Caloric restriction and body weight independently affect longevity in Wistar rats

Area of Science:

• Longevity research
• Metabolic studies
• Animal models in aging

Background:

• Caloric restriction (CR) is known to extend lifespan in various organisms.
• The interplay between CR, body weight (BW), and mortality rate (MR) requires further elucidation.
• Understanding these relationships is crucial for developing interventions to promote healthy aging.

Purpose of the Study:

• To independently assess the effects of CR and BW on MR in Wistar rats.
• To determine the extent to which BW mediates the impact of CR on MR.
• To provide insights into the mechanisms underlying CR-induced longevity.

Main Methods:

• Utilized data from the Biosure Study, a prospective, randomized controlled trial involving 1200 Wistar rats.
• Employed Cox regression analysis to evaluate the independent and combined effects of CR and BW on MR.
• Applied bootstrap procedures and mediation analysis to quantify the role of BW in mediating CR's effects on MR.

Main Results:

• CR initiated after 13 weeks of age significantly decreased subsequent MR.
• Higher BW in early adulthood was associated with increased MR, an effect independent of CR.
• Mediation analysis revealed that low BW associated with CR accounted for approximately 11% of CR's mortality-reducing effects, indicating CR also has independent benefits.

Conclusions:

• Both CR and BW exert independent influences on MR in Wistar rats.
• BW acts as a partial mediator, explaining a small fraction of the mortality benefits of CR.
• CR demonstrates significant mortality-reducing effects beyond its impact on body weight.