Re: [GRG] Plasma Factors and aging

Greetings,

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.

The average
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).

So, several
transfusions may be needed to restore all factors to “youthful levels”. This
increases the risk of adverse reactions.

 

However, is
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.

GDF-11, thyroxine
and sex hormones are also available, but usually prescription only.

 

Regarding
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.

However, De
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.

By 2008,
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.

 

Surely,
given the advances in antibodies and binding agents, even better results could
be obtained today?

 

Cheers.

References

 

De Vriese
et al (1999) J. Am. Soc. Nephrology 10(4): 846-853.

Lentz and
Kumar (2008) Therapeutic Apheresis 12(6): 491-498.

Van Bommel
et al (1997) Renal Failure 19(3): 443-454.

Ward, D.M.
(2011) Conventional Apheresis Therapies: A Review. J. Clin. Apheresis 26:
230-238.

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

Mike,
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).

Sincerely,

Harold

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About Johnny Adams

My full-time commitment is to slow and ultimately reverse age related functional decline to increase healthy years of life. I’ve been active in this area since the 1970s, steadily building skills and accomplishments. I have a good basic understanding of the science of aging, and have many skills that complement those of scientists so they can focus on science to advance our shared mission. Broad experience Top skills: administration, management, information technology (data and programming), communications, writing, marketing, market research and analysis, public speaking, forging ethical win-win outcomes among stakeholders (i.e. high level "selling"). Knowledge in grant writing, fundraising, finance. Like most skilled professionals, I’m best described as a guy who defines an end point, then figures out how to get there. I enjoy the conception, design, execution and successful completion of a grand plan. Executive Director Gerontology Research Group (GRG). Manages Email discussion forum, web site, meetings and oversees supercentenarian (oldest humans, 110+ years) research. CEO / Executive Director Carl I. Bourhenne Medical Research Foundation (Aging Intervention Foundation), an IRS approved 501(c)(3) nonprofit. http://www.AgingIntervention.org Early contributor to Supercentenarian Research Foundation. Co-Founder Geroscience Healthspan Forum. Active contributor to numerous initiatives to increase healthy years of life. Co-authored book on conventional, practical methods available today to slow the processes of aging – nutrition, exercise, behavior modification and motivation, stress reduction, proper supplementation, damage caused by improper programs, risk reduction and others. Fundamental understanding of, and experience in the genomics of longevity (internship analyzing and curating longevity gene papers). Biological and technical includes information technology, software development and computer programming, bioinformatics and protein informatics, online education, training programs, regulatory, clinical trials software, medical devices (CAT scanners and related), hospital electrical equipment testing program. Interpersonal skills – good communication, honest, well liked, works well in teams or alone. Real world experience collaborating in interdisciplinary teams in fast paced organizations. Uses technology to advance our shared mission. Education: MBA 1985 University of Southern California -- Deans List, Albert Quon Community Service Award (for volunteering with the American Longevity Association and helping an elderly lady every other week), George S. May Scholarship, CA State Fellowship. BA psychology, psychobiology emphasis 1983 California State University Fullerton Physiological courses as well as core courses (developmental, abnormal etc). UCLA Psychobiology 1978, one brief but fast moving and fulfilling quarter. Main interest was the electrochemical basis of consciousness. Also seminars at the NeuroPsychiatric Institute. Other: Ongoing conferences, meetings and continuing education. Aging, computer software and information technology. Some molecular biology, biotech, bio and protein informatics, computer aided drug design, clinical medical devices, electronics, HIPAA, fundraising through the Assoc. of Fundraising Professionals. Previous careers include: Marketing Increasing skill set and successes in virtually all phases, with valuable experience in locating people and companies with the greatest need and interest in a product or service, and sitting across the table with decision makers and working out agreements favorable to all. Information Technology: Management, data analysis and programming in commercial and clinical trials systems, and bioinformatics and protein informatics. As IT Director at Newport Beach, CA based technology organization Success Family of Continuing Education Companies, provided online software solutions for insurance and financial professionals in small to Fortune 500 size companies. We were successful with lean team organization (the slower moving competition was unable to create similar software systems). Medical devices: At Omnimedical in Paramount CA developed and managed quality assurance dept. and training depts. for engineers, physicians and technicians. Designed hospital equipment testing program for hospital services division. In my early 20’s I was a musician, and studied psychology and music. Interned with the intention of becoming a music therapist. These experiences helped develop valuable skills used today to advance our shared mission of creating aging solutions.
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