Skeletal effects of long-term caloric restriction in rhesus monkeys

Abstract

Age-related bone loss is well established in humans and is known to occur in nonhuman primates. There is little information, however, on the effect of dietary interventions, such as caloric restriction (CR), on age-related bone loss. This study examined the effects of long-term, moderate CR on skeletal parameters in rhesus monkeys. Thirty adult male rhesus monkeys were subjected to either a restricted (R, n0 15) or control (C, n015) diet for 20 years and examined throughout for body composition and biochemical markers of bone turnover. Total body, spine, and radius bone mass and density were assessed by dualenergy X-ray absorptiometry. Assessment of biochemical markers of bone turnover included circulating serum levels of osteocalcin, carboxyterminal telopeptide of type I collagen, cross-linked aminoterminal telopeptide of type I collagen, parathyroid hormone, and 25(OH)vitamin D. Overall, we found that bone mass and density declined over time with generally higher levels in C compared to R animals. Circulating serum markers of bone turnover were not different between C and R with nonsignficant diet-by-time interactions. We believe the lower bone mass in R animals reflects the smaller body size and not pathological osteopenia.

Biology of Human Aging and Recent Nutrition Therapy

“…Furthermore, the negative effect on musculoskeletal system [20] suggested in rhesus monkeys has also been confirmed in humans [21]. From the above, it is time to need a scientific re-evaluation on the effectiveness and safety of CR.…”

Dietary restrictions, bone density, and bone quality

“…In a human study, middle‐aged lean individuals with long‐term (>6 years on average) restricted daily caloric consumption (∼35% less than the control group) showed significantly lower levels of serum C‐reactive protein without showing a difference in cancellous bone architecture parameters or bone turnover markers compared to a sedentary control group . Similarly, in animal studies, rhesus monkeys that had a lifelong CR diet also showed decreased oxidative stress, whereas they displayed no differences in bone metabolism or bone mineral mass compared to a control group fed ad libitum . In rodents, CR caused a reduction in serum TNF‐α and IL‐1 of type 2 diabetic Otsuka Long‐Evans Tokushima fatty rats without affecting the serum bone markers or densitometric indices .…”

“…Most importantly, dietary restriction–related comprehensive efficacies in the downregulated inflammatory responses and oxidative stresses are distinct from the high inflammatory/ROS levels that are a result of pathologically related type 2 diabetes, estrogen deficiency, and anorexia nervosa . This suggests that the lower bone mass caused by dietary restriction is mechanistically different from pathogenesis‐related osteoporosis or osteopenia …”

Nutrition, metabolism, and targeting aging in nonhuman primates

“…CR has long been associated with lower bone mass and lower bone mineral density that, until quite recently, was viewed as a potentially negative outcome 42 . It has become clear that bone density is markedly influenced by body weight and in this light the lower bone density measured in CR animals could be viewed as an adaptive rather than a pathological outcome of the diet 43,44 . Although the starting point is different for control and CR monkeys, the rate of decline in bone mass and bone density is greater in the controls suggesting a protective effect of CR.…”