A lot of
the discussion on this forum recently has been around the modification of the
concentration of certain plasma factors in the elderly by transfusion of plasma
from young donors. This would result in the dilution of “over expressed”
factors and the supplementation of “under expressed” factors. It would also
involve risks such as allergic reactions to donor proteins.
volume of plasma for a 70kg human is about 2.8L. As the fraction of original
plasma remaining (y) can be calculated by the formula y= e-x, (where
x is the volume of donor plasma used), the “law of diminishing returns”
dictates that, after transfusion of about 3L of donor plasma, about 30% of
original plasma would still remain. Within about 24 hours, levels of “depleted
factors” will be replenished from interstitial fluid, which makes up about
10-12 L in a 70kg human (Ward, 2011).
transfusions may be needed to restore all factors to “youthful levels”. This
increases the risk of adverse reactions.
it possible to use a combination of oral supplementation and filtration of
plasma (autologous) to achieve a similar result without allergic (or viral transmission) risks?
Some of the
factors listed as declining with age can be orally ingested to boost plasma
levels. For example, melatonin, DHEA and
ubiquinone are easily available OTC.
and sex hormones are also available, but usually prescription only.
the over-abundant factors, some (such as NF-kB and CCL11/eotaxin) may be
inhibited by oral supplements. Others, such as IL-6 and MCP-1 could possibly be
lowered by filtration. Filtration technology of cytokines from the serum has
rapidly evolved. Using haemofiltration of 11.8L/day, van Bommel et al (1997)
were unable to reduce plasma levels of TNF-α, TNF-RI, TNF-RII and IL-Ra in 9
patients suffering from systemic inflammation response syndrome.
Vriese et al (1999) showed that inflammatory cytokines (and their inhibitors)
could be removed from the serum of 15 patients with septic shock and renal
failure. Cytokine removal was highest 1 hour after filtration started (with an
AN69 membrane) but decreased thereafter, indicating membrane saturation.
Lentz & Kumar demonstrated that plasma levels of soluble TFN-R1 and IL-2R could be lowered by an
immunosorption column in patients with metastatic cancer.
given the advances in antibodies and binding agents, even better results could
be obtained today?
et al (1999) J. Am. Soc. Nephrology 10(4): 846-853.
Kumar (2008) Therapeutic Apheresis 12(6): 491-498.
et al (1997) Renal Failure 19(3): 443-454.
(2011) Conventional Apheresis Therapies: A Review. J. Clin. Apheresis 26:
On Sun, Mar 8, 2015 at 5:50 PM, steve hill wrote:
Oh do tell Harold? What is the alternative to human donors? Animal Plasma?
From: Dr. Harold Katcher To: Mike Darwin ; Gerontology Research Group Sent: Sunday, 8 March 2015, 2:29
Subject: Re: [GRG] Plasma Factors and aging
What you say makes sense – if the work is done here. Also you can pay volunteers twice the market rate and pass the cost onto the customer – it still wouldn’t be anything near the cost of a new monoclonal antibody treatment or heart surgery – which it could replace. It requires no new technology and represent a means for money transfer from the old to the young – the young can give (even at much less frequency than plassers) to provide several people with plasma and be able to store a supply for themselves over the course of say four years. Well assuming it works – or can be made to work – what are the alternatives – well one the obvious one is to isolate all of the molecular species that constitute the age determining molecules and adjust their concentrations (including the concentrations of those ‘pro-aging’ molecules like the various pro-inflammatory factors like TNF, IL-6 etc. So it would seem, if that were needed, to require removal and replacement of plasma – assuming all the molecular species could be easily produced…. But we don’t know the species, and artificial production would be enormously more expensive than using plasma sold by disease-free youth (an impetus for them to remain so) – and provide both populations with a new life. I don’t see harm in that – but let me just say – experiments done so far reveal another potential path that would spare both people and cost (not that people are harmed in plasma exchange).