Effect of age and osteoarthritis on bone mineral in rhesus monkey vertebrae.

We have used vertebrae of free-ranging rhesus macaques to study the effect of age and osteoarthritis on bone mineralization and bone density and to relate these findings to weight, sex, parity, and mineral chemistry. Bone mineralization was determined using the density fractionation technique and bone density using dual-photon absorptiometry. Arthritis was determined osteologically. We found a relationship between mineralization, age, and osteophytes, such that mineralization rose with age in nonarthritics and decreased with age in arthritics. This could also be seen when the females were examined separately. In males, only an increase in mineralization with age could be seen. In females mineralization decreases with parity. Also in females, DPA density decreases with age and increases with parity. No relationships with DPA density could be seen using males and females together or males alone. In conclusion, we have shown that normal skeletal aging in rhesus monkeys is accompanied by an increase in mineralization similar to that in other species, but this is not true in the presence of osteoarthritis. In the females parity has an important effect because it seems to build up bone mass even though the bone present may be undermineralized.

Directional asymmetry in the forelimb of Macaca mulatta.

Asymmetry was investigated in the forelimbs of 150 rhesus monkey (Macaca mulatta) skeletons using measurements of right and left humerii, radii, ulnae, second metacarpals, and femora. Seven of the ten forelimb dimensions were larger on the right than on the left side. Paired t-tests revealed that the mean of the right side was significantly larger than that for the left for two measurements of the ulna and two of the humerus. No measurement was significantly larger on the left than on the right side. These results indicate a small but significant asymmetry in the forelimb bones of rhesus monkeys and, as is the case for humans, the direction of asymmetry favors the right side. Our findings are consistent with an interpretation of hypertrophy of certain muscles and opens the question of whether rhesus monkeys preferentially use their right forelimbs for manipulative tasks that require manual dexterity, as is the case for humans. These forelimb skeletal asymmetries are discussed in light of the recent literature on cortical asymmetry and handedness in nonhuman primates.

Ocular development and aging. 1. Corneal endothelial changes in cats and in free-ranging and caged rhesus monkeys.

The endothelium of the cornea is said to retain its cellular proliferative capacity in rabbits but not in cats or primates. The present study was undertaken to determine whether the decline in cell density with increasing age is shared by all species that presumably lose their corneal endothelial-cell proliferative capacity and to determine whether in primates age-dependent changes in the endothelium are influenced by such environmental factors as light intensity and temperature. We found that in cats a very rapid decline in endothelial cell density during the first 10 months post partum was followed by a slower decline between 10 and 12 months, corresponding to a rapid increase followed by a slower rate of increase in corneal surface area. Between 1- and 14 years of age, a further decline in endothelial-cell density did not occur, and no endothelial pleomorphism or corneal guttata was observed among the 44 cats studied in this age group. In rhesus monkeys, an approximate 20% decline in cell density between 1 and 6 years of age, representing a period of ocular growth, was followed by a continuing decline in endothelial cell density at a slower rate of 0.7 to 0.8% per year throughout the rest of the lifespan, despite the fact that there was no evidence for further increase in globe size during this period of adulthood and aging. This rate of decline is similar to that described in the human corneal endothelium and was found to be the same in free-ranging animals continually exposed to high levels of solar radiation and in animals caged under artificial room light of much lower intensity and a year-round temperature of 21 +/- 1 degrees C. However, the animals maintained indoors showed a much higher frequency of endothelial pleomorphism than the free-ranging animals. These differences in age-dependent changes between feline and primate corneal endothelium and between primates living under grossly different environmental conditions are discussed.

Ontogenetic plasticity in nonhuman primates: I. Secular trends in the Cayo Santiago macaques.

Although secular trends toward increasing body size are apparent in many human populations, little is known about their occurrence in nonhuman primates. The Cayo Santiago skeletal collection of Macaca mulatta includes 101 adult animals (greater than or equal to 10 years of age) born at different times in the past 3 1/2 decades, so that variation in size may be examined relative to birth year. No secular trends in orbital height were observed in this sample, but in both sexes lengths of adult long bones increased significantly over time, while cranial dimensions and length of the second molar in female also showed significant variation with birth year. These changes were consistent with the history of provisioning of the animals and with fluctuations in population size. Low-order correlations were observed between birth year and body proportions, especially the crural index in males, a pattern that has also been observed in human populations. These findings argue that, in addition to biomechanics and heritage, diet may affect allometric relationships and that an inherent plasticity or malleability of the growth process may be characteristic of nonhuman as well as human primates.

Slit-lamp studies of the rhesus monkey eye. I. Survey of the anterior segment.

Slit-lamp photographic studies of 144 caged rhesus monkeys, aged 2 months to 35 years, show age-related changes in anterior-chamber depth, lens thickness, anterior and posterior curvatures of the lens, and location of the posterior lens surface relative to the anterior corneal surface. For these parameters, as well as for those measured by other techniques, a difference in slope magnitude and (or) slope sign was found between the growth phase which lasts for 5-6 years, and the adult phase (greater than 5-6 years). Age-related changes in the adult rhesus eye are qualitatively similar in almost all aspects to those observed in the human eye, indicating that the rhesus is a good animal model for the study of human loss of accommodative amplitude.

Presbyopia: an animal model and experimental approaches for the study of the mechanism of accommodation and ocular ageing.

During the last hundred years, observations on normal and a few aniridic human eyes, together with population studies on the age-dependent decline in accommodative amplitude, resulted in the formulation of theories of human accommodation, and led to the concept that presbyopia is an inevitable consequence of ageing. However, such studies failed to substantiate these theories and concepts or to reveal the fundamental mechanisms of accommodation and its age-dependent loss. Detailed understanding of these mechanisms and the environmental, dietary, and behavioural factors that may influence the development of presbyopia will require controlled studies and, in some cases, invasive experimental manipulations that can only be achieved through the use of an animal model. This paper reviews some of the evidence indicating that the rhesus monkey is a highly suitable primary animal model for such studies, as well as for studies on other aspects of ocular ageing, and reviews some of the techniques and experimental approaches that have already been adapted or developed for such studies.

Aging in the musculoskeletal system of rhesus monkeys: III. Bone loss.

It is well established that aging of the human skeleton includes the loss of bone mass or density, but little comparative information on age-related osteopenia in other primates is available. In order to determine whether bone loss occurs in normally locomoting nonhuman primates, radiographs of 139 rhesus monkey skeletons from the Cayo Santiago collection were examined, and measures of percent cortical bone (PCT) at the midshaft of second metacarpals, humeri, and femora were calculated. An age-related osteopenia was observed in the metacarpal of adult female macaques, although much individual variation was present. This variability could not be explained by reproductive history (number of offspring), matrilineal affiliation, or degree of osteoarthrosis. However, in a subsample of 15 animals, females who had given birth in the three months prior to death showed lower PCTs than those who had not conceived in the previous mating season. In adult males, PCT did not vary significantly with age, but males that weighed less and those with no/little osteoarthrosis showed lower PCTs than heavier or more arthritic animals, respectively. The multifactorial nature of the variation in PCT observed here suggests that similar processes of bone behavior are involved in the skeletal aging of both humans and rhesus monkeys.

Aging in the musculoskeletal system of rhesus monkeys: II. Degenerative joint disease.

In order to discuss the rate and onset of adult aging in rhesus monkeys, 55 adult animals from the Wisconsin Regional Primate Research Center and the University of Wisconsin Psychology Primate Laboratory were examined. Degenerative joint disease (DJD) at the hip and spine was scored, and loss of passive joint mobility at the hip was measured. Development of DJD at both the hip and spine was significantly and positively correlated with age. Spinal changes, especially at the thoraco/lumbar intervertebral symphyses, appeared to develop somewhat more rapidly than hip degeneration. In some individuals, DJD was observed soon after the completion of growth, but pronounced changes seldom occurred before the middle of the second decade of life. Similarly, age-dependent losses of passive joint mobility appeared to begin early in ontogeny and to become increasingly pronounced in the aging adult. Although interspecific comparisons are difficult due to intraspecies and intraindividual variation, the timing of musculoskeletal aging in the rhesus spine and hip differs from that observed in humans in a way that parallels previously documented species differences in patterns of musculoskeletal growth. These observations and data on age-related change in other systems, suggest that rates and durations of many ontogenetic processes in rhesus monkeys are approximately three times as fast and one-third as long as those of the corresponding human processes. Importantly, differences in the timing of reproduction do not appear to follow the same scaling factor observed in other systems. Although reproduction may, therefore, be under separate control, the consistent pattern observed in other aspects of somatic growth and aging supports the hypothesis (Cutler, 1976; Sacher, 1978) that evolutionary changes in ontogeny have resulted from selection acting upon a few genes with widespread regulatory effects.

Aging in the musculoskeletal system of rhesus monkeys: I. Passive joint excursion.

In order to describe ontogenetic change in the musculoskeletal system of rhesus monkeys, 126 Macaca mulatta from Cayo Santiago, ranging in age from 7 months to 21 years, were examined under anesthesia. Passive joint excursions were measured at the wrist, elbow, shoulder, hip, and knee. Mean ranges of excursion at these joints differed significantly between age groups and by sex. The potential for most movements appeared to decrease approximately 25 degrees over the first two decades of the macaque life span, and males generally showed less potential for movement than females in all age groups. These results are similar to those obtained for humans and are consistent with patterns of positional behavior, trauma, and osteoarthritis observed in this rhesus monkey population. Thus, to fully describe the locomotor strategy of rhesus monkeys, age- and sex-related variation in locomotor anatomy and functional capacity must be considered.

Vertebral pathology in the afar australopithecines.

Ten vertebral elements from the AL-288 partial hominid skeleton and 11 elements from the AL-333 collection are described. The AL-288 column presents a marked kyphosis at the level of thoracic vertebrae 6 through 10, with pronounced new bone formation on the ventral surfaces of these vertebrae. These features, associated with narrowed disc space and minor osteophytosis, resemble Scheuermann disease in the human. Even though this diagnosis is consistent with a basically human, bipedal locomotor repertoire, the presence of Scheuermann disease suggests that lifting, climbing, or acrobatic activities may have been important in early hominids.

Age-dependent loss of accommodative amplitude in rhesus monkeys: an animal model for presbyopia.

The refractive power and axial dimensions of the eye were measured under resting and fully accommodated conditions in 123 caged rhesus monkeys ranging in age from 0.5 to greater than 30 years. The mean resting refraction measured under ketamine anesthesia was -5 diopters. Accommodative amplitude, calculated as the difference between resting refraction and the most negative refraction measured 0.5 to 1 hr after topical application of a maximally effective dose of a cholinomimetic, showed an age-dependent decline. The mean accommodative amplitude of 1- to 5-year-old rhesus monkeys was a remarkable 34 D, while animals over 25 years of age averaged 5 D of accommodation. Some greater than 25-year-old animals showed no measurable change in refraction regardless of the dose or the type of cholinomimetic (carbachol, pilocarpine, or echothiophate) used. The resting axial thickness of the lens was found to increase with age throughout adulthood, well past the end of the growth period. A strong correlation was found between pharmacologically induced change in the refractive power of the eye and change in lenticular thickness. These similarities to the human condition suggest that the rhesus monkey represents a highly suitable animal model for the study of accommodation and presbyopia.

The development of presbyopia in primates.

Presbyopia, the age-dependent decline in accommodative amplitude, clinically afflicts every individual reaching the age of 40 to 45 years. Various pathophysiologic mechanisms have been proposed, but none is proven, and until now no animal model for their study has existed. Refraction, axial dimensions, and pharmacologically-induced accommodation were determined in caged rhesus monkeys aged 0.5 to 32 years. Accommodative amplitude decline in an age-dependent manner from greater than 40 diopters to 0 diopters. Mean accommodative amplitude in 0.5 to 5-year old animals was 34.4 diopters; in greater than 25-year old animals it was 5 diopters. Considering the relative life expectancy and accommodative amplitude of rhesus and human, the rate of the age-dependent decline in accommodation was remarkably similar in the two species, as were the relationships between resting axial lenticular thickness and age, and between drug-induced accommodative amplitude and change in lenticular thickness. Thus, the rhesus monkey appears to provide the first known animal model for the study of accommodation and presbyopia as they occur in the human.

Intraocular pressure of rhesus monkey (Macaca mulatta). I. An initial survey of two free-breeding colonies.

As part of an ophthalmic and anthropometric survey of two free-breeding rhesus monkey (Macaca mulatta) populations, intraocular pressure (IOP) of 114 animals was measured under ketamine catalepsia with the use of a floating-tip pneumatonometer. The mean IOP of the 102 animals included in the main analyses was 14.9 +/- 2.1 (S.D.) mm Hg. The age distribution of animals in this sample ranged from 7 months to 21 years and reflected reasonably well the estimated age distribution in the total population (approximately 1600 macaques). Since ketamine does not have a barbiturate-like effect on IOP, this value can be regarded as a good estimate of the normal IOP of rhesus monkeys. No significant differences were found between left and right eyes nor between males and females. However, the mean IOP of infants and juveniles (7 months to 3 years) was significantly higher (15.7 +/- 2.0 mm Hg; n = 33) than that of young adult and adult rhesus monkeys (14.5 +/- 2.0; n = 69). The IOP of young animals (less than or equal to 6 years) showed a decline between 9 A.M. and 2 P.M., whereas the IOPs of older animals showed only small fluctuations between 8 A.M. and 5 P.M. This study shows that the normal IOP of macaques is remarkably similar to that of humans and demonstrates the fesibility of surveying IOP in free-ranging primates.