Heterochronic parabiosis: historical perspective and methodological considerations for studies of aging and longevity

Abstract

Summary Pairing two animals in parabiosis to test for systemic or circulatory factors from one animal affecting the other animal has been used in scientific studies for at least 150 years. These studies have led to advances in fields as diverse as endocrinology, immunology, and oncology. A variation on the technique, heterochronic parabiosis, whereby two animals of different ages are joined to test for systemic regulators of aspects of aging or age-related diseases also has almost a century-long scientific history. In this review, we focus on the history of heterochronic parabiosis, methodological considerations and caveats, and the major advances that have emerged from those studies, including recent advances in our understanding of stem cell aging.

Improving the Post-Stroke Therapeutic Potency of Mesenchymal Multipotent Stromal Cells by Cocultivation With Cortical Neurons: The Role of Crosstalk Between Cells

“…Attempts to track the mechanisms of such interorgan signal transmission have been made using parabiosis, an experimental model in which the circulatory systems of animals of the same or different age (homochronic or heterochronic systems, respectively) were united [46]. In particular, it was found that heterochronic parabiosis enhances the proliferation of neural stem cells in older animals and that these neural stem cells differentiated into neuroblasts and migrated to the olfactory bulb, resulting in a significant increase in the discrimination of smell [47].…”

Extracellular vesicles and aging

“…However, it is also clear from heterochronic parabiosis (12)(13)(14)(15)(16)(17) and serum transfer (17,18) studies that cell non-autonomous mechanisms play important roles in suppressing or driving degenerative changes that arise as the consequence of spontaneous, stochastic damage. For example, using heterochronic parabiosis, it was demonstrated that factors in young blood rejuvenate certain cell types and tissues in old mice (12)(13)(14)(15)(16)(17). These anti-geronic factors in young serum include GDF-11 and oxytocin (19).…”

Lack of evidence for GDF 11 as a rejuvenator of aged skeletal muscle satellite cells

“…Numerous reports have demonstrated the existence of factors present in the circulatory system of young rodents that can promote tissue regeneration in aged rodents (Lunsford et al ., 1963; Conboy et al ., 2005; Conboy et al ., 2013). GDF11 was recently proposed to decline in concentration in old mice and to restore young tissue function phenotypes in the heart, CNS, and skeletal muscle (Loffredo et al ., 2013; Sinha et al ., 2014).…”