[ExI] [CCM-L] CCM-L Digest, Vol 47, Issue 62
M2darwin at aol.com
M2darwin at aol.com
Fri Jun 14 20:20:10 UTC 2013
I thought my response to this lady, posted on the Gerontology Research
Forum, might be of some interest to CCM-Lers.
In a message dated 6/10/2013 8:43:12 A.M. Pacific Daylight Time,
mallory.e.mclaren at gmail.com writes:
I just came home from a conference about the mechanics of aging in
Baltimore and I went in very hopeful, but left feeling frightened and shocked at
the apparent state of affairs in longevity medicine. The focus was on
"nutraceuticals": cranberries, blueberries, strawberries, cumin, and grapes. As
a layperson, I was thinking "This is horrifying. What on earth are these
scientists thinking, focusing on this stuff??!!?? If we focus on this
stuff we're all going to be in the grave before no time." This is because
nutritional changes are like rearranging deck chairs on a sinking Titanic when
we're talking about preserving life. Even a "layperson" knows that.
I have a hard time marrying my excitement and faith in our future against
the landscape as it exists -- not only in our mastery of biology but in
energy, space and air transport, materials tech, overall infrastructure and
urban planning. I can only continue to do whatever I can on my end of things
(law and governance) to turn red lights green for those who have the
know-how to put rubber to road in making things like gene-changing treatments
come to pass.
Where was I going with any of this? One good strong cup of French press
and reading about Ferraris and gene tech compelled me to start typing. Oh
well! I think my point was that I'm having a hard time juxtaposing what
inspires me: the articles, the TedTalks, the conversations -- versus those
things that cause concern: (oftentimes) the conferences, hearing the actual
scientists talk, what I perceive to be the scientific community's lack of
urgency.
Does anyone out there have any words of reassurance?
-Mallory McLaren
Lady, you crack me up, you really crack me up! I don't know what I find
more amusing, your frantic anger that the pursuit of effective
gerontological research isn't proceeding at the pace you anticipated, or the implied
sense of outrage and entitlement that if things don't change soon, YOU are
going to die! I haven't had such a good hard (crying hard) laugh since the day
before yesterday, when an historian from a major East Coast university
interviewed me for >4 hours about the history of efforts to achieve suspended
animation and radical extension of the human life span from 1968 through
the present.
It seems I'm pretty much a unique specimen in that regard, since almost
all of my "contemporaries" in that effort (from that period) are dead, long
dead, incoherent, or otherwise inactivated by old age. Me, I'm no miracle
Methuselah, I just happened to get involved - deeply involved - in trying to
overcome aging death at the tender age of 13. My contemporaries at that
time were thus probably about the same age as you are now. This was me in
1968:
My Science Fair project was entitled "Suspended Animation in Plants and
Animals," and the following year, an article with this picture of this man
appeared in my local newspaper's weekly Sunday Supplement magazine section in
an article entitled "Will We Live Forever?"
I'm betting you have no idea who this gentlemen was? At the time, he was
one of the foremost and most credible research gerontologists in the world.
His name was Johan Bjorksten, and he had a very clever idea about what
might be the root cause of aging. He had noticed that as organisms age, they
tend to accumulate insoluble, often pigmented matter inside their
non-dividing cells. Lipofuscin, which accumulates most prominently in brain and
cardiac cells, is one such "age pigment." Bjorksten was a chemist, in fact he was
an early polymer chemist, and had invented a number of _refinements_
(http://www.google.com/patents?id=4qxmAAAAEBAJ&printsec=abstract&zoom=4#v=onepage&
q&f=false) to the first practical document duplicating device the
_hectograph_ (http://www.britannica.com/EBchecked/topic/259209/hectograph) , which
had been invented by the Russian Mikhail Alisov, in 1869. Bjorksten
determined that this insoluble material, which could occupy as much as as 30% to
40% of the volume of non-dividing cells in aged animals, consisted largely
of cross linked molecules of lipids and proteins. So molecularly cross
linked, compact and tough was this material that it was completely resistant to
digestion by trypsin and other commonly available "digestive" biological
enzymes.
This posed a puzzle for Bjorksten, because if no living systems could
decompose this material, it was so stable that it would necessarily remain as
indigestible debris after each organism died. Thus, the earth should be
covered in such debris by now! Clearly, this is not case, and so this implied
to Bjorksten that there must, in fact, be living organisms with specialized
enzymes capable of breaking down this material. The source of these cross
links? Free radicals were a good candidate for generating such dense,
insoluble macromolecules.
As it turns out, Bjorksten wasn't far off the mark. Today, we know that
lipofuscin and related species are the indigestible and highly cross linked
debris of old mitochondria that have been reprocessed through the lysosomes
of cells. Bjorksten thought these cross linked molecules interfered with
normal cell metabolism and possibly acted as toxic species which caused cells
to senesce. He set out to find enzymes in nature which could reverse these
cross links and thus, he thought, reverse aging.
Whether or not Bjorksten did indeed find the "microproteases" and
"microlipases" he was looking for remains unknown, but he did find a strain of
microorganism that could digest the age pigment from geriatric humans and
animals in the form of the beta hemolytic bacterium Bacillus cereus - a
ubiquitous bug present in soil which is also the cause of Fried Rice Syndrome - a
variety of "24-hour food poisoning" that is characterized by nausea,
vomiting diarrhea and abdominal cramping. By the early 1970s, Bjorksten was
optimistic he had the tools in hand to if not defeat aging, then to
dramatically prolong lifespan. Of course, Bjorksten has been dead for many years, but
his cross linkage theory of aging lives on. He clearly identified a
significant factor in the pathophysiology of aging - though whether it is a cause
or effect is still a subject of debate.
However, the most important points in this story are: Johan Bjorksten is
dead and you have to do a very careful search of the literature to find out
who he was and what his contributions were to experimental gerontology. He
doesn't even have a Wikipedia page! [A bibliography of Bjorksten's work is
appended at the end.] Bjorksten, and many of his contemporaries in both
experimental and interventive gerontology were truly optimistic that aging
would be conquered in their lifetimes. And who was I, a 15 year old boy, to
disagree?
When Steve Harris says that aging is an incredibly complex problem, he is
right. There's actually a very easy way to tell that he is right, and that
is to look around for any non-aging or immortal mammals, or other
vertebrates, for that matter. There aren't any. Why is that? Well, one cogent
explanation (and probably the correct one) is that for an immortal organism to
exist it would be necessary for it to continuously maintain and repair
itself so that it remained youthful, or at least non-senescent, indefinitely.
Of course, there are a couple of problems with that.
The first is that any such "maintenance program" would necessarily be both
"costly and complex" in evolutionary terms. Think about it, what kinds of
biological, biochemical or other processes would be required to maintain,
say a brain or a heart in indefinite good health? What do you do with cross
linked, let alone mis-folded proteins? What is required to replace one of
those brain cells (and its unique, encoded memory information) if it should
die or be destroyed? We have no idea.
As to evolution in the form of natural selection? Well, the critical
question to ask and answer is, "what incentive would evolution have to "develop"
such complex mechanisms which would also necessarily be energy intensive
(e.g., costly)? The answer would seem to be, "none." In fact, reproduction
seems to be the answer "nature" has arrived at in the face of the ever
increasing costs of maintaining individual organisms in indefinite good health
over long periods of time. The simple fact is that nature simply doesn't do
this. Instead, evolution puts precisely the amount of effort into
maintaining the health and vitality of individual organisms as is justified by the
rate at which they succumb to misadventure and macro- and micro-predation.
The take home message is as brutal as it is simple: somebody is going to
have to create the enormously complex maintenance and renewal procedures for
complex organisms which or nature (or god if you are mystic) had no
"reason" to "write."
I first realized this in my mid-teens - I understood that aging was likely
to be a hugely complex set of problems and that there was unlikely to be
any elixir of youth, or any compound or group of chemical compounds that
would "solve" the aging problem. Aging was going to be a engineering problem
on the molecular, genetic, cellular and even the organismal level, and not a
"pill problem."
So, I asked myself, "Which is the easier problem; achieving suspended
animation or conquering aging, and which is more the stuff of unsubstantiated
science fiction: an anti-aging "immortality pill", or reversible organ
cryopreservation?" As you can see from the news clip above, my bet was on the
latter. That was in 1972 when I was 17 years old. So far, that bet has been
wrong. As it turns out, achieving reversible cryopreservation of a mammalian
kidney or brain is also very, very complicated. See:
http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=2&ved=0CDwQFjAB
&url=http%3A%2F%2Fwww.21cm.com%2Fpdfs%2Fcryopreservation_advances.pdf&ei=3HO
7UdfCIMO-yQHes4GYCw&usg=AFQjCNEpGSqcjH23IQxcWb8BcjtrE_uwKw&sig2=-2b7-Rtatqr0
_xrfztyBWg
Probably still not as complicated as "curing" aging, but still complicated
enough that it hasn't happened yet.
When you write:
"I have a hard time marrying my excitement and faith in our future against
the landscape as it exists -- not only in our mastery of biology but in
energy, space and air transport, materials tech, overall infrastructure and
urban planning."
I don't know whether I want to slap you, or sit down and have a good cry
with you. Since neither of those courses of action seems likely to be
productive, I've chosen, instead, to write this instructional missive.
While I may have been just a kid in 1968, I wasn't a moron and I did not
live in a vacuum. My interests in science and coming developments in
technology was keen. I was an avid reader of classic 1950s-60s science fiction as
well as popular and “hard” science publications and books. In 1968 my
country was the richest and most technologically sophisticated in the world,
and it was about to land a man on the moon, and return him safely to earth.
In fact, it was about to land a number of men on the moon and recover them
all safely. At that time, the United States (US) Federal Government was
funding the National Aeronautics and Space Administration to an unprecedented
degree. Not since the Manhattan Project had so much money and effort been
expended upon a scientific undertaking.
A world view emerged from this effort, and it was a world view
promulgated, endorsed by, and made completely credible to the populace by the US
government. That world view was one that posited as inevitable the construction
of a large, orbiting space station, the establishment of a permanent lunar
base, and the beginning of the expansion of humanity into the solar system –
and more speculatively, beyond.
This worldview is best summarized and most accessible today in the first
half of the film 2001: A Space Odyssey which premiered in 1968, the year I
was becoming deeply involved in cryonics. While the film was undeniably
science fiction in its premise of encountering extraterrestrial life, it‘s
technological predictions of what life would be like at the turn of century
were universally considered completely reasonable by far sighted and
respected scientists and futurists – even conservative ones such Dandridge Cole and
Isaac Asimov.
Below is a picture of my "cryobiology lab" taken in 1973.
If you look closely at the poster on the door you'll see that it is a
promotional poster for the creation of what was to become National Institute on
Aging: "the broad scientific effort to understand the nature of aging and
to extend the healthy, active years of life," The NIA was created in 1974.
I'm still waiting for the first FDA approved "anti-aging pill." Hell, I'm
still waiting for any proven pill that will slow or halt aging, FDA approved
or not.
That world, then over 30 years in the future, became my model, and the
model for millions of other thinking, forward-looking people, young and old
alike, for how the future would be. It was a world where space colonization
was underway, life spans had been modestly extended, human hibernation was
a reality and solid state organ cryopreservation was in use for storing
transplanted organs. It was a reassuring view of the future, and in
particular of my future, if I didn’t die before getting there.
By 1976, like you, I was becoming uncomfortably aware that the future I
expected was not materializing at a rate consistent with the worldview in
2001. Organ cryopreservation programs had been abandoned in all but one
facility in world, the US manned space program was doomed, and interest in
serious, interventive gerontology, let alone meaningful research, was nil.
The money and intellectual resources required to achieve these goals had
been redirected to an endless series of wars, first in Vietnam and later in
the Middle East and East, as well as a succession of botched and
unsuccessful programs to end poverty in the US (the Great Society), cure cancer, and
deal with longstanding mishandling of the environment. The spending spree
of the latter days of the Cold War bankrupted the Soviet Union and, in
truth, bankrupted the West, as well. The focus of the planet‘s population was on
protecting itself against bogeymen of its own making and it spent and
spent maniacally to create weapons systems of vast lethality and ever
increasing complexity.
So, sometime in late in 1976 I wrote out a timeline of milestones that I
thought would be necessary if I were to survive. This was a simple list of
critical achievements with the dates by which they must be accomplished
alongside them. It took a conservative and probably all too unfortunately
realistic prediction, of the likely arc of my productive life which is shown in
the image above.
While it has proved a more accurate road map than my naive first
imaginings of my future, it too has fallen short and has proven flawed, perhaps
fatally flawed. Since I was not then, nor am I now, either poorly informed
about cryonics or lacking in real world experience in its practice, I suggest
you might want to pay careful attention to what went wrong with this very
conservative timeline, because it very likely has important implications for
your future as well.
Whether you believe that it will ever be feasible to "cure frostbite," or
to cure cancer, for that matter, you still can't escape from the question
of which is more likely to save your life; basic research in gerontology, or
basic research in cryobiology that enables truly reversible
cryopreservation of the brain? The latter will provide a kind of one way "medical time
travel." It may be your only chance at an indefinitely long and healthy life.
For myself, I think that a combination of efforts in both cryobiology and
interventive gerontology is likely to be the most productive for healthy,
reasonably young individuals (say, 40 and younger). Fetal stem cells are
now understood to colonize the mother and to be capable of providing
regenerative rescue if non-dividing cells in the maternal heart or brain are
injured during pregnancy. Indeed, fetal-maternal stem colonization occurs even in
the case of surrogacy where there is no genetic relationship between the
fetus and the mother! This suggests that "third party" embryonic stem cells
may be used to achieve critical cellular repair in aged and injured organs
and organisms.
Take a good long look at this paper: Transplantation of mesenchymal stem
cells from young donors delays aging in mice which is available as free
full-text here:
http://www.nature.com/srep/2011/110818/srep00067/full/srep00067.html
The purpose of this research was to treat osteoporosis in old mice. It not
only ameliorated osteoporosis, it markedly extended the life span's of
already aged mice, including the maximum life span of the animals. This
suggests that there may be a way to adapt or hijack existing tissue and organ
repair and regeneration mechanisms that were developed by evolution not to
counter aging, but rather to create new multicellular organisms in the first
place (via embryogenesis/reproduction). See:
Chan WF, Gurnot C, Montine TJ, Sonnen JA, Guthrie KA, Nelson JL. Male
microchimerism in the human female brain. PLoS One. 2012;7(9):e45592. doi:
10.1371/journal.pone.0045592. Epub 2012 Sep 26. PubMed PMID: 23049819; PubMed
Central PMCID: PMC3458919.
Kara RJ, Bolli P, Matsunaga I, Tanweer O, Altman P, Chaudhry HW. A mouse
model for fetal maternal stem cell transfer during ischemic cardiac injury.
Clin Transl Sci. 2012 Aug;5(4):321-8. doi:
10.1111/j.1752-8062.2012.00424.x. Epub 2012 Jun 18. PubMed PMID: 22883609; PubMed Central PMCID:
PMC3419501.
Pritchard S, Bianchi DW. Fetal cell microchimerism in the maternal heart:
baby gives back. Circ Res. 2012 Jan 6;110(1):3-5. doi:
10.1161/CIRCRESAHA.111.260299. PubMed PMID: 22223204.
Lim GB. Stem cells: Do fetal cells repair maternal hearts? Nat Rev
Cardiol. 2011 Dec 6;9(2):67. doi: 10.1038/nrcardio.2011.197. PubMed PMID:
22143081.
Kara RJ, Bolli P, Karakikes I, Matsunaga I, Tripodi J, Tanweer O, Altman
P, Shachter NS, Nakano A, Najfeld V, Chaudhry HW. Fetal cells traffic to
injured maternal myocardium and undergo cardiac differentiation. Circ Res.
2012 Jan 6;110(1):82-93. doi: 10.1161/CIRCRESAHA.111.249037. Epub 2011 Nov 14.
PubMed PMID: 22082491; PubMed Central PMCID: PMC3365532.
There is also rapidly growing understanding about the nature of aging in
the vascular endothelium and with it, emerging possibilities for greatly
slowing it. The uncoupling of nitric oxide synthase (both endothelial and
neuronal) and the accompanying injury from superoxide production, as well as
disrupted signal transduction has been traced to the Rho/Rho-kinase, or ROCK
pathway, and the ROCK inhibitor drug, Fasudil, is already on the market in
Europe. Similarly, the 5-PDE inhibitors, now used to treat erectile
dysfunction and primary pulmonary hypertension have been found to reverse some age
associated changes in the vascular endothelium as well as to induce the
bone marrow to release endothelial stem cells.
When Steve Harris writes that "You lose 100,000 neurons a day, and there's
nothing you can do about it, apparently," he is articulating what has been
our understanding of aging in the brain, until very recently. Recent
research seems to indicate that there is not a great deal of neuronal loss
during aging of the human brain, but rather that there is neuronal cell atrophy
with loss or arborization. See:
Alme MN, Wibrand K, Dagestad G, Bramham CR. Chronic fluoxetine treatment
induces brain region-specific upregulation of genes associated with
BDNF-induced long-term potentiation. Neural Plast. 2007;2007:26496. doi:
10.1155/2007/26496. PubMed PMID: 18301726; PubMed Central PMCID: PMC2248427.
De Foubert G, Carney SL, Robinson CS, Destexhe EJ, Tomlinson R, Hicks CA,
Murray TK, Gaillard JP, Deville C, Xhenseval V, Thomas CE, O'Neill MJ,
Zetterström TS. Fluoxetine-induced change in rat brain expression of
brain-derived neurotrophic factor varies depending on length of treatment.
Neuroscience. 2004;128(3):597-604. PubMed PMID: 15381288.
Khundakar AA, Zetterström TS. Biphasic change in BDNF gene expression
following antidepressant drug treatment explained by differential transcript
regulation. Brain Res. 2006 Aug 23;1106(1):12-20. Epub 2006 Jul 13. PubMed
PMID: 16842762.
Pei Q, Zetterström TS, Sprakes M, Tordera R, Sharp T. Antidepressant drug
treatment induces Arc gene expression in the rat brain. Neuroscience.
2003;121(4):975-82. PubMed PMID: 14580947.
Burke SN, Barnes CA. Neural plasticity in the ageing brain. Nat Rev
Neurosci. 2006 Jan;7(1):30-40. Review. PubMed PMID: 16371948. Fabricius K,
Jacobsen JS, Pakkenberg B. Effect of age on neocortical brain cells in 90+ year
old human females--a cell counting study. Neurobiol Aging. 2013
Jan;34(1):91-9. doi: 10.1016/j.neurobiolaging.2012.06.009. Epub 2012 Aug 9. PubMed
PMID: 22878165.
Freeman SH, Kandel R, Cruz L, Rozkalne A, Newell K, Frosch MP,
Hedley-Whyte ET, Locascio JJ, Lipsitz LA, Hyman BT. Preservation of neuronal number
despite age-related cortical brain atrophy in elderly subjects without
Alzheimer disease. J Neuropathol Exp Neurol. 2008 Dec;67(12):1205-12. doi:
10.1097/NEN.0b013e31818fc72f. PubMed PMID: 19018241; PubMed Central PMCID:
PMC2734185.
Terry RD, DeTeresa R, Hansen LA. Neocortical cell counts in normal human
adult aging. Ann Neurol. 1987 Jun;21(6):530-9. PubMed PMID: 3606042.
In other words, the neurons are still there, but they are disabled and
quiescent. This is similar to what is seen in both bipolar and major
depressive disorder. Importantly, these changes can be reversed in animals using
molecules such as brain derived nerve growth factor (BDNGF). See:
Weissmiller AM, Wu C. Current advances in using neurotrophic factors to
treat neurodegenerative disorders. Transl Neurodegener. 2012 Jul 26;1(1):14.
doi: 10.1186/2047-9158-1-14. PubMed PMID: 23210531; PubMed Central PMCID:
PMC3542569.
Nagahara AH, Bernot T, Moseanko R, Brignolo L, Blesch A, Conner JM,
Ramirez A, Gasmi M, Tuszynski MH. Long-term reversal of cholinergic neuronal
decline in aged non-human primates by lentiviral NGF gene delivery. Exp Neurol.
2009 Jan;215(1):153-9. doi: 10.1016/j.expneurol.2008.10.004. Epub 2008 Oct
25. PubMed PMID: 19013154; PubMed Central PMCID: PMC2632603.
Bishop KM, Hofer EK, Mehta A, Ramirez A, Sun L, Tuszynski M, Bartus
RT.Therapeutic potential of CERE-110 (AAV2-NGF): targeted, stable, and sustained
NGF delivery and trophic activity on rodent basal forebrain cholinergic
neurons. Exp Neurol. 2008 un;211(2):574-84. doi:
10.1016/j.expneurol.2008.03.004. Epub 2008 Mar 19. PubMed PMID: 18439998; PubMed Central PMCID:
PMC2709503.
Capsoni S, Giannotta S, Cattaneo A. Nerve growth factor and galantamine
ameliorate early signs of neurodegeneration in anti-nerve growth factor mice.
Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12432-7. Epub 2002 Aug 30.
PubMed PMID: 12205295; PubMed Central PMCID: PMC129462.
Cooper JD, Salehi A, Delcroix JD, Howe CL, Belichenko PV, Chua-Couzens J,
Kilbridge JF, Carlson EJ, Epstein CJ, Mobley WC. Failed retrograde
transport of NGF in a mouse model of Down's syndrome: reversal of cholinergic
neurodegenerative phenotypes following NGF infusion. Proc Natl Acad Sci U S A.
2001 Aug 28;98(18):10439-44. Epub 2001 Aug 14. PubMed PMID: 11504920; PubMed
Central PMCID: PMC56979.
Conner JM, Darracq MA, Roberts J, Tuszynski MH. Nontropic actions of
neurotrophins: subcortical nerve growth factor gene delivery reverses
age-related degeneration of primate cortical cholinergic innervation. Proc Natl Acad
Sci U S A. 2001 Feb 13;98(4):1941-6. PubMed PMID: 11172055; PubMed Central
PMCID:PMC29361.
Synthetic BDNF mimetics have recently been made which cross the blood
brain barrier and reverse age related changes in the neurons of animals and it
has also been discovered that antidepressants work by acutely increasing
trkB signaling in the brain which in turn results in up-regulated BDNF
production in the cerebral cortex.
Alme MN, Wibrand K, Dagestad G, Bramham CR. Chronic fluoxetine treatment
induces brain region-specific upregulation of genes associated with
BDNF-induced long-term potentiation. Neural Plast. 2007;2007:26496. doi:
10.1155/2007/26496.PubMed PMID: 18301726; PubMed Central PMCID: PMC2248427.
De Foubert G, Carney SL, Robinson CS, Destexhe EJ, Tomlinson R, Hicks CA,
Murray TK, Gaillard JP, Deville C, Xhenseval V, Thomas CE, O'Neill MJ,
Zetterström TS. Fluoxetine-induced change in rat brain expression of
brain-derived neurotrophic factor varies depending on length of treatment.
Neuroscience. 2004;128(3):597-604. PubMed PMID: 15381288.
Khundakar AA, Zetterström TS. Biphasic change in BDNF gene expression
following antidepressant drug treatment explained by differential
transcriptregula tion. Brain Res. 2006 Aug 23;1106(1):12-20. Epub 2006 Jul 13. PubMed
PMID: 16842762.
Pei Q, Zetterström TS, Sprakes M, Tordera R, Sharp T. Antidepressant drug
treatment induces Arc gene expression in the rat brain. Neuroscience.
2003;121(4):975-82. PubMed PMID: 14580947. I've written an extensive summary
here:
http://chronopause.com/index.php/2011/05/30/going-going-gone/
http://chronopause.com/index.php/2011/05/31/going-going-gone%E2%80%A6-part-2
/
http://chronopause.com/index.php/2011/05/31/going-going-gone-part-3/
These are hopeful developments, and they strongly suggest the direction
and nature in which effective, near term interventive gerontological
research should proceed. But they don't by any means constitute any foreseeable
solution to the problems of aging and death. Not for me, and not for you,
either. Any such solution will require the perfection of suspended animation,
as well as huge, complex advances in gerontology.
Most importantly, these developments are not "technological
inevitabilities." In fact, they are technological unlikelihood's unless and until
individuals take action to fight the floodtide of human efforts and desires which
run contrary to these achievements. (See:
http://chronopause.com/index.php/2011/02/07/67/)
The take home message is that even if you do everything you can do to
advance "aging research" you are still going to end up dead - just like Johan
Bjorksten and all the other dead gerontologists.
So, what are you going to do about it?
http://chronopause.com/index.php/2011/04/04/michael-g-darwin-a-biographical-
precis/
Bjorksten Bibliography
1: Bjorksten J, Tenhu H. The crosslinking theory of aging--added evidence.
ExpGerontol. 1990;25(2):91-5. PubMed PMID: 2115005.
2: Bjorksten J. The role of aluminum and age-dependent decline. Environ
Health Perspect. 1989 May;81:241-2. PubMed PMID: 2759061; PubMed Central
PMCID: PMC1567539.
3: Bjorksten JA. Dietary aluminum and Alzheimer's disease. Sci Total
Environ. 1982 Sep;25(1):81-6. PubMed PMID: 7146892.
4: Bjorksten JA. Aluminum as a cause of senile dementia. Compr There. 1982
May;8(5):73-6. PubMed PMID: 7094562.
5: Bjorksten J. Selenium in nutrition. Compr There. 1981 Jul;7(7):35-8.
Review. PubMed PMID: 7026153.
6: Bjorksten J. A unifying concept for degenerative diseases. Compr There.
1978 Jan;4(1):44-52. PubMed PMID: 620512.
7: Bjorksten J. Some therapeutic implications of the crosslinkage theory
of aging. Adv Exp Med Biol. 1977;86B:579-602. Review. PubMed PMID: 333873.
8: Bjorksten J. The crosslinkage theory of aging: clinical implications.
Compr There. 1976 Feb;2(2):65-74. PubMed PMID: 1253543.
9: Bjorksten J, Bloodworth JM Jr, Buetow R. Enzymatic lysis in vitro of
hyalin deposits in human kidney. J Am Geriatr Soc. 1972 Apr;20(4):148-50.
PubMed PMID: 4111563.
10: Bjorksten J, Acharya PV, Ashman S, Wetlaufer DB. Gerogenic fractions
in the tritiated rat. J Am Geriatr Soc. 1971 Jul;19(7):561-74. PubMed PMID:
5106728.
11: Bjorksten J. Approaches and prospects for the control of age-dependent
deterioration. Ann N Y Acad Sci. 1971 Jun 7;184:95-102. PubMed PMID:
5286667.
12: Bjorksten J, Ashman S. Nitrogenous compounds immobilized in an aged
rat. J Am Geriatr Soc. 1970 Feb;18(2):115-23. PubMed PMID: 5461109.
13: Andrews F, Bjorksten J, Trenk FB, Henick AS, Koch RB. The reaction of
an autoxidized lipid with proteins. J Am Oil Chem Soc. 1965
Sep;42(9):779-81. PubMed PMID: 5827901.
14: ANDREWS F, BJORKSTEN J, UND, LAAKSOPERWOOD C, THOMSON D. CHEMICAL
COMPOSITION OF ENZYME-FRACTIONATED AGED HEART TISSUE. J Am Geriatr Soc. 1965
Feb;13:94-102. PubMed PMID: 14255636.
15: Bjorksten J. The crosslinkage theory of aging. J Am Geriatr Soc. 1968
Apr;16(4):408-27. Review. PubMed PMID: 4868749.
16: Bjorksten J. Pathways to the decisive extension of the human specific
lifespan. J m Geriatr Soc. 1977 Sep;25(9):396-9. PubMed PMID: 893909.
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