Precision nutrigeroscience: No “one size fits all” approach to anti-aging, spotlights new framework

23 Sep 2021 --- The health and longevity benefits from dietary restriction vary, spurring researchers to create a new framework to study precision nutrigeroscience. This takes into account biomarkers affected by genetics, gender, tissue and age.

“Everyone is hoping for a ‘one size fits all’ intervention when it comes to diet. Work in our lab and several others shows that this is simply not going to be the case,” says Pankaj Kapahi, a professor at the Buck Institute for Research on Aging.

Kapahi’s team aims to understand the mechanisms by which nutrient signaling and metabolism influence aging and age-related diseases. They have now published a review in Cell Metabolism that challenges the nutrition field to change its approach to dietary restriction while aiming for precise, individualized interventions. 

A mixed picture
Types of dietary restriction range from caloric restriction to various forms of intermittent fasting as well as diets that restrict proteins, carbohydrates, specific amino acids, micronutrients and metabolites.

Current data from humans shows dietary restriction has positive effects on neurodegeneration, diabetes, cardiovascular disease and kidney disease.

However, the authors report that there are indications that restricting the food we eat could lower bone mineral density, leading to osteoporosis.

The picture continues to be blurry when examining other areas of health. For example, while muscle preservation is upregulated with dietary restriction, data also shows that muscle growth is inhibited. The authors say exercise could ameliorate those deficits, adding another factor that needs to be considered when studying the effects of dietary restriction.

Furthermore, while data shows that respiratory function is improved with dietary restriction, it also reveals that exercise capacity could go down at the same time.The framework is based on optimizing diet-based interventions to optimize health and longevity to accommodate factors that lead to individual variation.

Changing attitudes toward aging
Kapahi has changed the way he looks at aging. “A lot of us get very deep into the minutia of understanding what I call two-dimensional biological pathways.”

“We are forgetting a whole other dimension which is that these pathways are different in each individual and within tissues in individual bodies. Context matters, and we can’t make real progress in this field without including that.”

He argues that the field could end up being damaged because eventually interventions will not  work and then people will get disappointed.

Genetic factors
Buck postdoc Kenneth Wilson is the first author of the review. He previously carried out a genome-wide analysis of 160 genetically distinct strains of fruit flies that ate the same Spartan diet. The team showed that lifespan and healthspan were not linked under dietary restriction.

While 97% of strains showed some lifespan or healthspan extension on the limited diet, only 50% showed a significantly positive response to dietary restriction for both.

“It’s important for everyone in the field to understand and appreciate that there are a lot of different ways to look at what an intervention might be doing. You might see a response in one case, but that response might not work in another strain of the same species.” 

“Conversely, if you’re not seeing something, that doesn’t mean that the intervention you’re testing doesn’t work, it just means you’re not using the right model for that intervention.”

He continues that it is also crucial that researchers be aware of the possible disconnect between extending lifespan and healthspan when it comes to diet. “The last thing any of us want to do is give people more years of ill health.”Effective therapeutics may have been discounted because they haven’t tested well in a particular strain or species of a model organism.

Taking age and gender into account
Measuring aging in response to dietary restrictions can be complex. However, lifespan analysis is used to decipher the mechanisms of dietary restriction, possible gene-specific lifespan responses to dietary interventions, and the role of gender in species that have males and females.

“When it comes to DNA, human males have more in common with the male chimpanzee than with human females,” points out Kapahi.

In flies and mice, females are much more responsive to dietary changes than their male counterparts, likely based on the physiological effects on the female reproductive system and its interplay with other systems. Until recently, most studies in mice and humans disproportionately involved males.

“The age of the person utilizing dietary restriction is also a factor that needs to be studied and considered,” says Wilson. 

“It’s been shown that people who are older may not want to limit their dietary intake, especially when it comes to protein which helps preserve muscle mass.”

The bottom line
Kapahi emphasizes that if scientists can frame dietary restriction within the context of precision medicine, everything that people are learning in the field will apply to the larger effort, which is all about improving and extending human health.

“The bottom line is there is no ‘negative’ or ‘positive’ data – we can glean insights from all of it, and it will take a large team effort to fully develop precision nutrigeroscience.”

He argues that there are likely effective therapeutics that already exist that have been discounted because they haven’t tested well in a particular strain or species of a model organism. “There is a real benefit in giving up the search for a ‘one-size-fits-all’/’magic pill’ solution to the physical problems of aging.”

Consumer interest in personalized nutrition is picking up pace, with Innova Market Insights reporting that 64% of global consumers have found more ways to tailor their life and the products they buy to their individual style, beliefs and needs. 

In June, a report from the UK House of Commons Science and Technology Committee called for tighter restrictions around direct-to-consumer genomic tests. 

Edited by Katherine Durrell