An Interesting Delivery Method for GDF11
GDF11 was one of the earliest allegedly beneficial factors identified in parabiosis experiments, in which young and old mice have their circulatory systems joined. Researchers saw higher levels of GDF11 in younger mice, and proposed that increased GDF11 signaling was a meaningful mechanism to explain the observed improvement in function of tissues in older mice. Following on from that, there has been considerable, continuing debate over whether or not this is in fact the case.
A company, Elevian, was founded to build GDF11-based therapies, and claims to have resolved much of that controversy. Still, later studies have demonstrated very convincingly that parabiosis benefits derive from a dilution of harmful circulating molecules in the circulation of old mice, rather than the delivery of beneficial molecules from young mice. It remains to be seen as to where this broad area of research will lead, an increased interest in plasma dilution and replacement of albumin are the latest developments.
Along the way, a few studies have suggested that delivery of recombinant GDF11 or upregulation of GDF11 expression can produce benefits in mice, such as reduced inflammatory signaling or other improvements in metabolism. Today's open access paper is a recent example. It is noteworthy for the delivery method used, which is quite intriguing. The researchers produced a yeast lineage that expresses GDF11, and fed the yeast to the mice in their diet, resulting in delivery of that GDF11 to the circulation. One might wonder how many other proteins would survive the oral administration route via this approach.
Since the discovery of GDF11 as a "youth factor", it has become a "hot" molecule in the field of anti-aging study. Yet there is still controversy over the age-related change in concentration of GDF11 and its role in the genesis of rejuvenation conditions. With the aid of a highly specific anti-GDF11 antibody, here we show that GDF11 concentration declines with age in male mice, confirming the results of ours and others that blood GDF11 abundance reduces with age in both fish and mouse as well as humans.
In this study, we displayed rGDF11 on the surface of the yeast Yarrowic Lipolytica, and proved the bioavailability of the yeast-displayed rGDF11 by oral delivery in aged male mice. On the basis of these findings, we started to explore the anti-aging activity and underlying mechanisms of displayed rGDF11. It was found that dietary intake of displayed rGDF11 had little influence on the body weight and biochemical parameters of aged male mice, but delayed the occurrence and development of age-related biomarkers such as lipofuscin and senescence-associated-β-galactosidase, and to some extent, prolonged the lifespan of aged male mice.
Moreover, we demonstrated once again that dietary intake of displayed rGDF11 enhanced the activity of anti-oxidant enzymes, including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX), reduced the reactive oxygen species (ROS) level, and slowed down the protein oxidation and lipid peroxidation. Importantly, we showed for the first time that rGDF11 enhanced the activity of CAT, SOD, and GPX through activation of the Smad2/3 signaling pathway. Our study also provided a simple and safe route for delivery of recombinant GDF11, facilitating its therapeutic application in the future.
wonder if a yeast lineage could be produced that expresses α-klotho?