A pair of publications in Science attempt to address the often-controversial topic of the rejuvenating, or regenerative, effects of tissues/fluids derived from young organisms on their older counterparts. Specifically, experiments in mice have shown that blood from young mice has a rejuvenating effect on older mice. The pair of studies tackle questions such as exactly which blood component is responsible for the rejuvenating effects and exactly what some of those rejuvenating effects are. Both studies identify the circulating protein growth differentiation factor 11 (GDF11), a member of the transforming growth factor-β (TGF-β) family, as being at least one of the agents responsible for the beneficial effects.
In the Katsimpardi article,* the team demonstrated that application of recombinant GDF11 protein (rGDF11), accomplished by injecting 22-month-old mice with rGDF11 for 4 weeks, promoted remodeling of the aged cerebral vasculature, leading to an improvement of blood flow, and activation of subventricular zone neural stem cell proliferation, which in turn resulted in an improved olfactory function (Figure 1).
In the Sinha study,** a similar treatment of aged mice with recombinant GDF11 resulted in improvements of myofibrillar and mitochondrial morphology, as revealed by electron microscopy, as well as improvements in muscle performance parameters (Figure 2).
While the exact mechanisms by which GDF11 causes “rejuvenation” of the circulatory and musculoskeletal system remain to be delineated, the present reports highlight the possibility of treating a range of genetic conditions, as well as diseases of “old age,” through GDF11 supplementation either via direct application of recombinant protein or by gene therapy means.
*Abstract from Science 2014, Vol. 344: 630–634
In the adult central nervous system, the vasculature of the neurogenic niche regulates neural stem cell behavior by providing circulating and secreted factors. Age-related decline of neurogenesis and cognitive function is associated with reduced blood flow and decreased numbers of neural stem cells. Therefore, restoring the functionality of the niche should counteract some of the negative effects of aging. We show that factors found in young blood induce vascular remodeling, culminating in increased neurogenesis and improved olfactory discrimination in aging mice. Further, we show that GDF11 alone can improve the cerebral vasculature and enhance neurogenesis. The identification of factors that slow the age-dependent deterioration of the neurogenic niche in mice may constitute the basis for new methods of treating age-related neurodegenerative and neurovascular diseases.
**Abstract from Science 2014, Vol. 344: 649–652
Parabiosis experiments indicate that impaired regeneration in aged mice is reversible by exposure to a young circulation, suggesting that young blood contains humoral “rejuvenating” factors that can restore regenerative function. Here, we demonstrate that the circulating protein growth differentiation factor 11 (GDF11) is a rejuvenating factor for skeletal muscle. Supplementation of systemic GDF11 levels, which normally decline with age, by heterochronic parabiosis or systemic delivery of recombinant protein, reversed functional impairments and restored genomic integrity in aged muscle stem cells (satellite cells). Increased GDF11 levels in aged mice also improved muscle structural and functional features and increased strength and endurance exercise capacity. These data indicate that GDF11 systemically regulates muscle aging and may be therapeutically useful for reversing age-related skeletal muscle and stem cell dysfunction.