Examining a range of research from studies in laboratory animals to epidemiological research in human populations gives scientists a clearer picture of what kind of nutrition can offer the best chance for a longer, healthier life, said USC Leonard Davis School of Gerontology Professor Valter Longo.
In an article that includes a literature review published April 28 in Cell, Longo and coauthor Rozalyn Anderson of the University of Wisconsin describe the “longevity diet,” a multi-pillar approach based on studies of various aspects of diet, from food composition and calorie intake to the length and frequency of fasting periods.
“We explored the link between nutrients, fasting, genes, and longevity in short-lived species, and connected these links to clinical and epidemiological studies in primates and humans, including centenarians,” Longo said.
“By adopting a multi-system and multi-pillar approach based on over a century of research, we can begin to define a longevity diet that represents a solid foundation for nutritional recommendation and for future research.”
What – and when – to eat for longevity
Longo and Anderson reviewed hundreds of studies on nutrition, diseases and longevity in laboratory animals and humans and combined them with their own studies on nutrients and aging. The analysis included popular diets such as the restriction of total calories, the high-fat and low-carbohydrate ketogenic diet, vegetarian and vegan diets, and the Mediterranean diet.
The article also included a review of different forms of fasting, including a short-term diet that mimics the body’s fasting response, intermittent fasting (frequent and short-term) and periodic fasting (two or more days of fasting or fasting-mimicking diets more than twice a month).
In addition to examining lifespan data from epidemiological studies, the team linked these studies to specific dietary factors affecting several longevity-regulating genetic pathways shared by animals and humans that also affect markers for disease risk, including levels of insulin, C-reactive protein, insulin-like growth factor 1, and cholesterol.
The authors report that the key characteristics of the optimal diet appear to be moderate to high carbohydrate intake from non-refined sources, low but sufficient protein from largely plant-based sources, and enough plant-based fats to provide about 30 percent of energy needs.
Ideally, the day’s meals would all occur within a window of 11-12 hours, allowing for a daily period of fasting, and a 5-day cycle of a fasting or fasting-mimicking diet every 3-4 months may also help reduce insulin resistance, blood pressure and other risk factors for individuals with increased disease risks, Longo added.
He described what eating for longevity could look like in real life: “Lots of legumes, whole grains, and vegetables; some fish; no red meat or processed meat and very low white meat; low sugar and refined grains; good levels of nuts and olive oil, and some dark chocolate.”
What’s next for the longevity diet
The next step in researching the longevity diet will be a 500-person study taking place in southern Italy, Longo said. The longevity diet bears both similarities and differences to the Mediterranean-style diets often seen in super-aging “Blue Zones,” including Sardinia, Italy; Okinawa, Japan; and Loma Linda, California.
Common diets in these communities known for a high number of people age 100 or older are often largely plant-based or pescatarian and are relatively low in protein. But the longevity diet represents an evolution of these “centenarian diets,” Longo explained, citing the recommendation for limiting food consumption to 12 hours per day and having several short fasting periods every year.
In addition to the general characteristics, the longevity diet should be adapted to individuals based on sex, age, health status, and genetics, Longo noted. For instance, people over age 65 may need to increase protein in order to counter frailty and loss of lean body mass, as Longo’s own studies illustrated that higher protein amounts were better for people over 65 but not optimal for those under 65, he said.
For people who are looking to optimize their diet for longevity, he said it’s important to work with healthcare provider specialized in nutrition on personalizing a plan focusing on smaller changes that can be adopted for life, rather than big changes that will cause an harmful major loss of body fat and lean mass, followed by a regain of the fat lost, once the person abandons the very restrictive diet.
“The longevity diet is not a dietary restriction intended to only cause weight loss but a lifestyle focused on slowing aging, which can complement standard healthcare and, taken as a preventative measure, will aid in avoiding morbidity and sustaining health into advanced age,” he said.
Citrate is a pivotal substrate that mediates cellular energy metabolism. In mitochondria, citrate is produced via condensation of acetyl‐CoA and oxaloacetate by citrate synthase. It then becomes a substrate in the tricarboxylic acid (TCA) cycle and provides the major cellular ATP source.
Cytosolic citrate is required for de novo fatty acid synthesis and derives from either mitochondrial release through a specific citrate carrier or extracellular import by citrate transporters across the plasma membrane. Previous studies have shown that mutations in the gene encoding the D. melanogaster and C. elegans plasma membrane citrate transporter, I‘m Not Dead Yet (Indy), result in improved metabolic fitness and lifespan extension (Rogina et al., 2000; Schwarz et al., 2015; Wang et al., 2009).
A mammalian Indy (mIndy, also called SLC13A5) null mutation in mice also conferred superior metabolic health under high‐fat diet conditions, giving further support to the importance of citrate in metabolic regulation associated with aging (Birkenfeld et al., 2011).
Intracellular citrate can also function as a sensor for regulating energy production, since it inhibits and activates several strategic enzymes involved in glycolysis, the TCA cycle, gluconeogenesis, and fatty acid synthesis (Iacobazzi & Infantino, 2014). Because of its inhibition of glycolysis and the TCA cycle, high‐level citrate supplementation has been proposed as an anti‐cancer intervention, acting through ATP depletion to lead to arrest of cell growth and ultimately, to cell death (Lu et al., 2011; Zhang et al., 2009).
A similar approach to limiting cellular energy is achieved through dietary restriction (DR, 20%–40% reduction in food intake), a well‐documented regimen that has been established as the most effective intervention for prolonging healthy lifespan across multiple species (Lin et al., 2000; Mattison et al., 2017; Tatar et al., 2014; Weindruch et al., 1986).
Studies investigating the underlying mechanism of DR have identified signaling pathways involving nutrient‐sensing and metabolism, such as sirtuins (Sir), AMP‐activated protein kinase (AMPK), target of rapamycin (TOR), and downstream ketogenesis pathways (Kaeberlein et al., 2005; Lin et al., 2000; Newman et al., 2017; Roberts et al., 2017; Stenesen et al., 2013; Teng et al., 2019). Interventions acting on these targets often result in improved metabolic health and lifespan extension (Madeo et al., 2019).
The influence of chronic citrate treatment on metabolism, cognition, and aging at the organismal level remains unknown. Using fruit flies and mice as model organisms, we show that dietary citrate supplementation can promote longevity, improve metabolic health, and enhance memory performance, through a mechanism associated with the AMPK, TOR, and ketogenic pathways.
Our findings thus have critical implications for use of citrate in the treatment of diseases associated with aging.
reference link :https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8672782/
More information: Nutrition, longevity and disease: from molecular mechanisms to interventions, Cell (2022). DOI: 10.1016/j.cell.2022.04.002