Researchers are exploring whether certain food compounds can mimic the effects of calorie restriction, a strategy that has been shown to extend lifespan in various organisms. Calorie restriction involves reducing energy intake by about 20–40% while still meeting essential nutrient needs. While it has been linked to longer life in yeast, rodents, and other animals, evidence in humans remains limited. The World Health Organization (WHO) reports that in 2021, the global life expectancy was 71.4 years, but the number of years people live in good health was 61.9, creating a gap of nearly 10 years. This gap has widened in most countries over the past few decades, highlighting the importance of understanding how to age more healthily. As people grow older, they often experience a decline in muscle strength and mass, reduced aerobic capacity, and a rise in low-grade inflammation, known as "inflammaging." These changes vary among individuals and are influenced by factors such as diet, physical activity, and sleep, as well as socioeconomic conditions and access to healthcare. The largest human trial on calorie restriction, called CALERIE, followed 218 healthy adults for two years. Participants reduced their calorie intake by 12% on average and showed improvements in cardiovascular and metabolic health markers, such as blood pressure and inflammation levels. However, the study did not confirm whether calorie restriction improves functional health or extends life, and maintaining such a diet can be challenging for many. Scientists are now looking into compounds that may offer similar benefits to calorie restriction without requiring significant dietary changes. These compounds, called calorie-restriction mimetics (CRMs), are found in various foods and may influence cellular processes such as autophagy—where cells remove damaged components—or how cells sense energy. One such compound is spermidine, found in foods like wheat germ and mushrooms. Observational studies suggest that higher intake of spermidine may be linked to a lower risk of death, but more research is needed to determine if this is a direct effect or due to other factors. Similarly, compounds like resveratrol, found in grapes, and quercetin, found in onions and apples, have shown some potential in improving muscle function and endurance, but results in human trials have been mixed. While research into these compounds is ongoing, current evidence suggests that overall dietary patterns and physical activity remain the most effective ways to support healthy aging. A large study following over 105,000 adults found that diets rich in fruits, vegetables, whole grains, nuts, and healthy fats were associated with longer, healthier lives. Physical activity is also crucial, with guidance recommending that older adults engage in strength, balance, and flexibility exercises at least twice a week. Diets like the Mediterranean and traditional Okinawan diets, which emphasize plant-based foods and limited processed ingredients, have also been linked to better aging outcomes. While the role of individual CRM compounds in these benefits is still unclear, a balanced, nutritious diet and regular physical activity continue to be the strongest supports for healthy aging.