Debate continues over the mechanisms responsible for the outcomes observed in parabiosis studies, in which a young and an old individual have their circulatory systems linked. The young individual shows a decline in measures of health, while the old individual shows an improvement - a modest reversal in some aspects of aging. That there must be harmful factors in old blood seems a solid conclusion, but are benefits to the older individual mediated by the presence of beneficial factors in young blood, or by dilution of harmful factors in old blood? There is evidence for both sides. Here, researchers outline some of the support for eotaxin-1 to be one of the harmful factors present in larger amounts in the bloodstream of older individuals, and consider possible implications for the blood transfusion industry.
High blood levels of the chemokine eotaxin-1 (CCL11) have recently been associated with aging and dementia, as well as impaired memory and learning in humans. Importantly, eotaxin-1 was shown to pass the blood-brain-barrier (BBB) and has been identified as crucial mediator of decreased neurogenesis and cognitive impairment in young mice after being surgically connected to the vessel system of old animals in a parabiosis model. It thus has to be assumed that differences in eotaxin-1 levels between blood donors and recipients might influence cognitive functions also in humans. However, it is unknown if eotaxin-1 is stable during processing and storage of transfusion blood components.
In this study, we show for the first time that ready-to-use transfusion blood components contain CCL11 at a physiological concentration. Importantly, in both blood components eotaxin-1 expression did not differ between males and females, but significantly increased with the donor's age in both sexes. Of note, eotaxin-1 levels detected in these processed, transfusible blood products are comparable with those found in unprocessed plasma of healthy individuals. We demonstrated that eotaxin-1 is subject to only minor donor-specific changes over 15 measurements within a 3-months period of time, even when samples have been taken at different times of day. Taken together, our findings and the available literature prove that eotaxin-1 is a relatively stable factor in fresh or processed blood components of one individual over a longer period of time, but significantly rises with increasing age.
Eotaxin-1 was found increased in Alzheimer's disease patients compared to age-matched controls. Eotaxin-1 correlated with impaired verbal and visual memory, and other conditions associated with cognitive decline, such as recurrent depression have also been associated with increased levels of the chemokine. Moreover, it was demonstrated that, among a range of cytokines and chemokines, eotaxin-1 correlated most strongly with reduced hippocampal neurogenesis and aging in mice, and importantly, artificially increasing eotaxin-1 levels in young mice resulted in decreased neurogenesis as well as in impaired memory and learning. Using mouse parabiosis models further proved that exposure of a young animal to the systemic milieu of an older mouse is sufficient to induce severe cognitive impairments and reduced neurogenesis after 2-5 weeks, and identify blood-borne eotaxin-1 as one of the responsible factors.
It has to be considered that a direct impact of short-term eotaxin-1 exposure on neurogenesis and mental factors has only been assessed in mice so far. It is unclear whether a single transfusion of high-eotaxin-1 containing blood components to recipients with very low levels will indeed change total eotaxin-1 levels in the recipient, if this elevation is transient or durable, and if it does indeed influence cognitive functions in humans. Future studies require a prospective study design to carefully resolve these questions.