria and plays the role of reprogramming their metabolic state. Evans and the rest of the team described how FGF21 switches tissues from burning sugar to burning fat, the easiest fuel for dysfunctional mitochondria.
Michael Downes, a researcher involved in the study, added: “This works for a while in these mice, but eventually their bodies run out of fat to burn. FGF21 needs some additional fat from the diet to keep working.”
Evans noted: “What we believe now is that turning on FGF21 is an adaptation to help this animal maintain its metabolic health. If the mice didn’t have this hormonal ‘fountain of youth,’ they might age even more quickly than they already do.”
This study has the potential to affect human health in several ways. High levels of FGF21 were also observed in individuals with mitochondrial diseases and consuming more fat in diets could ease their symptoms; also, utilizing drugs to mildly stress mitochondria could lead to a beneficial FGF21-dependent metabolic shift in patients with obesity and other metabolic issues.
“We want to look at the interaction between FGF21 and dietary fat in human patients with mitochondrial disease now and start to see how we can manipulate this dynamic in different ways,” said Downes.