Fight Aging!

The use of animals in the study of aging has always meant striking a balance between species life span and distance from humans in the evolutionary tree of life. Very short-lived species such as worms and flies allow for much cheaper, faster studies, but the biochemistry of these species is more distant from ours, meaning fewer of the results are relevant to human medicine. Fortunately many of the fundamental processes of aging are near universal in animal life, all the way down to yeast colonies, so it is possible to perform useful exploratory research at a reasonable price. Still, researchers are ever in search of a better class of animal, one that has a much greater similarity to humans without the very lengthy life span. Even using short-lived mammals such as mice, that live for a few years, results in studies that are expensive and long-running when considered as a fraction of the length of a career, or placed against the size of most grants. Further, even mice have sometimes meaningful differences when compared with humans, such as their telomere dynamics. If large amounts of time and money are to be spent, then researchers would ideally want to run studies of aging in primates, and this has happened for decades-long studies of calorie restriction in rhesus macaques. Such studies are highly unlikely to happen again in the foreseeable future, however, given a broad dissatisfaction with the planning and outcomes of these examples. Researchers have started to look at the small selection of comparatively short-lived primates instead, and currently there is a faction advocating the use of marmosets:

Great leaps forward in our understanding of the basic biology of aging, including interventions that extend longevity, have come about from using common laboratory animal models. As we now strive to apply these findings for human benefit, a serious concern arises in how much of this research will directly translate to normal, largely healthy, and genetically varied populations of people. Laboratory animals, including rodents, are only distantly related to humans and have undergone different evolutionary pressures that likely have driven species-specific idiosyncrasies of aging. Due to our long lifespans, any outcomes of longevity interventions in human studies are unlikely to be discovered even during the research careers of current graduate students. There is then strong rationale for testing whether the interventions discovered that slow aging in laboratory rodents, such as dietary restriction, mTOR (mechanistic target of rapamycin) inhibition, or acarbose, will also extend the lifespan of species more closely related to humans. In this context, the calorie restriction studies utilizing non-human primates are prime examples of this approach. However, the rhesus macaques used in these studies also have relatively long lifespans which required time commitment in the order of decades to accomplish the recently published final results.

Most non-human primates that can be kept in healthy laboratory populations have relatively long lifespans, but the small South American common marmoset (Callithrix jacchus) may offer a number of advantages over other non-human primate species, particularly for researchers interested in aging. The normal lifespan of the common marmoset is the shortest of any anthropoid primate, with an average lifespan in captivity of approximately 7-8 years and maximum lifespans reported between 16 and 21 years. While much longer-lived than rodents, the average age of marmosets is more manageable for a designed longevity study than the 25-year average lifespan of rhesus macaques or the 70-plus average lifespan of humans. In addition, marmosets in a closed colony have a natural adult mortality that drives a decline in their cumulative survival rate from about 85 to 35% that occurs between 5 and 10 years of age. In other words, a carefully designed intervention study could occur over the time course of a single NIH RO1 granting period using this non-human primate.

Similar to other non-human primates, the sequenced marmoset genome has high homology (more than 93%) with that of humans. Many of the common molecular biology tools, including antibodies, have relatively good cross-species recognition. Marmosets have a growing track record as a non-human primate model used for a number of diseases and pathologies that are generally considered as age-related, including Parkinson's disease, respiratory diseases, and infectious diseases. Moreover, marmosets display age-related changes in pathologies associated with diabetes, cardiac disease, cancer, and renal disease similar to those seen in humans. Marmosets thus represent a complement to the existing non-human primate models used to study aging and, in particular, a model in which effects on longevity might be assessed in a relatively timely manner. Despite this promising outlook, there are some potential challenges to using the common marmoset as a non-human primate model to study aging. Like other non-human primates, there is much less genetic tractability in this species relative to the mouse, which must be taken into account when designing studies on the biology of aging. However, transgenic marmosets have been previously generated and new technologies including CRISPR/Cas systems may lead the way in developing new, genetically modified marmoset models for the study of age-related diseases or the basic biology of aging.

Link: http://dx.doi.org/10.3402/pba.v6.32758