Bone Abstracts

Loss of genomic maintenance contributes to aging, as exemplified by mutations in Ercc DNA repair proteins that lead to a plethora of progeroid syndromes of which some display accelerated bone loss. It is generally accepted that dietary restriction (DR) increases life span and improves organ function. We therefore assessed the impact of DR on life span and bone mass in WT and bona fide prematurely aging hypomorphic Ercc-deficient mice (Ercc1^−/Δ).

Female and male WT and Ercc1^−/Δ mice were fed ad libitum (AL) until 7 weeks of age after which they were split up in 30% DR (initiated with 10% per week increments) and AL groups. Femurs were collected at several ages and micro-computed tomography was performed.

DR-fed Ercc1^−/Δ mice increased their life span to over 30 weeks compared to 20 weeks for AL-fed mice. At 11 weeks of age, femur length was significantly reduced in female (13.4±0.4 vs 15.5±0.5 mm; P<0.001) and male (13.5±0.5 vs 15.9±0.4 mm; P<0.001) Ercc1^−/Δ vs WT mice, consistent with reduced growth. DR did not alter femur length in these groups. AL-fed Ercc1^−/Δ mice had a significantly lower trabecular bone volume fraction (BV/TV) vs WT mice (females: 5.8±1.8 vs 10.7±3.2%; P<0.001, males: 7.4±1.5 vs 13.2±2.0%; P<0.001). In male WT mice (non-significant in females), DR reduced BV/TV (34.8%, P=0.002) but in Ercc1^−/Δ mice this was elevated (38.2%, P=0.002). The initial bone mass was increased in the DR-fed Ercc1^−/Δ, but thereafter bone loss rate was similar between diets. Effects on trabecular thickness showed similar non-significant trends.

Conclusion: DR reduces bone mass in WT mice but it prolongs life span and delays bone loss in Ercc1^−/Δ mice. The differential response to DR in WT vs Ercc1^−/Δ mice and the DR-triggered temporal increase in bone mass in Ercc1^−/Δ mice deserve further mechanistic scrutiny but may be related to genotype-driven effects on bone at young age.