Therapeutic plasma exchange (TPE) and blood products – Implications for longevity and disease

People worldwide are living longer. According to the World Health Organization, by 2050 the world’s population aged 60 or older is ex- pected to total 2 billion, up from 900 million in 2015. Although longer

The authors conclude that the multiple, favorable structural and molecular properties of albumin, as well as its numerous pleiotropic physiologic functions (e.g. circulating

life brings personal, familial, and societal opportunities, older age is

A-beta binding capacity, antioxidant, immunomodulatory, anti-

associated with a number of physical and mental disorders. Age related diseases are the leading cause of death and healthcare costs. Reducing the rate of aging would have enormous medical and financial benefits. Heterochronic parabiosis models in mice (two animals sharing cir- culatory systems) have demonstrated that exposure of the aged pro-

genitor cells to the blood of the young partner results in proliferation and regenerative capacity of multiple tissues [1–5]. The interpretation of these findings was that the aging process may be slowed and even

reversed. It was suggested that certain proteins in young plasma were responsible for the observed rejuvenation. Candidates included GDF11,

B2M, CELII and TIMP2 [6–13]. But, none of those, nor the infusion of

young plasma have proven in clinical trials to be effective in improving health or rejuvenating tissues [14]. In fact, the infusion of plasma is associated with various adverse reactions, some life threatening, as pointed out in one of the papers in this section. This prompted the FDA to issue a warning to establishments that offered false claims of health benefits and antibody properties from infusion with plasma from young donors [15].

A couple of recent studies by the same investigators whose original experiments suggested that heterochronic parabiosis has an effect on the aging process demonstrated that young blood is not the primary deter- minant. They found that the dilution of old blood plasma yields a robust resetting of the systemic signaling milieu to youth and health, rejuve- nating multiple tissues [16]. In this section, the authors and their col- laborators discuss the translation of the mouse experiments to human clinical trials based on a previously published hypothesis [17].

One of the most common diseases associated with aging is Alz- heimer’s Disease (AD). In the United States 10 % of people aged 65 and

older suffer from AD and it is the fifth most common cause of death in individuals over 65 years of age. In this section, Costa and Paez discuss the pathophysiology of AD and report on the successful outcomes of a large, (347 patients) multicenter, randomized patient and physician blinded, placebo-controlled trial of TPE and intravenous immunoglob- ulin (IVIG) in AD. Albumin was used as a replacement fluid. Remark- ably, 90 % of 4,709 TPE procedures were without any adverse reactions. Results after 14 months of treatment showed a slower decline or stabi- lization of disease symptoms in AD patients with moderately severe disease compared to the placebo group. All patients with mild AD showed no decline at all and patients in the treatment group experienced clinical improvement. Of interest is that patients who were treated with TPE and IVIG had better response then those treated with TPE alone.

inflammatory), administered via TPE, is a powerful multi-targeted therapeutic approach for treating AD.

Since TPE with albumin was also used in the rejuvenation study, it raises a number of interesting questions: 1) Does the albumin binding capacity enhance the dilution of factors contributing to aging from old plasma? 2) Is it possible that albumin is the plasma protein that remains the subject of huge investment and research effort in the business of anti- aging? [18]

At this time, we can conclude that TPE with albumin appears to be a promising therapeutic approach for healthspan extension and the treatment of age related diseases such as AD.

As Mehdipour, et al. conclude: Aging results in a near endless list of systemic changes on tissues, cellular and molecular levels and multiple methods of therapeutics will be required to address these alternatives. More research is clearly needed to develop and explore the applications of rejuvenetive TPE alone or in combination with other therapeutics.

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References

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nation of aged progenitor cells by exposure to a young systemic environment. Nature 2005;433:750–4. https://doi.org/10.1038/nature03260.

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muscle. Cell Cycle 2005;4:407–10. https://doi.org/10.4161/cc4.3.1518.

3. Conboy MJ, Conboy IM, Rando TA. Heterochronic parabiosis: historical perspec- tive and methodological considerations for studies of aging and longevity. Aging

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aging and rejuvenation. Aging (Albany NY) 2015;7:754–65.

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Systemic attenuation of the TGFβ pathway by a single drug simultaneously re- juvenates hippocampal neurogenesis and myogenesis in the same old mammal. Oncotarget 2015;6:11959–78. https://doi.org/10.18632/oncotarget.3851.

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https://doi.org/10.1016/j.transci.2021.103163

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Available online 21 May 2021

1473-0502/© 2021 Elsevier Ltd. All rights reserved.

Guest Editorial

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Human umbilical cord plasma proteins revitalize hippocampal function in aged mice. Nature 2017;544:488–92. https://doi.org/10.1038/nature22067.

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endothelial cell VCAM1. Nat Med 2019;25:988–1000. https://doi.org/10.1038/

s4159-019-0440-4.

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symptom amelioration study: a randomized clinical trial. JAMA Neurol 2019;76: 35–40. https://doi.org/10.1001/jammaneurol.2018.3288.

15. Kaiser J. Antiaging trial using young blood stirs concerns. Science 2016;353(6299): 527–8. https://doi.org/10.1126/science.353.6299.527.

Transfusion and Apheresis Science 60 (2021) 103163

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three germ layers tissues by exchanging old blood plasma with saline-albumin. Aging (Albany NY) 2020;12:8790–819. https://doi.org/10.18632/aging.103418.

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cellular senescence—a hypothesis. J Clin Apher 2013;28:387–9. https://doi.org/ 10.1002/jca.21286.

18. De Magalaes JP, Stevens M, Thornton D. The business of anti-aging science. Trends Biotechnol   2017;35:1062–70.   https://doi.org/10.1016/j.tibtech.2017.07.004. 2017 the Authors.

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Dobri Kiprov

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E-mail address: dkiprovcai@aol.com.