RT Journal Article SR Electronic T1 Feeding intervention potentiates the effect of mechanical loading to induce new bone formation in mice JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.12.27.424485 DO 10.1101/2020.12.27.424485 A1 Hasmik Jasmine Samvelyan A1 John Cummings Mathers A1 Timothy Michael Skerry YR 2021 UL http://biorxiv.org/content/early/2021/01/11/2020.12.27.424485.abstract AB The benefits of increased human lifespan depend upon duration of healthy, independent living; the healthspan. Bone-wasting disorders contribute significantly to loss of independence, frailty and morbidity in older people. Therefore, there is an unmet need globally for lifestyle interventions to reduce the likelihood of bone fractures with age. Although many mechanisms are involved in disorders of bone loss, there is no single regulatory pathway and, therefore, there is no single treatment available to prevent their occurrence. Our aim in these studies was to determine whether fasting/feeding interventions alter the effect of mechanical loading on bone anabolic activities and increase bone mass. In young 17-week-old mice, 16-hour fasting period followed by reintroduction of food for 2 hours increased markedly the potency of mechanical loading, that mimics the effect of exercise, to induce new cortical bone formation. Consistent with this finding, fasting and re-feeding increased the response of bone to a loading stimulus that, alone, does not stimulate new bone formation in ad-lib fed mice. Older mice (20-months) experienced no potentiation of loading-induced bone formation with the same timing of feeding interventions. Interestingly, the pre-, prandial and postprandial endocrine responses in older mice were different from those in young animals. The hormones that change in response to timing of feeding have osteogenic effects that interact with loading-mediated effects. Our findings indicate associations between timing of food ingestion and bone adaptation to loading. If translated to humans, such non-pharmacological lifestyle interventions may benefit skeletal health of humans throughout life-course and in older age.Significance statement Here we report a significant translational finding in ageing research and bone biology. The effect of mechanical loading on bone is increased in mice by altering timing of a fasting/feeding intervention. We show that a fast and reintroduction of food results in a 36% increase in mechanically-induced bone formation. Furthermore, the intervention transforms a mechanical stimulus that is ineffective alone in inducing bone formation into one that does. In humans, a similar potentiation of the effect of exercise following, but not preceding eating has been reported. As it is hard for people to exercise vigorously as they age, there is a need to identify more effective ways to exercise for maximum benefits to the musculoskeletal system.Competing Interest StatementThe authors have declared no competing interest.