Caloric restriction is well researched as an anti-aging strategy with its clinical development widely established. The 2-year clinical trial NCT00427193 by Duke University enrolled over 200 people to research the effect of a 25% calorie restricted diet on aging and age-related disease processes. Outcome measures included change in core body temperature, resting metabolic rate, inflammatory marker TNFα, along with fat mass. The effect of calorie restriction included significant decreases in both inflammatory markers and cardiometabolic risk factors which suggests potential benefits for aging and age-related disease processes. The University of Alabama also researched the use of caloric restriction along with exercise for the reduction of cardiometabolic risk. Phase III clinical trial NCT00955903 enrolled 167 participants with outcome measurements of change in abdominal fat mass, cardiometabolic risk factors, and weight change. Study results show significant improvement to relative fat mass, biomarker adiponectin and leptin, and cardiometabolic risk measurements for the intervention arm. Researchers are also currently investigating how caloric restriction can affect biological aging and neurodegenerative diseases such as cognitive impairment and Alzheimer's disease. TruDiagnositic is conducting an active phase II trial with 50 subjects enrolled to investigate the use of Peak Human Labs calorie mimetic supplement along with a fasting mimicking diet to see their effect on biological aging. The intervention group will take the supplement for 90 days mixing in a 5-day fasting diet three times. Outcome measurements include the epigenetic age biomarkers which will test methylation at 850,000 locations on the DNA and body max index. Another active study performed by the University of Kansas hopes to learn how the Mediterranean diet compared to a low-fat diet for 12 months affects cardiometabolic biomarkers, brain antioxidant status, brain volume, and memory in cognitive normal adults aged 65 or greater. Researchers plan to examine brain processes to understand health and how the Mediterranean diet may help treat Alzheimer's disease in the future. The University of Genova is also currently recruiting for its phase I/II study which will investigate the use of a specific 5-day low protein fasting diet called Prolon ADTM. 40 participants will be enrolled, and the treatment group will consume the diet once a month for a 12 months. Metabolic, inflammatory, and regenerative pathways will be monitored to see the diet's effect on mild cognitive impairment and early Alzheimer's disease. 687