Growth rates were lower in diet-restricted animals than in controls (Ingram et al., 1990; Lane et al., 1992), and diet restriction delayed maturational changes in circulating testosterone levels; food restriction apparently retarded sexual maturation in prepubertal rhesus monkeys by at least 1 year (Roth et al., 1993). Postmaturation serum concentrations of the adrenal androgen dehydroepiandrosterone sulfate decreased in ad libitum-fed young adult male rhesus monkeys at a rate twice that seen in humans (Lane et al., 1997), but diet restriction slowed the postmaturation decline, and this suggests that aging rate, as indexed by adrenal steroid production, can be retarded by nutritional intervention.

Bone

Some age-related changes in the skeleton are common to humans and rhesus macaques (M. mulatta) that are more than 6 years old and are significantly related to BW in both sexes (DeRousseau, 1985a). Although absolute degenerative joint disease in rhesus can differ between populations, rates of age-related decline in skeletal integrity tend to be similar in all age groups examined (DeRousseau, 1985b).

The effect of maturation and subsequent aging on bone mineral content and two dimensional bone area was examined in female rhesus macaques aged 2.8-34.6 years (Champ et al., 1996). Total body, lumbar spine, and distal radial DEXA scans were performed. At all sites bone mineral content was correlated with bone area, which was positively correlated with BW and age. Total body and lumbar spine bone mineral concentration and bone area increased with maturation until age 11 and then stabilized. Significant bone loss at older ages was observed only at radial sites. The skeletal effects of aging and menopausal status were studied in female rhesus macaques ranging in age from 4-30 years (Colman et al., 1999a). Total body and posterior-anterior spinal bone masses were lower in growing than in adult premenopausal females. Postmeno-pausal females had lower total body, distal radius, and spinal bone masses than premenopausal females. Serum osteocalcin concentrations (marker of bone turnover) were higher in post- than in premenopausal females. Spinal osteoarthritis became common in older females, causing an increase in DEXA-measured bone mass in lumbar spinal posterior-anterior projections. The skeletal effects of aging in male rhesus macaques include reaching peak bone mass at about 10 years of age, after which bone mass is lower at the lateral spine and distal radius (Colman et al., 1999b). Markers of bone turnover, such as serum concentrations of osteocalcin and carboxyterminal telopeptide of type I collagen, decline with age. With advancing age, the prevalence of lumbar spine osteoarthritis increases dramatically, as in females, and may mask decreases in posterior-anterior spinal bone mass. Diet restriction to 30% below ad libitum-fed controls for more than 6 years affects bone growth and skeletal aging in male rhesus monkeys even if daily mineral and vitamin intakes exceed recommended intakes by 40% (Lane et al., 1995c).

Long-term food restriction of younger monkeys resulted in a significant delay in the developmental decline (to adult concentrations) in serum alkaline phosphatase concentrations, slowed skeletal growth (as reflected by shorter crown-rump length), and significantly reduced total body bone-mineral content but not bone-mineral density (as measured by DEXA absorptiometry). Serum calcium and phosphorus concentrations declined significantly with age (P < 0.005) but were not significantly altered by diet restriction. Those findings suggest that long-term diet restriction delays skeletal development among male rhesus monkeys while allowing the development of a shortened but otherwise normal skeleton.

Standard laboratory monkey diets have significantly higher calcium and vitamin D concentrations than do typical American human diets. Consequently, “age-associated” reductions in vitamin D status and the hyperparathyroidism commonly observed in humans were not found in postmenopausal rhesus females (Champ and Brinkley, 1996). Although bone-mineral turnover was increased in the rhesus females, there was no observed difference in bone density as measured with DEXA absorptiometry at the lumbar spine and distal radius.

Immunology

After 7 years, several immunologic measures were evaluated in the NIA monkeys. As in diet-restricted mice, lymphopenia was observed in diet-restricted monkeys, and peripheral blood lymphocyte numbers were significantly (P < 0.05) reduced compared with those in ad libitum-fed, age-adjusted controls (Weindruch et al., 1997). At the Wisconsin Regional Primate Research Center, reduced immune responses were reported (Roecker et al., 1996) in rhesus monkeys that were first subjected to dietary restriction as adults in 1989. After 2-4 years of dietary restriction, natural killer cell activity, antibody responses to influenza vaccine, and responses to concanavalin A and pokeweed mitogens were reduced (P < 0.01) compared to ad libitum-fed controls.

Wound Healing

Wound healing has been observed to become increasingly impaired with advancing age in various species (Roth et al., 1997). Concentrations of the glycation product pentosidine increase in skin collagen during aging at rates inversely proportional to life span in a large variety of mammalian species. Pentosidine accumulation is retarded



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement