It may be possible one day to use effective biotechnological therapies in order to achieve extreme lifespans. In the meantime, instead of just waiting for these therapies, it may be more fruitful to live a life of constant stimulation, hyper-connection and avoidance of regularity. This is something that everybody can do today, and may have a direct impact upon radical life extension, not only for the individual but also for society.
For some time now I have been advocating the notion that exposure to meaningful information may be one way of achieving radical life extension. By meaningful information I mean anything that requires action, and not just feeding your brain with routine sets of data. Examples of this include being hyper-connected in a digital world, an enriched environment (both in the personal space and in society as a whole), a hormetic lifestyle, behavioural models such as a goal-seeking behaviour, search for excellence, and a bias for action, as well as the pursuit innovation, diversification, creativity and novelty. Most importantly, the avoidance of routine and mediocrity.
This information-rich lifestyle up-regulates the function of the brain and may have an impact upon cell immortalisation. In my latest paper (http://arxiv.org/abs/1306.2734 I provide an explanation of the exact mechanisms. I argue that the relentless exposure to useful information creates new and persisting demands for energy resources in order for this information to be assimilated by the neurons. If this process continues for some time, there will come a point where our biological mechanisms will undergo a phase transition, in effect creating a new biology. Not one based on sex and reproduction but one based on information and somatic survival.
One possible mechanism involves the immortalisation sequences of germ cells. As we know, the DNA in germ cells is essentially immortal because it is somehow able to repair age-related damage effectively. Recent research shows that some of these immortalisation mechanisms do not originate from the germ cells but from the somatic cells! In other words, our bodily cells create biological material such as error-free sequences of DNA and instead of using this themselves for their own survival, they pass it on to the germ cells to assure the survival of the species. This means that the germ-line remains immortal whereas the bodily cells eventually age and die.
The process may be forcibly changed, by overloading the system with high quality actionable information. As explained above, the assimilation of this information demands so much energy and resources from the organism that there will come a point when nature will have to make a choice: is it more economical from the thermodynamic point of view to continue the current cycle of birth, aging and death (with an immortal DNA), or is it better to downgrade this model and favour a new process of somatic survival and improved development in the same individual who would be able to live much longer? The force of evolution in a modern technological, information-laden niche may eventually favour the latter.
In this essay I argue that technologies and techniques used and developed in the fields of Synthetic Ion Channels and Ion Channel Reconstitution, which have emerged from the fields of supramolecular chemistry and bio-organic chemistry throughout the past 4 decades, can be applied towards the purpose of gradual cellular (and particularly neuronal) replacement to create a new interdisciplinary field that applies such techniques and technologies towards the goal of the indefinite functional restoration of cellular mechanisms and systems, as opposed to their current proposed use of aiding in the elucidation of cellular mechanisms and their underlying principles, and as biosensors.
In earlier essays (see here and here) I identified approaches to the synthesis of non-biological functional equivalents of neuronal components (i.e. ion-channels ion-pumps and membrane sections) and their sectional integration with the existing biological neuron — a sort of “physical” emulation if you will. It has only recently come to my attention that there is an existing field emerging from supramolecular and bio-organic chemistry centered around the design, synthesis, and incorporation/integration of both synthetic/artificial ion channels and artificial bilipid membranes (i.e. lipid bilayer). The potential uses for such channels commonly listed in the literature have nothing to do with life-extension however, and the field is to my knowledge yet to envision the use of replacing our existing neuronal components as they degrade (or before they are able to), rather seeing such uses as aiding in the elucidation of cellular operations and mechanisms and as biosensors. I argue here that the very technologies and techniques that constitute the field (Synthetic Ion-Channels & Ion-Channel/Membrane Reconstitution) can be used towards the purpose of the indefinite-longevity and life-extension through the iterative replacement of cellular constituents (particularly the components comprising our neurons – ion-channels, ion-pumps, sections of bi-lipid membrane, etc.) so as to negate the molecular degradation they would have otherwise eventually undergone.
While I envisioned an electro-mechanical-systems approach in my earlier essays, the field of Synthetic Ion-Channels from the start in the early 70’s applied a molecular approach to the problem of designing molecular systems that produce certain functions according to their chemical composition or structure. Note that this approach corresponds to (or can be categorized under) the passive-physicalist sub-approach of the physicalist-functionalist approach (the broad approach overlying all varieties of physically-embodied, “prosthetic” neuronal functional replication) identified in an earlier essay.
The field of synthetic ion channels is also referred to as ion-channel reconstitution, which designates “the solubilization of the membrane, the isolation of the channel protein from the other membrane constituents and the reintroduction of that protein into some form of artificial membrane system that facilitates the measurement of channel function,” and more broadly denotes “the [general] study of ion channel function and can be used to describe the incorporation of intact membrane vesicles, including the protein of interest, into artificial membrane systems that allow the properties of the channel to be investigated” [1]. The field has been active since the 1970s, with experimental successes in the incorporation of functioning synthetic ion channels into biological bilipid membranes and artificial membranes dissimilar in molecular composition and structure to biological analogues underlying supramolecular interactions, ion selectivity and permeability throughout the 1980’s, 1990’s and 2000’s. The relevant literature suggests that their proposed use has thus far been limited to the elucidation of ion-channel function and operation, the investigation of their functional and biophysical properties, and in lesser degree for the purpose of “in-vitro sensing devices to detect the presence of physiologically-active substances including antiseptics, antibiotics, neurotransmitters, and others” through the “… transduction of bioelectrical and biochemical events into measurable electrical signals” [2].
Thus my proposal of gradually integrating artificial ion-channels and/or artificial membrane sections for the purpse of indefinite longevity (that is, their use in replacing existing biological neurons towards the aim of gradual substrate replacement, or indeed even in the alternative use of constructing artificial neurons to, rather than replace existing biological neurons, become integrated with existing biological neural networks towards the aim of intelligence amplification and augmentation while assuming functional and experiential continuity with our existing biological nervous system) appears to be novel, while the notion of artificial ion-channels and neuronal membrane systems ion general had already been conceived (and successfully created/experimentally-verified, though presumably not integrated in-vivo).
The field of Functionally-Restorative Medicine (and the orphan sub-field of whole-brain-gradual-substrate-replacement, or “physically-embodied” brain-emulation if you like) can take advantage of the decades of experimental progress in this field, incorporating both the technological and methodological infrastructures used in and underlying the field of Ion-Channel Reconstitution and Synthetic/Artificial Ion Channels & Membrane-Systems (and the technologies and methodologies underlying their corresponding experimental-verification and incorporation techniques) for the purpose of indefinite functional restoration via the gradual and iterative replacement of neuronal components (including sections of bilipid membrane, ion channels and ion pumps) by MEMS (micro-electrocal-mechanical-systems) or more likely NEMS (nano-electro-mechanical systems).
The technological and methodological infrastructure underlying this field can be utilized for both the creation of artificial neurons and for the artificial synthesis of normative biological neurons. Much work in the field required artificially synthesizing cellular components (e.g. bilipid membranes) with structural and functional properties as similar to normative biological cells as possible, so that the alternative designs (i.e. dissimilar to the normal structural and functional modalities of biological cells or cellular components) and how they affect and elucidate cellular properties, could be effectively tested. The iterative replacement of either single neurons, or the sectional replacement of neurons with synthesized cellular components (including sections of the bi-lipid membrane, voltage-dependent ion-channels, ligand-dependent ion channels, ion pumps, etc.) is made possible by the large body of work already done in the field. Consequently the technological, methodological and experimental infrastructures developed for the fields of Synthetic
Ion-Channels and Ion-Channel/Artificial-Membrane-Reconstitution can be utilized for the purpose of a.) iterative replacement and cellular upkeep via biological analogues (or not differing significantly in structure or functional & operational modality to their normal biological counterparts) and/or b.) iterative replacement with non-biological analogues of alternate structural and/or functional modalities.
Rather than sensing when a given component degrades and then replacing it with an artificially-synthesized biological or non-biological analogue, it appears to be much more efficient to determine the projected time it takes for a given component to degrade or otherwise lose functionality, and simply automate the iterative replacement in this fashion, without providing in-vivo systems for detecting molecular or structural degradation. This would allow us to achieve both experimental and pragmatic success in such cellular-prosthesis sooner, because it doesn’t rely on the complex technological and methodological infrastructure underlying in-vivo sensing, especially on the scale of single neuron components like ion-channels, and without causing operational or functional distortion to the components being sensed.
A survey of progress in the field [3] lists several broad design motifs. I will first list the deign motifs falling within the scope of the survey, and the examples it provides. Selections from both papers are meant to show the depth and breadth of the field, rather than to elucidate the specific chemical or kinetic operations under the purview of each design-variety.
For a much more comprehensive, interactive bibliography of papers falling within the field of Synthetic Ion-Channels or constituting the historical foundations of the field, see Jon Chui’s online biography here, which charts the developments in this field up until 2011.
First Survey
Unimolecular ion channels:
Examples include a.) synthetic ion channels with oligocrown ionophores, [5] b.) using a-helical peptide scaffolds and rigid push–pull p-octiphenyl scaffolds for the recognition of polarized membranes, [6] and c.) modified varieties of the b-helical scaffold of gramicidin A [7]
Barrel-stave supramolecules:
Examples of this general class falling include avoltage-gated synthetic ion channels formed by macrocyclic bolaamphiphiles and rigidrod p-octiphenyl polyols [8].
Macrocyclic, branched and linear non-peptide bolaamphiphiles as staves:
Examples of this sub-class include synthetic ion channels formed by a.) macrocyclic, branched and linear bolaamphiphiles and dimeric steroids, [9] and by b.) non-peptide macrocycles, acyclic analogs and peptide macrocycles [respectively] containing abiotic amino acids [10].
Dimeric steroid staves:
Examples of this sub-class include channels using polydroxylated norcholentriol dimer [11].
pOligophenyls as staves in rigid rod b barrels:
Examples of this sub-class include “cylindrical self-assembly of rigid-rod b-barrel pores preorganized by the nonplanarity of p-octiphenyl staves in octapeptide-p-octiphenyl monomers” [12].
Synthetic Polymers:
Examples of this sub-class include synthetic ion channels and pores comprised of a.) polyalanine, b.) polyisocyanates, c.) polyacrylates, [13] formed by i.) ionophoric, ii.) ‘smart’ and iii.) cationic polymers [14]; d.) surface-attached poly(vinyl-n-alkylpyridinium) [15]; e.) cationic oligo-polymers [16] and f.) poly(m-phenylene ethylenes) [17].
Helical b-peptides (used as staves in barrel-stave method):
Examples of this class include: a.) cationic b-peptides with antibiotic activity, presumably acting as amphiphilic helices that form micellar pores in anionic bilayer membranes [18].
Monomeric steroids:
Examples of this sub-class falling include synthetic carriers, channels and pores formed by monomeric steroids [19], synthetic cationic steroid antibiotics [that] may act by forming micellar pores in anionic membranes [20], neutral steroids as anion carriers [21] and supramolecular ion channels [22].
Complex minimalist systems:
Examples of this sub-class falling within the scope of this survey include ‘minimalist’ amphiphiles as synthetic ion channels and pores [23], membrane-active ‘smart’ double-chain amphiphiles, expected to form ‘micellar pores’ or self-assemble into ion channels in response to acid or light [24], and double-chain amphiphiles that may form ‘micellar pores’ at the boundary between photopolymerized and host bilayer domains and representative peptide conjugates that may self assemble into supramolecular pores or exhibit antibiotic activity [25].
Non-peptide macrocycles as hoops:
Examples of this sub-class falling within the scope of this survey include synthetic ion channels formed by non-peptide macrocycles acyclic analogs [26] and peptide macrocycles containing abiotic amino acids [27].
Peptide macrocycles as hoops and staves:
Examples of this sub-class include a.) synthetic ion channels formed by self-assembly of macrocyclic peptides into genuine barrel-hoop motifs that mimic the b-helix of gramicidin A with cyclic b-sheets. The macrocycles are designed to bind on top of channels and cationic antibiotics (and several analogs) are proposed to form micellar pores in anionic membranes [28]; b.) synthetic carriers, antibiotics (and analogs) and pores (and analogs) formed by macrocyclic peptides with non-natural subunits. [Certain] macrocycles may act as b-sheets, possibly as staves of b-barrel-like pores [29]; c.) bioengineered pores as sensors. Covalent capturing and fragmentations [have been] observed on the single-molecule level within engineered a-hemolysin pore containing an internal reactive thiol [30].
Summary
Thus even without knowledge of supramolecular or organic chemistry, one can see that a variety of alternate approaches to the creation of synthetic ion channels, and several sub-approaches within each larger ‘design motif’ or broad-approach, not only exist but have been experimentally verified, varietized and refined.
Second Survey
The following selections [31] illustrate the chemical, structural and functional varieties of synthetic ions categorized according to whether they are cation-conducting or anion-conducting, respectively. These examples are used to further emphasize the extent of the field, and the number of alternative approaches to synthetic ion-channel design, implementation, integration and experimental-verification already existent. Permission to use all the following selections and figures were obtained from the author of the source.
There are 6 classical design-motifs for synthetic ion-channels, categorized by structure, that are identified within the paper:
“The first non-peptidic artificial ion channel was reported by Kobuke et al. in 1992” [33].
“The channel contained “an amphiphilic ion pair consisting of oligoether-carboxylates and mono- (or di-) octadecylammoniumcations. The carboxylates formed the channel core and the cations formed the hydrophobic outer wall, which was embedded in the bilipid membrane with a channel length of about 24 to 30 Å. The resultant ion channel, formed from molecular self-assembly, is cation selective and voltage-dependent” [34].
“Later, Kokube et al. synthesized another channel comprising of resorcinol based cyclic tetramer as the building block. The resorcin-[4]-arenemonomer consisted of four long alkyl chains which aggregated to forma dimeric supramolecular structure resembling that of Gramicidin A” [35]. “Gokel et al. had studied [a set of] simple yet fully functional ion channels known as “hydraphiles” [39].
“An example (channel 3) is shown in Figure 1.6, consisting of diaza-18-crown-6 crown ether groups and alkyl chain as side arms and spacers. Channel 3 is capable of transporting protons across the bilayer membrane” [40].
“A covalently bonded macrotetracycle4 (Figure 1.8) had shown to be about three times more active than Gokel’s ‘hydraphile’ channel, and its amide-containing analogue also showed enhanced activity” [44].
“Inorganic derivative using crown ethers have also been synthesized. Hall et. al synthesized an ion channel consisting of a ferrocene and 4 diaza-18-crown-6 linked by 2 dodecyl chains (Figure 1.9). The ion channel was redox-active as oxidation of the ferrocene caused the compound to switch to an inactive form” [45]
B STAVES:
“These are more difficult to synthesize [in comparison to unimolecular varieties] because the channel formation usually involves self-assembly via non-covalent interactions” [47].“A cyclic peptide composed of even number of alternating D- and L-amino acids (Figure 1.10) was suggested to form barrel-hoop structure through backbone-backbone hydrogen bonds by De Santis” [49].
“A tubular nanotube synthesized by Ghadiri et al. consisting of cyclic D and L peptide subunits form a flat, ring-shaped conformation that stack through an extensive anti-parallel β-sheet-like hydrogen bonding interaction (Figure 1.11)” [51].
“Experimental results have shown that the channel can transport sodium and potassium ions. The channel can also be constructed by the use of direct covalent bonding between the sheets so as to increase the thermodynamic and kinetic stability” [52].
“By attaching peptides to the octiphenyl scaffold, a β-barrel can be formed via self-assembly through the formation of β-sheet structures between the peptide chains (Figure 1.13)” [53].
“The same scaffold was used by Matile etal. to mimic the structure of macrolide antibiotic amphotericin B. The channel synthesized was shown to transport cations across the membrane” [54].
“Attaching the electron-poor naphthalenediimide (NDIs) to the same octiphenyl scaffold led to the hoop-stave mismatch during self-assembly that results in a twisted and closed channel conformation (Figure 1.14). Adding the compleentary dialkoxynaphthalene (DAN) donor led to the cooperative interactions between NDI and DAN that favors the formation of barrel-stave ion channel.” [57].
MICELLAR
“These aggregate channels are formed by amphotericin involving both sterols and antibiotics arranged in two half-channel sections within the membrane” [58].
“An active form of the compound is the bolaamphiphiles (two-headed amphiphiles). (Figure 1.15) shows an example that forms an active channel structure through dimerization or trimerization within the bilayer membrane. Electrochemical studies had shown that the monomer is inactive and the active form involves dimer or larger aggregates” [60].
ANION CONDUCTING CHANNELS:
“A highly active, anion selective, monomeric cyclodextrin-based ion channel was designed by Madhavan et al (Figure 1.16). Oligoether chains were attached to the primary face of the β-cyclodextrin head group via amide bonds. The hydrophobic oligoether chains were chosen because they are long enough to span the entire lipid bilayer. The channel was able to select “anions over cations” and “discriminate among halide anions in the order I-> Br-> Cl- (following Hofmeister series)” [61].
“The anion selectivity occurred via the ring of ammonium cations being positioned just beside the cyclodextrin head group, which helped to facilitate anion selectivity. Iodide ions were transported the fastest because the activation barrier to enter the hydrophobic channel core is lower for I- compared to either Br- or Cl-“ [62]. “A more specific artificial anion selective ion channel was the chloride selective ion channel synthesized by Gokel. The building block involved a heptapeptide with Proline incorporated (Figure 1.17)” [63].
Cellular Prosthesis: Inklings of a New Interdisciplinary Approach
The paper cites “nanoreactors for catalysis and chemical or biological sensors” and “interdisciplinary uses as nano –filtration membrane, drug or gene delivery vehicles/transporters as well as channel-based antibiotics that may kill bacterial cells preferentially over mammalian cells” as some of the main applications of synthetic ion-channels [65], other than their normative use in elucidating cellular function and operation.
However, I argue that a whole interdisciplinary field and heretofore-unrecognized new approach or sub-field of Functionally-Restorative Medicine is possible through taking the technologies and techniques involved in in constructing, integrating, and experimentally-verifying either a.) non-biological analogues of ion-channels & ion-pumps (thus trans-membrane membrane proteins in general, also sometimes referred to as transport proteins or integral membrane proteins) and membranes (which include normative bilipid membranes, non-lipid membranes and chemically-augmented bilipid membranes), and b.) the artificial synthesis of biological analogues of ion-channels, ion-pumps and membranes, which are structurally and chemically equivalent to naturally-occurring biological components but which are synthesized artificially – and applying such technologies and techniques toward the purpose the gradual replacement of our existing biological neurons constituting our nervous systems – or at least those neuron-populations that comprise the neo- and prefrontal-cortex, and through iterative procedures of gradual replacement thereby achieving indefinite-longevity. There is still work to be done in determining the comparative advantages and disadvantages of various structural and functional (i.e. design) motifs, and in the logistics of implanting the iterative replacement or reconstitution of ion-channels, ion-pumps and sections of neuronal membrane in-vivo.
The conceptual schemes outlined in Concepts for Functional Replication of Biological Neurons [66], Gradual Neuron Replacement for the Preservation of Subjective-Continuity [67] and Wireless Synapses, Artificial Plasticity, and Neuromodulation [68] would constitute variations on the basic approach underlying this proposed, embryonic interdisciplinary field. Certain approaches within the fields of nanomedicine itself, particularly those approaches that constitute the functional emulation of existing cell-types, such as but not limited to Robert Freitas’s conceptual designs for the functional emulation of the red blood cell (a.k.a. erythrocytes, haematids) [69], i.e. the Resperocyte, itself should be seen as falling under the purview of this new approach, although not all approaches to Nanomedicine (diagnostics, drug-delivery and neuroelectronic interfacing) constitute the physical (i.e. electromechanical, kinetic and/or molecular physically-embodied) and functional emulation of biological cells.
The field of functionally-restorative medicine in general (and of nanomedicine in particular) and the field of supramolecular and organic chemistry converge here, where these technological, methodological, and experimental infrastructures developed in field of Synthetic Ion-Channels and Ion Channel Reconstitution can be employed to develop a new interdisciplinary approach that applies the logic of prosthesis to the cellular and cellular-component (i.e. sub-cellular) scale; same tools, new use. These techniques could be used to iteratively replace the components of our neurons as they degrade, or to replace them with more robust systems that are less susceptible to molecular degradation. Instead of repairing the cellular DNA, RNA and protein transcription and synthesis machinery, we bypass it completely by configuring and integrating the neuronal components (ion-channels, ion-pumps and sections of bilipid membrane) directly.
Thus I suggest that theoreticians of nanomedicine look to the large quantity of literature already developed in the emerging fields of synthetic ion-channels and membrane-reconstitution, towards the objective of adapting and applying existing technologies and methodologies to the new purpose of iterative maintenance, upkeep and/or replacement of cellular (and particularly neuronal) constituents with either non-biological analogues or artificially-synthesized-but-chemically/structurally-equivalent biological analogues.
This new sub-field of Synthetic Biology needs a name to differentiate it from the other approaches to Functionally-Restorative Medicine. I suggest the designation ‘cellular prosthesis’.
References:
[1] Williams (1994)., An introduction to the methods available for ion channel reconstitution. in D.C Ogden Microelectrode techniques, The Plymouth workshop edition, CambridgeCompany of Biologists.
[2] Tomich, J., Montal, M. (1996). U.S Patent No. 5,16,890. Washington, DC: U.S. Patent and Trademark Office.
[69] Freitas Jr., R., (1998). “Exploratory Design in Medical Nanotechnology: A Mechanical Artificial Red Cell”. Artificial Cells, Blood Substitutes, and Immobil. Biotech. (26): 411–430. Access: http://www.ncbi.nlm.nih.gov/pubmed/9663339
*** PLEASE alert your friends—Our own continued health and longevity may depend on Steve continuing his work.***
This call for support was also posted by Ilia Stambler on the Longevity Alliance Website, and organized on YouCaring.com by John M. Adams. Eric Schulke has also helped tremendously in spreading the word about the Fundraiser.
Since founding the Los Angeles Gerontology Research Group in 1990, Dr. L. Stephen Coles M.D., Ph.D., has worked tirelessly to develop new ways to slow and ultimately reverse human aging.
Everyone active in the LA-GRG or the Worldwide GRG Discussion Group have benefited from his expertise. His continual reporting of news about the latest developments to the List and his work in areas such as gathering blood samples for a complete genome analysis of the oldest people in the world (supercentenarians, aged 110+) is ground breaking and far ahead of anything that has ever been accomplished before. Publication of this work is expected in collaboration with Stanford University before the end of the year. Other accomplishments are equally notable
BRIEF summary of his work: L. Stephen Coles, M.D. Ph.D — Cited in more than 250 scientific articles — Profiled as notable person in Wikipedia — Many other contributions to aging research and advancing long, healthy life
Steve Coles was diagnosed with Adenocarcinoma (Pancreatic Cancer) at the head of the pancreas on Christmas Eve of last year. Pancreatic cancer is particularly insidious. He underwent a Whipple (Surgical) Procedure on January 3rd that produced a beneficial result. The tumor’s complete obstruction to the common bile duct that had caused jaundice and severe pruritus (skin itching leading to scratching to the point of bleeding) was almost immediately reversed in two days. His subsequent chemotherapy with Gemzar over the past three months will hopefully prevent metastases from spreading to other organs. But we won’t know his prognosis until June 7th when a CT Scan will be compared with a baseline scan performed before the start of chemo interpreted by a cancer radiologist.
We now have the opportunity to carry out a personalized chemo treatment regimen created by a start-up company called Champions Oncology in Baltimore, MD; USA affiliated with the Johns Hopkins School of Medicine. Champions is a world class organization that will analyze the tissue sample that has already been sent to them. Then, a custom treatment program will be prescribed for Steve based on a mouse model, since each tumor is unique and pure test tube trials have not been shown to be effective.
Champions Oncology’s service is to test in mice what can work for Dr. Coles. This is done through two steps:
(1) To implant Dr. Coles’s cancer on mice. (This part has been successfully carried out, and it will allow us to test nine different treatment protocols on Dr. Coles’s specific tumor tissue in mice).
(2) Test the treatments on the mice (The treatments have been defined with Dr. James P. Watson, Dr. Coles, and his oncologists.)
Dr. Joao Pedro de Magalhes of Liverpool, UK was the first to propose employing the services of Champions Oncology. They have a good track record. The biggest risk is that the process normally takes so long that the patient dies before the results can be obtained (especially with such an aggressive, malignant cancer, as Dr. Coles’s). Luckily, this part went right. Also, there is a risk is that Step-1 won’t work. Luckily for us, this part went right, too. Therefore, so far, it seems that choosing Champions Oncology’s approach was the right choice. We can’t be sure that Step-2 will be as successful, but we need to try.
In addition to his medical team here in the U.S., our international friends have been active on his behalf. They successfully negotiated a 60 percent reduction in cost.
NOW, YOU CAN HELP IN TWO WAYS:
(1) CONTRIBUTE TO THIS FUND
Time is of the essence. The good people at Champions Oncology have agreed to begin the analysis immediately.
Steve Coles needs your support.
It may make THE difference. Please dig deep and support him by contributing to the fund.
*** Our own continued health and longevity may depend on Steve continuing his work.***
(2) SEND REFERRALS TO CHAMPIONS ONCOLOGY
Champions Oncology is an early-stage for-profit company. Champions is not a philanthropy. Like many companies offering breakthrough technologies, it has light bills to pay, payroll to make on time, and many other typical expenses.
Please think of any oncologists how may refer patients to Champions, then contact any of the individuals listed below so we may get life-saving information about Champions into their hands. Champions is particularly well set up to accommodate physicians and patients in the Eastern U.S., Germany, France, Brazil, and Japan.
We wish to acknowledge the GRG (the Gerontology Research Group—A discussion group of ~400 members worldwide.
prayers are on the way for more than 65% of deaths. Aging is a cause of adult cancer, stroke and many others age related diseases. Researchers fighting aging are the best people, they are fighting for all of us. Let’s pay them back!
Bijan Pourat MD
donated$250.00
Saturday, June 01, 2013
Maxim Kholin
donated Hidden Amount
Saturday, June 01, 2013
Aging is a disease. Aging is responsible
Anonymous
donated$60.00
Saturday, June 01, 2013
Nils Alexander Hizukuri
donated$30.00
Saturday, June 01, 2013
All the best!
Anonymous
donated$40.00
Saturday, June 01, 2013
Danny Bobrow
donated Hidden Amount
Saturday, June 01, 2013
Steve, win this fight for us all. I send you healing thoughts.
Danny Steve, friends and family, but it is an outstanding, real-world example of the advancing frontier of science and medicine. The entire life-extension community should rally in support of this effort for Steve and for the acquisition of important scientific knowledge.
In rich countries, more than 80% of the population today will survive past the age of 70. About 150 years ago, only 20% did. In all this while, though, only one person lived beyond the age of 120. This has led experts to believe that there may be a limit to how long humans can live.
Animals display an astounding variety of maximum lifespan ranging from mayflies and gastrotrichs, which live for 2 to 3 days, to giant tortoises and bowhead whales, which can live to 200 years. The record for the longest living animal belongs to the quahog clam, which can live for more than 400 years.
If we look beyond the animal kingdom, among plants the giant sequoia lives past 3000 years, and bristlecone pines reach 5000 years. The record for the longest living plant belongs to the Mediterranean tapeweed, which has been found in a flourishing colony estimated at 100,000 years old.
This jellyfish never dies. Michael W. May
Some animals like the hydra and a species of jellyfish may have found ways to cheat death, but further research is needed to validate this.
The natural laws of physics may dictate that most things must die. But that does not mean we cannot use nature’s templates to extend healthy human lifespan beyond 120 years.
Putting a lid on the can
Gerontologist Leonard Hayflick at the University of California thinks that humans have a definite expiry date. In 1961, he showed that human skin cells grown under laboratory conditions tend to divide approximately 50 times before becoming senescent, which means no longer able to divide. This phenomenon that any cell can multiply only a limited number of times is called the Hayflick limit.
Since then, Hayflick and others have successfully documented the Hayflick limits of cells from animals with varied life spans, including the long-lived Galapagos turtle (200 years) and the relatively short-lived laboratory mouse (3 years). The cells of a Galapagos turtle divide approximately 110 times before senescing, whereas mice cells become senescent within 15 divisions.
The Hayflick limit gained more support when Elizabeth Blackburn and colleagues discovered the ticking clock of the cell in the form of telomeres. Telomeres are repetitive DNA sequence at the end of chromosomes which protects the chromosomes from degrading. With every cell division, it seemed these telomeres get shorter. The result of each shortening was that these cells were more likely to become senescent.
Other scientists used census data and complex modelling methods to come to the same conclusion: that maximum human lifespan may be around 120 years. But no one has yet determined whether we can change the human Hayflick limit to become more like long-lived organisms such as the bowhead whales or the giant tortoise.
What gives more hope is that no one has actually proved that the Hayflick limit actually limits the lifespan of an organism. Correlation is not causation. For instance, despite having a very small Hayflick limit, mouse cells typically divide indefinitely when grown in standard laboratory conditions. They behave as if they have no Hayflick limit at all when grown in the concentration of oxygen that they experience in the living animal (3–5% versus 20%). They make enough telomerase, an enzyme that replaces degraded telomeres with new ones. So it might be that currently the Hayflick “limit” is more a the Hayflick “clock”, giving readout of the age of the cell rather than driving the cell to death.
The trouble with limits
Happy last few days? It doesn’t have to end this way. ptimat
The Hayflick limit may represent an organism’s maximal lifespan, but what is it that actually kills us in the end? To test the Hayflick limit’s ability to predict our mortality we can take cell samples from young and old people and grow them in the lab. If the Hayflick limit is the culprit, a 60-year-old person’s cells should divide far fewer times than a 20-year-old’s cells.
But this experiment fails time after time. The 60-year-old’s skin cells still divide approximately 50 times – just as many as the young person’s cells. But what about the telomeres: aren’t they the inbuilt biological clock? Well, it’s complicated.
When cells are grown in a lab their telomeres do indeed shorten with every cell division and can be used to find the cell’s “expiry date”. Unfortunately, this does not seem to relate to actual health of the cells.
It is true that as we get older our telomeres shorten, but only for certain cells and only during certain time. Most importantly, trusty lab mice have telomeres that are five times longer than ours but their lives are 40 times shorter. That is why the relationship between telomere length and lifespan is unclear.
Apparently using the Hayflick limit and telomere length to judge maximum human lifespan is akin to understanding the demise of the Roman empire by studying the material properties of the Colosseum. Rome did not fall because the Colosseum degraded; quite the opposite in fact, the Colosseum degraded because the Roman Empire fell.
Within the human body, most cells do not simply senesce. They are repaired, cleaned or replaced by stem cells. Your skin degrades as you age because your body cannot carry out its normal functions of repair and regeneration.
To infinity and beyond
If we could maintain our body’s ability to repair and regenerate itself, could we substantially increase our lifespans? This question is, unfortunately, vastly under-researched for us to be able to answer confidently. Most institutes on ageing promote research that delays onset of the diseases of ageing and not research that targets human life extension.
Those that look at extension study how diets like calorie restriction affect human health or the health impacts of molecules like resveratrol derived from red wine. Other research tries to understand the mechanisms underlying the beneficial effects of certain diets and foods with hopes of synthesising drugs that do the same. The tacit understanding in the field of gerontology seems to be that, if we can keep a person healthy longer, we may be able to modestly improve lifespan.
Living long and having good health are not mutually exclusive. On the contrary, you cannot have a long life without good health. Currently most ageing research is concentrated on improving “health”, not lifespan. If we are going to live substantially longer, we need to engineer our way out of the current 120-year-barrier.
Avi Roy does not work for, consult to, own shares in or receive funding from any company or organisation that would benefit from this article, and has no relevant affiliations.
The following article was originally published by Immortal Life
When asked what the biggest bottleneck for Radical or Indefinite Longevity is, most thinkers say funding. Some say the biggest bottleneck is breakthroughs and others say it’s our way of approaching the problem (i.e. that we’re seeking healthy life extension whereas we should be seeking more comprehensive methods of indefinite life-extension), but the majority seem to feel that what is really needed is adequate funding to plug away at developing and experimentally-verifying the various, sometimes mutually-exclusive technologies and methodologies that have already been proposed. I claim that Radical Longevity’s biggest bottleneck is not funding, but advocacy.
This is because the final objective of increased funding for Radical Longevity and Life Extension research can be more effectively and efficiently achieved through public advocacy for Radical Life Extension than it can by direct funding or direct research, per unit of time or effort. Research and development obviously still need to be done, but an increase in researchers needs an increase in funding, and an increase in funding needs an increase in the public perception of RLE’s feasibility and desirability.
There is no definitive timespan that it will take to achieve indefinitely-extended life. How long it takes to achieve Radical Longevity is determined by how hard we work at it and how much effort we put into it. More effort means that it will be achieved sooner. And by and large, an increase in effort can be best achieved by an increase in funding, and an increase in funding can be best achieved by an increase in public advocacy. You will likely accelerate the development of Indefinitely-Extended Life, per unit of time or effort, by advocating the desirability, ethicacy and technical feasibility of longer life than you will by doing direct research, or by working towards the objective of directly contributing funds to RLE projects and research initiatives. Continue reading “Longevity’s Bottleneck May Be Funding, But Funding’s Bottleneck is Advocacy & Activism” | >
I want to live longer and help others do the same. I assumed the most effective way to do that is by understanding the science of aging and then engineering solutions to extend human lifespan. That is why I became a biomedical researcher and over the past several years I have pursued this goal almost single-mindedly.
When a 2004 study showed that reducing the calorie intake in mice extended their life by 42%, I enthusiastically embraced the results and even put myself on a calorie restricted diet. But, subsequently, a 2012 study showed that long-term calorie restriction may not have the promised benefits. On the contrary, fewer calories without the required nutrients might actually cause harm.
Calorie restriction is not the first such “promising” route that eventually did not live up to the promise, and it will not be the last. Antioxidants showed promise in holding back diseases caused by aging, but now we know that antioxidant supplements are more likely to shorten your life.
Earlier in May, researchers showed that reducing a protein called NF-kB in mouse brains modestly improved their lifespan. I am not holding out for this result either. Before too long, I’m sure there will be reports of severe side effects of manipulating levels of NF-kB.
Take it easy
Looking at the data I have come to the conclusion that “doing nothing” may be the best option in most cases. This may not be as pessimistic as it sounds and it is definitely not to say that research in fighting aging must not be carried out.
When I say “do nothing”, I am assuming that you do not smoke or drink too much alcohol, and have access to medical care in case of injury. Such measures are bound to increase your lifespan.
But currently, not intervening in the aging process is more likely to help you live longer than trying any of the methods I’ve mentioned, not by a few months but by many years. Trying any of those interventions may actually cause harm, and will do so for the foreseeable future.
Lesson from the past
The chart below shows the survival rates – the percentage of the population that lives to a certain age – for men in England and Wales from 1860 to 2010.
In the 1860s, more than 20% of children died at birth or soon after. On average, men’s health started to decline around the age of 30, and only about 20% of the population survived for more than 70 years.
By 1910, child mortality decreased, thanks to improvements in hygiene and better medical care. This meant more men lived past the age of 50. Circle A shows this reduction in childhood mortality between 1860 and 2010. But, as can be seen from Circle D, the gain towards the end was not significant. This is because only 30% of males passed the age of 70.
Fifty years later, after the discovery of penicillin and invention of more vaccines, 90% of English and Welsh men lived until 50, and more than half survived to 70. Arrow B marks this trend.
Today almost 80% of men live to the age of 70. Four times as many men reach 70 now than in 1860.
What accounts for the change? Between 1860 and 1960, the significant increase in survival rate was due to medical intervention. Since 1960, the survival curve has improved mainly due to reduction in smoking.
This trend is similar in many rich countries, including the US. Druin Burch, a physician and writer, says in his book Taking the Medicine, that eliminating smoking would provide more benefits than being able to cure people of every possible type of cancer.
Age gracefully
Many experts believe that human lifespan might actually have an upper limit of 125 years. The average may not increase much beyond 90. If we are to agree with them, this leaves little room for improvement.
But we have never concentrated on maximising human lifespan before. Most people believe human lifespan is finite, so all drugs being manufactured today are targeted towards certain age-related diseases such as diabetes and hypertension. They are not designed to extend human lifespan.
If this bleak outlook is indeed true, we should not practise naive interventionism because it is unlikely to help. As Nassim Nicholas Taleb describes in his book Antifragile, naive interventionism occurs when we try to fix a single thing, but end up disturbing a complex system.
In case of extending human lifespan, those naive interventions would include calorie restriction, antioxidant supplements or manipulating the protein NF-kB, as mentioned earlier. They also include the current obsession with replacing fat in foods with sugar, the health benefits of drinking red wine, or the use ofsurgery or supplements to “fight” aging. This latter industry has grown in the past decade from being non-existent to an estimated worth of $88 billion today.
If intervening in the aging process with current biomedical science has any positive effect at all, it will be far too small to worry about. It’s far more likely to harm us.
That is why I have decided to do nothing and follow a simple rule: unless I meet with an accident, or suffer from a terminal disease, I will not add anything to my life with the explicit purpose of extending it. To do anything else would most likely do more harm than good.
Avi Roy does not work for, consult to, own shares in or receive funding from any company or organisation that would benefit from this article, and has no relevant affiliations.
It is often said that empiricism is one of the most useful concepts in epistemology. Empiricism emphasises the role of experience acquired through one’s own senses and perceptions, and is contrary to, say, idealism where concepts are not derived from experience, but based on ideals.
In the case of radical life extension, there is a tendency to an ‘idealistic trance’ where people blindly expect practical biotechnological developments to be available and applied to the public at large within a few years. More importantly, idealists expect these treatments or therapies to actually be effective and to have a direct and measurable effect upon radical life extension. Here, by ‘radical life extension’ I refer not to healthy longevity (a healthy life until the age of 100–120 years) but to an indefinite lifespan where the rate of age-related mortality is trivial.
Let me mention two empirical examples based on experience and facts:
1. When a technological development depends on technology alone, its progress is often dramatic and exponential.
2. When a technological development also depends on biology, its progress is embarrassingly negligible.
Developments based solely on mechanical, digital or electronic concepts are proliferating freely and vigorously. Just 20 years ago, almost nobody had a mobile telephone or knew about the internet. Now we have instant global communication accessible by any member of the general public.
Contrast this with the advancement of biotechnology with regards to, say, the treatment of the common cold. There has not been a significantly effective treatment for the public at large for, I will not say a million, but certainly for several thousand years. The accepted current medical treatment for the common cold is with bed rest, fluids, and antipyretics which is the same as that suggested by Hippocrates. Formal guidelines for the modern treatment of cardiac arrest include chest compressions and mouth- to- mouth resuscitation (essentially the same as the technique used by the prophet Elisha in the Old Testament) as well as intra-cardiac (!) atropine, lignocaine and other drugs used by physicians during the 1930’s. In my medical museum in Cyprus (http://en.wikipedia.org/wiki/Kyriazis_Medical_Museum) I have examples of Medieval treatments for urinary retention (it was via a metal urinary catheter then, whereas now the catheter is plastic), treatment of asthma (with belladonna then, ipratropium now – a direct derivative), and treatment of pain (with opium then, with opium-like derivatives now).
About a hundred years ago, my grandfather (http://en.wikipedia.org/wiki/Neoklis_Kyriazis) wrote a book on hygiene, longevity and healthy life for the public, which included advice such as fresh air, exercise, consumption of fruit and vegetables, avoidance of excessive alcohol or cigarette smoke. These are of course preventative treatments advised by modern anti-ageing practitioners, hardly any progress in a century. In fact, these are the only proven treatments. Even the modern notion of ‘antioxidants’ can be encountered as standard health advice in medical books from the 1800’s. With the trivial exception of a handful of other examples, there has hardly been any progress in healthy longevity at all that can be applied to the common man in the street. Resveratrol? Was a standard health advice in ancient Greek medicine (red wine). Carnosine? Discovered and used 100 years ago. Cycloastragenol? Used in Chinese medicine 1000 years ago.
My question is: how do we expect to influence the process of ageing when we cannot even develop bio-technological cures for simple and common diseases? Are we really serious when we talk about biotechnological treatments that can lead to radical life extension, being developed within the next few years? And if we are really serious, is this belief based on empiricism or idealism? The manipulation of human biology has been particularly tricky, with no significant progress of effective breakthroughs developed during the past several decades. Here I, of course, acknowledge the value of some modern drugs and isolated bio-technological achievements, but my point is that these developments are based on relatively minor refinements of existing therapies, and not on new breakthroughs that can modify the human body in any positive or practical degree. Importantly, even if some isolated examples of effective biotechnology do exist, these are not yet suitable for use by the general public at large.
If we were to compare the progress of general technology with that of life extension biotechnology, we could see that:
A. The progress of technology over the past 100 years has been logarithmic to exponential, whereas that of life extension biotechnology has been virtually static.
B. The progress of technology over the past 20 years has been exponential, whereas that of life extension biotechnology has barely been logarithmic.
It is one thing to talk about future biotechnology developments as a discussion point, and to post these in blogs, for general curiosity. But it is a different thing altogether if we actually want to devise and deliver an effective, practical therapy that truly affords significant life extension.
A different approach is needed, one that does not depend exclusively on biotechnology. It would be naïve to say that I am arguing for the total abandonment of life extension biotechnology, but it is equally naïve to believe that this biotechnology is likely to be effective on its own. A possible way forward could be the attempt to modify human biology not via biotechnology alone, but also by making use of natural, already existing evolutionary mechanisms. One such example could be the use of ‘information-that-requires-action’ in order to force a reallocation of resources from germ-line to somatic cells. This is an approach we currently aiming to describe in detail. My final remark with regards to achieving indefinite lifespan is this: we must engage with technology without depending on biotechnology.
For some general background information on how to engage with technology see:
Freedom fironically found in flesh, not knowing whe’er I’m foul or fowl… tickly bound neath trickly form twisting and more unfresh as dawn upon dawn dies in menstrual skyfire like blood made light — a mocking microcosm of my own transubstantiation from rotting viscera to lightstorm infinity?
Just what sick joke is this? To wake and ache and dream and be and become! – and then to die..? To culminate the very universe itself!.. and then to simply die?! For what I ask you! What! Death… what audacious greed! What reckless squander and heedless extravagance!
Guttural red fringed black a bulbous muck death bastphelgmy! We cannot comprehend the sheer stature of death and so hurriedly cover the unknown with a word to hold it in hand and at a distance, to doubt no doubt.
O pallid heavens! O incessant sun undaunted by my barrenaked finitude! O fetid sanctity wet and redragged as the sickly bloom of jagged flesh! O putrid night sky serene despite my spat fury; as I ebb and ember a’roil withinside my sadness unbelieving and hysteric animal heat that vile sun and auster night jaunt their jeer and mock the rude squall of my panicstrewn death nonetheless.
We must not believe them when they tell us with sad care that we will one day die.
We must not believe them when they tell us that we will escape death by any means but our own daring.
We must bleed our eschaton passion upforth and afroth upon that void hated with awefull grandeur for its monster honesty. We must take self in hand and be/hold the possible futures still fetal inside. We must rage our righteous revolt with pride bright as that unsickened sun, not afraid to boast that we fear death but instead eager to thrust our fervent urgency upon the others still bound to opiate incredulity.
We are Man, and we shall NOT go quietly into that dog night!
Japanese People are Getting Old — Fast. So… Robots! Japan is one of those great examples of how, when a society reaches a certain stage of development, population can stabilize itself based simply on quality of life (economic well-being, healthcare, community, Golden Rule morality, etc.). There is a challenge, however: population decline. In arguably one of the world’s most advanced capitalist nations, where 70% of GDP is based on the services economy and nearly all national debt is public held, a big die-off is… big problematic. Sure, the population decline will be gradual — but it’s inexorable, and Japan has to prepare now.
Make Robots, Not Babies? A (perhaps questionable) study from the Japan Family Planning Association found that 1/3 of Japanese youth have no desire to get their groove on. They just don’t wanna hump each other. And as many of us know, it’s not just an enjoyable hobby, it’s where babies come from! Realistically, a decent number of respondents were probably lying, though. Because in Japan being fake polite and feigning ignorance to the nastiness & porno of human life is… a way of life (that’s a compliment — fake polite is far better than honest rude).
But actually, whether a large segment of the youth truly don’t want to make sweet love, or do, it doesn’t change the fact that Japan’s going to be running out of people. Factor in a rising women’s liberation, the destigmatization of birth control, and perceived economic instability — who knows what the actual equation looks like, but the answer is a birthrate of 1.39. And in case it’s not obvious, a birthrate of at least 2 is a replacement set for the parents; a population at stasis. Ain’t happening.
So, at the end of the day, replacing the lost population with robots, thereby replacing a lost labor force and augmenting the consumer economy — well, seems like a decent enough course of action.
1. Thou shalt first guard the Earth and preserve humanity.
Impact deflection and survival colonies hold the moral high ground above all other calls on public funds.
2. Thou shalt go into space with heavy lift rockets with hydrogen upper stages and not go extinct.
The human race can only go in one of two directions; space or extinction- right now we are an endangered species.
3. Thou shalt use the power of the atom to live on other worlds.
Nuclear energy is to the space age as steam was to the industrial revolution; chemical propulsion is useless for interplanetary travel and there is no solar energy in the outer solar system.
4. Thou shalt use nuclear weapons to travel through space.
Physical matter can barely contain chemical reactions; the only way to effectively harness nuclear energy to propel spaceships is to avoid containment problems completely- with bombs.
5. Thou shalt gather ice on the Moon as a shield and travel outbound.
The Moon has water for the minimum 14 foot thick radiation shield and is a safe place to light off a bomb propulsion system; it is the starting gate.
6. Thou shalt spin thy spaceships and rings and hollow spheres to create gravity and thrive.
Humankind requires Earth gravity and radiation to travel for years through space; anything less is a guarantee of failure.
7. Thou shalt harvest the Sun on the Moon and use the energy to power the Earth and propel spaceships with mighty beams.
8. Thou shalt freeze without damage the old and sick and revive them when a cure is found; only an indefinite lifespan will allow humankind to combine and survive. Only with this reprieve can we sleep and reach the stars.
9. Thou shalt build solar power stations in space hundreds of miles in diameter and with this power manufacture small black holes for starship engines.
10. Thou shalt build artificial intellects and with these beings escape the death of the universe and resurrect all who have died, joining all minds on a new plane.
