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

Abstract

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.

Fig. 1

Illustrations of stages of the parabiosis surgery. Following all the requisite surgical preparations and shaving of the skin along the flanks of mice to be joined (A), a skin incision is made along the opposing flanks of each mouse (B). The skin is freed from the underlying peritoneal lining of each skin flap (C), being careful not to damage the peritoneum. With the mice side-by-side in a prone position, the dorsal skin flaps from the two mice are pinched together and stapled in a rostral-to-caudal fashion (D), until the dorsal flaps are stably joined (E). The connection is secured by suturing the corresponding joints (elbows and knees), using a suture passed through the soft tissues of each joint while avoiding passing through the joints themselves (F). With the pair flipped over to reveal the ventral skin flaps (G), the process of stapling the skin and suturing the joints is repeated, resulting in the generation of stable parabionts (H) (illustrations are adapted from photographs in Conboy & Conboy, 2009).