Re: [GRG] Editorial Part 2: Strong vs. Weak Force of Aging

Paul and Allen: I agree with your criticism, but everyone
must understand that my purpose
in this 2-part Editorial was to awaken the masses to the complexity of
biology in  determining
the phenotype of longevity.  Nature is not your friend, nor were our
ancestors born in the
Garden of Eden.  We delude ourselves if we think that an answer to
aging lurks around the
corner, just because we wish it were so.  Otherwise, you are
preaching to the choir.– Steve Coles
PS. The correct mathematical term is “spline” function below,
not “spleen” function as my Eudora
spell-checker wished it were so. — Steve Coles
At 11:43 AM 9/4/2014, you wrote:
Cogent points, Paul. I concur.
— Allen Taylor
**Paul Wakfer in reply to Steve Coles …
Steve,
Although I fully understand what you are trying to say and I even agree
with it, nevertheless I think that text such as:
“If the Calment Limit (122 yo) is valid for humans as a maximum
lifespan dictated by our genomes in our lifetimes, it makes no sense to
scrupulously follow the perfect
exercise program; you’re still going to die. It makes no sense to follow
the perfect nutrition program; you’re still going to die.  It makes
no sense to implement the perfect supplement program;you’re still going
to die.”
creates an artificial conflict between the twin actions of:
1) Do everything possible with current scientific information to live as
long as possible in excellent health and vitality, both physically and
mentally; and
2) Do the fundamental research to understand aging sufficiently to
eliminate decline of function with age (as a necessary part of the human
development program).
Particularly, your repeated use of “it makes no sense”
completely negates the value of all the work that I and many others are
doing to organize and present all the current healthspan and longevity
extending therapies as a practical approach for non-scientist life
extensionists.
I assume that you are addressing your piece to the research community to
exhort them to stop wasting their time on remedial bandaid methods and
instead aim at a more fundamental level, but I would maintain that you
most certainly do not at the same time want to dissuade them or anyone
else from using all currently known health and longevity extending
therapies or else those researchers will themselves not live long enough
to make maximal possible contributions toward the goal you are
promoting.
With the text: “it could well be futile to intervene at the level of
telomere relengthening, mitochondrial dysfunction, or antioxidants to
overcome Reactive Oxygen Species”, your piece is also attempting to
create a conflict with a third interim action of which SENS is probably
the best example. So together these 3 actions are actually:
1) Do everything possible with current scientific information to live as
long as possible in excellent health and vitality, both physically and
mentally,
2) Development methods to fix all the dysfunctions of human aging age as
and when they occur; and
3) Do the fundamental research to understand aging sufficiently to
eliminate decline of function with age (as a necessary part of the human
development program).
Personally I (and I think this goes for most life extensionists) see no
conflict whatever between all three of these. Most certainly my
Live120Plus project to fully research and organize the first of those 3
will be supporting and adopting any of the results of 2), and also the
approach of 3) (both with funding as and when the project becomes
profitable).
But please change your approach to not be so negative and denigrating to
the actual pursuit of both 1) and 2), at least as interim measures to
remain alive individually, because it is impossible to know how long 3)
will take to bear fruit or even if it is actually possible.
–Paul
On 14-09-04 02:00 AM, L. Stephen Coles M.D. Ph.D. wrote:

To Members and Friends of the Los Angeles Gerontology Research
Group:
“Compared with Growth and Development, Aging (Entropy) Is a
Comparatively Weak Force”
        If we are to
successfully  intervene in the aging process, it clearly makes more
sense to intervene
in the strong force (development) than in the weak force
(entropy).  Therefore, it could well be futile
to intervene at the level of telomere relengthening, mitochondrial
dysfunction, or antioxidants to overcome
Reactive Oxygen Species (ROS).  If the Calment Limit (122 yo) is
valid for humans as a maximum
lifespan dictated by our genomes in our lifetimes, it makes no sense
to scrupulously follow the perfect
exercise program; you’re still going to die. It makes no sense to
follow the perfect nutrition program;
you’re still going to die.  It makes no sense to implement the
perfect supplement program;you’re still
going to die.  If you adopt a caloric restriction program,
you’re still going to die.  It’s not that these
programs would be counterproductive (life shortening). To the
contrary, they would buy you more time
on the way to the Kurzweil Singularity by increasing your average
life expectancy.  But you’re still going
to die.  On the other hand, if we are to intervene in our
developmental program while still preserving the
architecture of our adult bodies, we need to be able to recapitulate
the genes of “youthfulness” in the
context of middle/old age. 
        First, we have to properly
frame the problem of developmental interventions by decomposing
the program  into a series of subroutines. each operating at a
different order of linear magnitude. At the
top (systemic) level (one to two meters) the only advice is, if
something goes wrong (extrinsic aging),
consult your personal doctors(s), so you don’t die prematurely for
lack of conventional medical care.
Also, follow good lifestyle habits to avoid failure to achieve your
maximum potential lifespan by prematurely
terminating your developmental program through smoking or
obesity.    At the next level down, we must
examine your developmental clock.  This is located in the brain
in  region called the Suprachiasmatic
Nucleus (SCN), which counts the days one by one (circadian rhythm).
The mechanism for this counting
process in conjunction with he pineal gland that synchronizes
light/dark cycles (24 hours) is not well
understood, but it is thought to involve some unique neural peptides
that synchronize organ level clocks
that go haywire whenever you move across multiple time zones, such as
flying from Los Angles to Paris
in one day.
        At the next level down, we
must understand the phenotypic development software through the
Neuro/
Endocrine/Immune Axis (NEIA). But how the hypothalamus communicates
with the pituitary gland along
with the thyroid, the adrenal cortex, the gonads, and the thymus
through a variety of hormonal feedback
loops is not well understood.  Resynchronizing the SCN in model
organisms may adjust all feedback loops
in one fell swoop (or not). 
        The next level down is at
the tissue/cellular level throughout the body.  (There are over 200
histologically
distinct cell types in the mature human adult containing a total of
[50 – 70] trillion cells ).  Here we must ask
what are the consequences of hematogenously infusing millions of
clonal, autologous (histocompatible),
pristine (mutation free), Embryonic Stem Cells (ESC’s) into an adult
body (first in mice and rats and then
in monkeys) over a monthly treatment interval for a time course of
five years?  This would create heterochronic
tissues (mixed old and young) for which there may be an inherent
incompatibility in the intracellular matrix,
as this is not a standard practice conducted by Nature’s
software.  If our goal is to recapitulate youthfulness
in old tissues, we may have to assess the density of senescent cells
that simply stop making a functional
contribution to their respective tissues/organs while continuing to
consume oxygen and nutrients.  Apoptosis
of these tired cells is not normally a housekeeping task performed by
Nature unless the cells were premarked
for obliteration because they were part of a construction scaffold
during fetogenesis, like the webbing between
the fingers and toes.  (Polydactylly [six fingers and toes on
each limb] can be inherited.)   
        If this intervention were
to work, one would not need to intervene at lower levels, such as
organelles like
mitochondria.  Although this cellular engineering program may
take several more years if we were start tomorrow,
it is deeply frustrating to me that we haven’t started already. 
Scientists whose heart is in the right place remind me
of the proverbial drunk looking for his lost keys in a dark parking
lot under the lamp post, since that’s where
the light is.  Doctors have a non-convergent strategy of
attempting to cure one chronic age-related disease at a
time.  Yet,  it is the aging  process itself that is
the root cause of all the degenerative diseases  so well
described
in pathology textbooks.  To decompose the process into three
separate spleen functions in the life history of a
typical mammalian creature…
     LIFE HISTORY of a Mammal (Fitness vs.
Chronological Time)
          
|           
12222222222222222222222222222222222222222222222223
          
|   
1                                                                                                           
3
fitness  | 
1                                                                                                                
3
        
1|                                                                                                                      
3
        1
|                                                                                                                        
3
     x
__

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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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