As research on extending lifespan and healthspan has progressed over the last two decades, an adage of “eat less, live longer,” has emerged as many different researchers, institutes, papers, and analyses seemed to indicate that a reduction in calories leads to an increase in lifespan and healthspan.

World at Large has reported on such science in several instances, but a new paper from the Buck Institute for Research on Aging has, in an act true to the essence of science, complicated the body of work they have been hugely responsible for advancing.

In it genetic markers for healthspan didn’t always correlate positively for lifespan under conditions of calorie-restriction or fasting, and vice-versa was also found.

While eating a Spartan diet has been shown to robustly extend lifespan and delay age-related diseases in many species, including humans, a genome-wide analysis of 160 genetically distinct strains of the fruit fly D. melanogaster shows that lifespan and healthspan are not linked under dietary restriction.

The fruit fly study

In the gene-wide associated study (GWA) of fruit flies, changes in lifespan that were observed as dependent on nutrients were tracked along with age-related changes in physical activity as a marker of healthspan. Only 50% of the fruit fly strains showed significant positive responses to these markers during caloric restriction for either lifespan or healthspan or both.

13% percent of the fruit fly strains were more physically vigorous yet died sooner with dietary restriction while 5% percent lived longer but spent more time in poor health. The remaining 32% of the strains showed no benefits or detriments to lifespan or healthspan, or negative responses to both.

“Dietary restriction works, but may not be the panacea for those wanting to extend healthspan, delay age-related diseases, and extend lifespan,” said Pankaj Kapahi, PhD, Buck professor and senior author on the paper.

“Our study is surprising and gives a glimpse into what’s likely going to happen in humans, because we’re all different and will likely respond differently to the effects of dietary restriction. Furthermore, our results question the idea that lifespan extension will always be accompanied by improvement of healthspan”.

Genes matter

The Buck Institute GWA studies identified and named a fruit fly gene that regulates lifespan, which they called decima, after the Roman god of fate. Inhibiting this gene extended lifespan by reducing the production of insulin-like peptides, but did not improve age-related decline in climbing activity, which was used to track physical ability in the flies.

They also named another gene daedalus, after the Greek mythological character of the same name who escaped prison with his son Icarus by crafting artificial wings. Inhibiting daedulus delayed the age-related decline in physical activity upon dietary restriction, but only minimally influenced lifespan.

Dr. Kapahi also noted that climbing ability, used to track physical ability in the flies, is just one measure of healthspan.

“Other traits associated with healthspan are also important to measure. We need to understand the genetics of age-related decline in other functions, such as vision and cognition. Working in simple animals, like the fruit fly is a great place to do this efficiently”.

“One lesson we have learned is that lifespan extension should not be the gold standard for determining the best means of dealing with age-associated maladies,” he said.

The GWA studies examined 50,000 individual fruit flies over the course of the study, which Kenneth Wilson Ph.D. and Buck Institute member said circumnavigated a lot of problems in dealing with genes at the level of the individual animal.

“With this method, we can ask questions in a much more robust manner and get answers at the population level,” said Wilson.

Often in the history of science, a body of work presumed as fact is challenged by new evidence. For neutrals, it’s both a good sign that a study like this which challenges the narrative was published both early in the scope of the longevity research, and also by scientists who stand to lose the most from its publishing.

“People need to be aware that their genetic background will likely have a major impact on how they will respond to an intervention. There is a need to develop markers in the field so we can predict how an individual will react to any particular intervention in terms of improving health and lifespan,” said Dr. Kapahi.

Continue exploring this topic — What if There Were a Drug that Tricked Your Body into Thinking it was Fasting?