Sporadic Premature Aging in a Japanese Monkey: A Primate Model for Progeria

Abstract

In our institute, we have recently found a child Japanese monkey who is characterized by deep wrinkles of the skin and cataract of bilateral eyes. Numbers of analyses were performed to identify symptoms representing different aspects of aging. In this monkey, the cell cycle of fibroblasts at early passage was significantly extended as compared to a normal control. Moreover, both the appearance of senescent cells and the deficiency in DNA repair were observed. Also, pathological examination showed that this monkey has poikiloderma with superficial telangiectasia, and biochemical assay confirmed that levels of HbA1c and urinary hyaluronan were higher than those of other (child, adult, and aged) monkey groups. Of particular interest was that our MRI analysis revealed expansion of the cerebral sulci and lateral ventricles probably due to shrinkage of the cerebral cortex and the hippocampus. In addition, the conduction velocity of a peripheral sensory but not motor nerve was lower than in adult and child monkeys, and as low as in aged monkeys. However, we could not detect any individual-unique mutations of known genes responsible for major progeroid syndromes. The present results indicate that the monkey suffers from a kind of progeria that is not necessarily typical to human progeroid syndromes.

Biomarkers to identify and isolate senescent cells

“…One of the major limitations of all these markers is the fact that the change is only (Herbig et al, 2006;Oishi et al, 2014), and (ii) their removal might be impaired due to declining efficiency of the immune system. These accumulating senescent cells can (iii) damage surrounding cells (Biran and Krizhanovsky, 2015) and cause (iv) cancer (Leikam et al, 2015) and (v) other agerelated diseases, such as atherosclerosis (Erusalimsky and Kurz, 2005;Fischer et al, 2013;Nishimatsu et al, 2015).…”

Derivation of induced pluripotent stem cells in Japanese macaque (Macaca fuscata)

“…To date, several spontaneous mutant monkeys have been found in the Japanese macaque populations. For example, a child monkey in our institute was characterized by significant premature aging that exhibited common symptoms with human progeria, including deep skin wrinkles, cataract, poikiloderma, and shrinkage of cerebral cortex 12 . To identify the genes associated with these phenotypes, genomic DNA sequencing of this monkey was performed.…”

“…The Japanese macaque also has attracted researcher’s attention in laboratories as a valuable experimental animal model due to their anatomical and physiological similarities to humans, their high cognitive ability, and their gentle and patient character 4 . Especially, the Japanese macaque has contributed to the advance of neuroscience 5 through the investigations of brain activity and cognition 6 – 9 , neural pathway and gene expression 10 , 11 , and spontaneous mutant monkeys 12 – 15 . From the above, the Japanese macaque has been employed as an excellent primate model with the accumulated knowledge and a potential to integrate the laboratory studies with the field research.…”

International Harmonization of Nomenclature and Diagnostic Criteria (INHAND): Non-proliferative and Proliferative Lesions of the Non-human Primate (<i>M. fascicularis</i>)

“…Congenital lens fiber degeneration (cataracts) in macaques has been attributed to genetic defects, in utero infectious agents, concurrent ocular developmental anomalies, or is of unknown origin 581 , 591 , 592 , 593 , 594 .…”