Caloric restriction

Trial registry update: COMPLETED. No results reported in the supplied registry record.

Trial registry update: UNKNOWN. No results reported in the supplied registry record.

This systematic review examined mTOR signaling as a hub coordinating aging processes across genetic, experimental, and translational studies. In model organisms, mTOR pathway inhibition shows causal effects on lifespan regulation, whereas human data remain predominantly observational and associative. The review identifies mTOR as an integrative node linking multiple aging hallmarks and notes that major geroprotective interventions—including autophagy activation, dietary changes, physical activity, and senotherapeutics—partly converge on but also diverge from mTOR pathway modulation.

Researchers compared liver oxylipin (lipid mediator) profiles between ad libitum-fed and calorie-restricted mice across adulthood and aging. Ad libitum-fed mice showed a shift toward pro-inflammatory oxylipins around 9 months, followed by depletion of cytoprotective epoxides and accumulation of diols in later life. Caloric restriction blunted these inflammatory shifts, preserved epoxy-fatty acids, and induced CYB5R3, an enzyme that may sustain epoxide production despite reduced overall enzyme levels.

This randomized controlled trial evaluated the safety, feasibility, and preliminary efficacy of low-dose daily rapamycin (1 mg) or fasting-mimicking diet (FMD) compared to placebo over 8 weeks in middle-aged adults carrying the APOE ε4 allele, a genetic risk factor for Alzheimer's disease. The study aimed to assess outcomes related to body, brain, and longevity in this at-risk population. No results of the intervention were reported in the abstract provided.

DiAL Health is a 24-week randomized controlled pilot trial enrolling 90 healthy adults aged 22–45 into five groups: nonintervention control, traditional or adaptive time-restricted eating (8-hour window), and traditional or adaptive caloric restriction (25% energy reduction). Adaptive interventions used mobile health technology with real-time monitoring and personalized feedback; traditional interventions used in-person counseling. Primary outcomes were feasibility measures (adherence, retention, satisfaction); secondary outcomes included biological age (Klemera-Doubal) and metabolic syndrome score. No efficacy results have been reported yet.

This was a Phase III randomized controlled trial in people with metabolic syndrome designed to test whether metformin and comprehensive lifestyle changes (moderate physical activity, Mediterranean/macrobiotic diet with calorie and protein restriction) prevent age-related chronic diseases. The abstract describes only the study design and aims; no results or outcomes are reported.

This RCT tested whether a combination of lifestyle intervention (weight loss and exercise) plus metformin was effective for reversing sarcopenic obesity and frailty in older obese Veterans. The abstract describes the study hypothesis and population but does not report results, sample sizes, or effect sizes.