Re: [GRG] Longevity lessons from Brandt’s bat, the little brown bat, and the naked mole-rat

 James and Johnny,


Kudos to James for this tour de force survey, but I think a few points may be less certain than portrayed.


For example, much emphasis is placed on IGF-1 signaling in Brandt’s bat, and how that makes the bat small, but the fact that it is small is not unique:  it is unique because it lives longer than other species that are equally small. It may be that IGF-1 signaling is low in this particular bat, but it may be equally low in the species that have a longevity quotient less than 1 and are as small as, or smaller
than, Brandt’s bat:  do we really know?  Have the GH/IGF-1 receptors and signalling really been worked out in sufficient molecular and physiological detail in all of the species with hum-drum lifespans to verify that the bat is actually different in this respect?  Is it not possible that, in fact, IGF-1 signaling might be one of the LEAST unique features of this particular species?  And how does IGF-1 signalling in Brandt’s bats compare with other species that may not have the same LQ as this bat, but come close to it?  Do we know?  Might it be that the secret, if there is one, regarding IGF-1 is not IGF-1 signaling per se but uncoupling between IGF-1 signalling and Foxo repression in this species?  And it
is common to lump insulin signaling and IGF-1 signaling into the same category, perhaps because it is hard or impossible to distinguish between these pathways in C. elegans, but these signaling pathways are distinct and have different effects, and I would like to see more of a distinction made between the two. 


Another consideration for drawing conclusions about human implications is that human interventions are likely to be carried out on adults, whereas what we know about the role of IGF-1 signaling in aging seems confined to situations in which IGF-1 signaling is modified during early development and not selectively in the adult, and these are completely different biological states.  We are not going to drop IGF-1 levels in children, but evidence in favor of dropping IGF-1 levels in adults is weak at best.  Adult rodents given even large doses of growth hormone do not have shortened lifespans depite presumably greatly increased IGF-1 signalling.  It is well known that events in early life and adolescence program the way aging unfolds in the adult, but that does not mean that modifications applied in youth will have the same effects if applied only in adults.  Adult humans with higher IGF-1
levels are healthier than adults with lower IGF-1 levels, are less frail, are less represented in hospitals and nursing homes, and, if memory serves, may even live longer, as long as levels are not excessive.  Humans with defective GH/IGF-1 signaling and associated longevity (a very weak effect, it seems, though) were undoubtedly affected by those defects in early youth, and not solely as adults.  IGF-1 expression in the brian is also required for preserving cognition into older age, without which aging interventions will be to little avail.  And as we age, it is insulin
levels that rise, while IGF-1 levels actually fall.  So at least in that sense, higher IGF-1 levels are not associated with increased aging in humans, but higher insulin levels are notoriously associated, linked to diabetes and all that comes with it, whereas the hallmark of the CR effect is lowered insulin levels.  It is too easy for these distinctions to be overlooked in trying to extrapolate from other species to humans, but if we are serious about looking at possible interventions, we have to remember them.


Another major point is the extreme degree of fasting/hibernation/estivation claimed for this species.  That strikes me as far more likely to be unique enough to account for the observed LQ score.  Crudely speaking, if these animals take a holiday from aging 75% of the time (depriving aging mechanisms of the energy needed to drive them, perhaps in analogy to
the daur state in C. elegans?), then this might be imagined to account for a four-fold increase in LQ all by itself.  If so, then drawing conclusions about Brandt’s bat LQ based in large part on IGF-1 signaling loses a lot of its force.


I won’t continue on with the wonderful naked mole rat, but they seem
not to age at all until shortly before they die, and I doubt that this is mostly due to unusual IGF-1 signaling.  It’s not even due to their immunity to cancer.  Something else is at work, and I would sure like to know more about how their Foxo expression looks, and how they compare to C. elegans that live 10 times longer than wild type in terms of their pattern of gene expression.   But
I digress! 


I hope to be forgiven, at least provisionally, for not documenting my facts above, but doing so would have taken so much time as to make it impossible for me to comment at all in a timely fashion, and I hope what I’ve said is largely common knowledge anyway, and that much of what
I’ve said is just a reminder for many of you.  If not, I will dig up references for anyone who needs them, no problem.



On Thursday, January 29, 2015 4:40 PM, “John M. “Johnny” Adams, GRG Exec Director” wrote:


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. 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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