The old adage “You are what you eat” may be even more important when it comes to diet and aging. Older people have different nutritional needs from younger ones — and a healthy diet is linked to a lower incidence of cognitive decline. Researchers at the USC Leonard Davis School of Gerontology have been studying the ways that different diets impact health span and the needs that older people have.

For years, scientists have known that restricting calories — in organisms from yeast to mice and other mammals — leads to a longer life when it’s done without creating malnutrition. But researchers are starting to understand why this happens — and how to mimic these results in a way that’s easier to maintain. Other research is focusing on the types of diets that can achieve the healthiest long lives.

Food power

Cary Kreutzer, director of the Master of Science in Nutrition, Healthspan and Longevity Program, works with the Los Angeles Department of Aging, talking with older adults who participate in meal programs through the U.S. Administration on Aging. “Longevity in the aging process, that is an area of great interest on the aging spectrum,” she says.

When she talks with these older adults, she equates understanding food labels with food power — the power to know what they are putting into their bodies. It’s easy for older people to slide toward highly processed foods, as shopping and cooking can become challenging for aging hands. But Kreutzer tries to demystify the process as much as possible in her work.

She has some tips: For one, stay away from ketogenic diets. “Any diet that cuts out bread and fruit will not provide adequate nutrients and is difficult to sustain long-term, because you miss that stuff,” she says. And that boredom means people will drop the diet and gain weight back.

As for the Mediterranean diet? It’s great, Kreutzer says — less red meat, more seafood, beans and olive oil, and fewer processed foods like chips and cookies. But that’s not the whole story. “The Med diet is not just about food; it’s about lifestyle,” she says, including daily physical activity. “I really wish people in the U.S. could embrace the lifestyle of the Mediterranean and not just the diet choices.”

She’s also excited about nutrigenomics, the study of the effects of nutrients on the expression of an individual’s genetic makeup. One example of how this works involves a genetic defect in processing folic acid from a gene called MTHFR. Some women with this genetic single-nucleotide polymorphism (SNP) may need to take a different form of folic acid while they are pregnant to prevent neural tube disorders in their fetuses. Diets based on genetic testing is an emerging science that may help people figure out what nutrients their bodies need.

Kreutzer points out that certain genetic SNPs make people perceive the taste of cilantro as soap or make it difficult to metabolize caffeine. “This field is just in its infancy,” she says, “but the possibilities are great.”

A diet to extend life

Valter Longo, a professor of gerontology and biological sciences, has been working in nutrition and longevity for a long time, and he says he’s seen diets come and go like the fashion of the week. People often look for short-term fixes for their health or weight without looking at the ability of a particular diet to lengthen their lives. In Longo’s view, the body is like a machine, and certain diets can enable that machine to be more efficient in how it uses food.

His lab has developed an intervention, the fasting-mimicking diet, which provides for the benefits of fasting while allowing the consumption of food. In 2018, he wrote a book about the Longevity Diet, an everyday pescatarian diet combined with five-day periods of the fasting-mimicking program implemented four times a year.

Longo says he’s trying to move the idea away from fad diets and into five pillars of science: clinical studies, basic research, epidemiological studies, studies of long-lived people, and complex systems. Eventually, he says, diets will be personalized, but he thinks most people can benefit from the type of eating he describes. A recent meta-analysis looking at China, Europe and the Americas showed that the Longevity Diet could extend life expectancy by up to 13 years if started at age 20.

He says the study of diets — which has long been considered a soft science — needs to become much more rigorous to get to the truth of how food and fasting impact the body. He envisions doctors prescribing a diet along with drugs for cancer treatment or other diseases to improve a person’s outcome.

For example, Longo’s research has shown that cycling a fasting-mimicking diet enables 40% to 70% of diabetes patients to reduce their drug use. “That’s basically saying, if drug use is reduced within six to 12 months, it isn’t unreasonable to think that in a few years, a lot of these patients are going to be essentially cured,” he says. “I think that in some cases, nutrition can also go after cures for specific diseases.”

What happens when you eat after fasting

Sebastian Brandhorst studies dietary-based interventions to improve overall longevity — as well as health span. “Our goal is not to make people live longer just for the sake of making life longer,” he says, “but we want them to live longer and healthier.”

The research assistant professor of gerontology is studying the application of the fasting-mimicking diet to a number of aging-related diseases, including cancer, Alzheimer’s and autoimmune diseases. Some of the results have been translated into clinical trials.

But his focus is now on a particular moment in the fasting period: what happens when people consume food again. Brandhorst says there’s good evidence to show that a turnover and activation of stem cells occurs, which can lead to tissue rejuvenation — the regeneration of tissues following the fast.

To study what happens during the refeeding period, he is testing several dietary approaches, modulating what mice eat — a low-protein or ketogenic diet, or any other dietary intervention — to see what happens in their tissue samples. For example, researchers can look at how brain cells react to different foods after a fast in mice that mimic Alzheimer’s patients. “And can we optimize this regeneration even further by modulating the feeding period?” he says. “That’s where our research is going right now, and it’s what we’re most excited about.”

Brandhorst’s big goal is to improve overall health — and he takes a system approach. “We’re not usually particularly interested in just one specific protein, what happens to that protein over time,” he says. “Instead, we’re always looking at the big picture: Is it feasible? Is it extending lifespan? Can it be translated to humans?”

Brandhorst adds that he sees a big misconception in the need for high protein intake. Studies show that up to age 60 or 65, low animal-based protein consumption is beneficial with regards to health and longevity. After that, there is evidence that higher protein intake is better to maintain lean muscle mass and avoid frailty. When he sees high-protein diets in kids and younger adults, he feels it’s the wrong diet. “I think there’s a big misconception based on gym culture but also marketing,” he says. “There are high-protein drinks for kids, or high-protein pancakes, and they’re not good meals.”

Why we choose the diet we do

Sean Curran, professor and vice dean of the USC Leonard Davis School, says diets should be personalized to the individual — but more research is needed on how an individual’s genetics, environment and socioeconomic status blend with the food they eat. He is also interested in how an individual’s microbiome influences the impact of the food they eat, including nutritional value, satiety and how each person uses or stores the energy they ingest.

Curran’s current research uses a small nematode, C. elegans, to examine how microbes influence the health and longevity of the organism. “We’ve found that diet can compensate for genetic deficiency,” he says. “A mutation in a gene that causes health decline later in life and short lifespan can be masked by simply feeding the animal a different diet.”

His lab has also identified diets that are longevity promoting, but there’s a catch. When given the choice, animals select any other food option available besides the longevity-promoting diet. “This provides a really great model to study how an animal makes decisions about what food to eat,” he says. He’s thinking a lot about what the basis of this choice is: Taste? Smell? Feel? Or something else entirely? “There are lots of exciting new directions.”

What happens in a low-nutrient environment

For years, it’s been documented that restricting calories — without causing malnutrition — is the gold standard to improve health span and extend life. Cristal Hill, assistant professor of gerontology, evaluated anti-aging diets in a recent review article published in the journal Science. She and co-authors focused on the many ways that cells respond to diets that are low calorie or that vary in macronutrients (i.e., carbohydrates, fat and protein) to identify potential targets for pharmaceuticals.

Hill has also been studying the overall health impact of a low-protein diet and why it appears to extend the lifespan. In 2021, she published research showing that a single liver-derived metabolic hormone, known as FGF21, induced by a low-protein diet appears to be responsible for lifespan extension in male mice. She’s now doing more to investigate the pathways that improve the function of adipose tissue, or body fat, to support healthy aging while on a low-protein diet.

Hill says it’s important to think not just about food but also about how to implement nutrient-dense foods into a lifestyle — and eating right for each stage or state of a person’s life. “This understanding of nutrition and healthy aging is moving into precision nutrition or precision medicine,” she says.

Mediterranean diet and maintaining weight

Roberto Vicinanza, instructional associate professor of gerontology at the USC Leonard Davis School and a specialist in geriatric medicine, has studied the Mediterranean diet for years — as well as the impact that diet has on cardiovascular disorders. He says the diet — which stresses fruits and vegetables, cereals, legumes, extra virgin olive oil, nuts and fish — is strongly linked to positive health outcomes.

In one study published in 2018, Vicinanza found that the Mediterranean diet was inversely associated with cardiometabolic disorders and with polypharmacy, suggesting that improved adherence might potentially delay the onset of age-related health deterioration and reduce the need for multiple medications. His research has also found that the diet seems to have a positive impact on mental health, with people who adhere strictly to it being less likely to have depressive symptoms. All of it points to the importance of whole foods and living a balanced lifestyle.

It’s also important to maintain a steady weight to improve lifespan, Vicinanza says. Weight fluctuations in older adults are associated with an increased risk of chronic diseases. “Not only may being underweight after age 65 compromise health status and increase the risk of malnutrition, but weight fluctuations may also have negative effects,” Vicinanza says. “It’s good to have a stable weight and preserve muscle mass. This is the reason why we shouldn’t rely only on the weight you see on the scale but also consider a comprehensive evaluation of body composition.”