A planning project to pilot test and optimize dietary approaches to slow aging and design a long-term trial - PROJECT SUMMARY
The world's population is aging in an obesogenic environment characterized by increased availability of high
caloric, non-nutritious foods and reduced needs for physical activity. As a result, more people than ever are
affected by chronic age-associated diseases, such as obesity, heart disease and diabetes. Thus, people are
living longer but with shorter healthspans, or fewer years that are unaffected by disease. This imposes
significant health and economic burdens on people, societies and nations. There is a critical need to develop
and test sustainable lifestyle interventions to slow the rate of biological aging, extend healthspan and enhance
quality of life as people age. One such intervention is calorie restriction (CR), which is defined as eating a
nutritionally adequate diet that is below energy requirements. CR has been studied for almost 100 years and
has been found to extend the lifespan and healthspan of numerous species. When tested in young and middle-
aged humans, modest CR improves healthspan and slows biological aging. Nonetheless, adherence to CR
has been found to decrease over time, calling into question the long-term viability of this approach, though
earlier CR interventions did not benefit from a more advanced intervention approach, namely, a Just-in-Time
Adaptive Intervention (JITAI). JITAIs strive to provide individuals with the right type and amount of personalized
support when needed by adapting intervention delivery to the present needs and environment of the subject. A
possible alternative to CR that may have better adherence and acceptability is time-restricted eating (TRE),
which involves eating one's food in an 8 to 10-hour period of the day. TRE extends the lifespan of rodents,
and, based on recent human trials, TRE improved disease risk factors and biomarkers of aging. Further, many
benefits of TRE were achieved even when weight loss did not occur. In response to RFA-AG-21-016, we
propose a novel planning project to determine the feasibility and preliminary efficacy of CR and TRE, which will
be delivered in traditional intervention formats and as JITAIs. Data from the planning project will be used to
select the CR intervention and identify if and what type of TRE intervention will be tested in a future 5-year trial.
Further, evaluation of CR and TRE JITAIs, in comparison to more traditional approaches, is critical to allow us
to weigh efficacy in relation to the burden of, and satisfaction with, these very different intervention
approaches. Our project will also provide effect size estimates for a suite of primary and secondary aging
outcomes to adequately power a 5-year trial, and it will provide important preliminary data on adherence and
subject satisfaction and safety. Finally, the planning project will bring together a multidisciplinary team of
scientists from across the US and allow the two study sites to establish a common protocol and standardize
procedures necessary to execute a 5-year trial.
