The marmoset as a model of aging and age-related diseases

Abstract

The common marmoset (Callithrix jacchus) is poised to become a standard nonhuman primate aging model. With an average lifespan of 5 to 7 years and a maximum lifespan of 16½ years, marmosets are the shortest-lived anthropoid primates. They display age-related changes in pathologies that mirror those seen in humans, such as cancer, amyloidosis, diabetes, and chronic renal disease. They also display predictable age-related differences in lean mass, calf circumference, circulating albumin, hemoglobin, and hematocrit. Features of spontaneous sensory and neurodegenerative change--for example, reduced neurogenesis, ß-amyloid deposition in the cerebral cortex, loss of calbindin D(28k) binding, and evidence of presbycusis--appear between the ages of 7 and 10 years. Variation among colonies in the age at which neurodegenerative change occurs suggests the interesting possibility that marmosets could be specifically managed to produce earlier versus later occurrence of degenerative conditions associated with differing rates of damage accumulation. In addition to the established value of the marmoset as a model of age-related neurodegenerative change, this primate can serve as a model of the integrated effects of aging and obesity on metabolic dysfunction, as it displays evidence of such dysfunction associated with high body weight as early as 6 to 8 years of age.

Figure 1

Survival analysis of 358 marmosets (Callithrix jacchus) that were born at the Southwest National Primate Research Center (SNPRC) colony and survived at least 6 months, between January 1994 and March 2010, excluding individuals whose deaths were related to experiments. Figure 1A illustrates survival by age; Figure 1B illustrates age-specific mortality.

Figure 2

Causes of mortality for the New England Primate Research Center population of marmosets (Callithrix jacchus), January 2004 to June 2009. (A) Less than 5.78 years of age; (B) more than 5.78 years of age; (C) more than 10 years of age. n = 77; animals in 2C are included in 2B. IBD, inflammatory bowel disease; open = no cause of death identified; iatrogenic = death from a complication associated with anesthesia or treatment. Unlabeled slivers represent causes of mortality (injury in (B) and injury and iatrogenic in (C)) that occurred in less than 1% of the animals.

Figure 3

(A) Relation of fat-free mass (FFM) to age in a cross-sectional study of 20 marmosets (Callithrix jacchus), as reported by Power and colleagues (2001). (B) Relation of weight to age in years for marmosets surviving less than 4 years (in red), 4 to 8 years (in green), and more than 8 years (in purple). (C) Relation of peak weight to survival.

Figure 4

Change in strength of distortion product otoacoustic emissions (OAE) with age. For a marmoset with normal hearing the OAE response strength curve, as a function of stimulation frequency, should look similar to the averages over many marmosets (n = 10) for the left and right ears (panels C, D, black lines). The blue line represents noise levels in the system; OAE response is significant if the measured strength exceeds (lies above) the noise curve. In the case of a young female (A) the emission strength was somewhat better than the group average; it remained high for frequencies up to about 12 kHz and declined thereafter. In contrast, for an old male (B) response strength declined as frequency increased, demonstrating a possible sloping hearing loss that is similar to that in humans. At frequencies above 10 kHz it approached the noise level, suggesting that no emissions were present. f2 denotes the high-frequency tone in the two-tone complex used to elicit an OAE; SPL, sound pressure level measured in decibels (dB, 20 µPa).

Figure 5

Fasting insulin concentrations in a population of 31 female marmosets (Callithrix jacchus). (A) Relation of insulin concentration to age. (B) Relation of insulin concentration to body weight. (C) Insulin concentration in young (<5 years of age) and old (5 to 8 years of age) marmosets, limited to animals >400 g in weight (n = 11).