Thesis live: 1.1 Turnover or Every cell has a lifespan

In the live thesis building blogxperiment I edit (digest, compile, write, rewrite, delete) my ongoing doctoral thesis in blog posts and put the parts together on thesis live. The title: The physiologic role of stem cells in tissues with different regenerative potential.

1.1 Stem cells and regenerative medicine: basic concepts

/turnover: cellular turnover/

The concept of biological turnover (rate) can be interpreted on many levels: molecules, molecular pathways (signaling), organelles, cells, tissues, organs. The turnover rate by which a biological entity is replaced can be quantified by measuring its half-life. /In abstract form “the half-life of a quantity whose value decreases with time is the interval required for the quantity to decay to half of its initial value” (Wikipedia) I have to check whether it is problematic to explicitly use a Wikipedia entry - I am sure it is used implicitly - in a PhD thesis/ The concept of half-life refers to the time required for an initial quantity of entity E to decay half of its initial value. According to Caplan [reference]: “Every cell in the body has a specific half-life; every cell comes to maturation and will, predictably, drop dead in due course.” For instance erythrocytes have half-lives of 60-90 days and the turnover rate of hepatocytes is 1-2 times/year. On Figure 1 from Caplan the lineage development of a differentiated cell and its replacement cell is delineated. The relative position of these two curves to one another defines growth, steady-state, or atrophy depending on when the first cell dies and when its replacement, the second cell, comes online. /I am not sure here how to solve the problem of legends in the case of figures coming from the literature but I figure it out, here is/

The domesticated biotech future according to Freeman Dyson

Freeman Dyson, old school physics hero conceptualized his rather philosophical thoughts on future biotechnology in a visionary essay in The New York Review of Books, Volume 54, Number 12 · July 19, 2007.

What is surprising to me that according to Dyson “our biotech future” is centered around genetic engineering only, and there is not even a hint to stem cell biology and regenerative medicine, which is a bit strange concept for me concerning state of the art biology.

Anyhow, I ask the readers to form an autonomic opinion about it. Here are some cites: Biology is now bigger than physics, as measured by the size of budgets, by the size of the workforce, or by the output of major discoveries; and biology is likely to remain the biggest part of science through the twenty-first century. Biology is also more important than physics, as measured by its economic consequences, by its ethical implications, or by its effects on human welfare….

I see a bright future for the biotechnology industry when it follows the path of the computer industry, the path that von Neumann failed to foresee, becoming small and domesticated rather than big and centralized. For biotechnology to become domesticated, the next step is to become user-friendly.

Even economists have ideas on the hows of life extension…

Are we really in the age of Regenerative Medicine 2.0? A comparison by Chris Mason

In the age of compelling technology analogies and nomenclatures it was unavoidable that somebody at last identifies enough differences in the history of industrial regenerative medicine to tell Regenerative Medicine 1.0 from 2.0. The man behind is Chris Mason, Group Leader of Stem Cell + Regenerative Medicine Bioprocessing Unit, University College London and cofounder and co-organiser of the London Regenerative Medicine Network (LRMN). His papers can be downloaded from his website and I advise to start with the one titled Regenerative Medicine 2.0, a term also abbreviated as RegenMed 2.0, but I would call it simply RegMed 2.0. The best way to focus on the differences between the 2 periods of RegMed is to show the comparative and quite exhaustive Table 1 made by Chris (in 3 screenshots). It is worth discussing his points and tenets and put the question: Are we really in the age of Regenerative Medicine 2.0 or the analogy with Web 2.0 is unestablished in many respects?

An argument supporting systemic regenerative medicine as a life extension tool

The incentive of this argument is a comment on a post over at fellow life extension blog Fight Aging! titled You Can’t Row the Whole Distance With Oars Made of Stem Cells.

1. Currently the biggest grants in life sciences are in regenerative medicine and stem cell biology.
2. The rate of progress is very fast (if not the fastest) in stem cell biology, tissue engineering, and regenerative medicine comparing to the other branches of life sciences due to the growing number of researchers and grants in the field.
3. Early disruptor candidate stem cell therapies will make regenerative medicine economically and generally acceptable in society.
4. Systemic regenerative medicine is a coherent and inclusive engineering approach to eliminate all aging related problems indefinitely.
Defintion: Systemic regenerative medicine theoretically means the continuous, gradual and consecutive regeneration of every tissue and organ of the human body n times by combined regenerative medicine approaches, i.e. tissue engineering (in vitro grown organs and tissues implants or parts of them), systemic (via circulation) and locally targeted stem and progenitor cell transplantation, and endogenous stem cell niche activation with proper growth factor delivery aiming to maintain the physiological turnover and condition of the human body.

5. Taking the above premises into consideration it is very rational to assume that systemic regenerative medicine has a real chance to reach its goal in itself within the next decades.
/If the current rate of progress will remain stable and will be focused throughout these decades/

The birth of the stem cell niche concept: Schofield, 1978

In David Scadden’s elegant review on The stem-cell niche as an entity of action I found the historically first article in which the concept of the stem cell niche was proposed: “The concept of a niche as a specialized microenvironment housing stem cells was first proposed by Schofield almost 30 years ago in reference to mammalian haematology, although experimental evidence was first provided by invertebrate models”. Now Schoefield is an active researcher since then and the paper was published in Blood Cells. Here is the abstract of the paper, notice the context (primary HSC candidate), the now familiar concepts like “immortality of stem cell population” and also the weird ones like “first generation colony-forming cells”.

“Several experimental findings that are inconsistent with the view that the spleen colony-forming cell (CFU-S) is the primary haemopoietic stem cell are reviewed. Recovery of CFU-S, both quantitatively and qualitatively, can proceed differently depending upon the cytotoxic agent or regime used to bring about the depletion. The virtual immortality of the stem cell population is at variance with evidence that the CFU-S population has an ‘age-structure’ which has been invoked by several workers to explain experimental and clinical observations. To account for these inconsistencies, a hypothesis is proposed in which the stem cell is seen in association with other cells which determine its behaviour. It becomes essentially a fixed tissue cell. Its maturation is prevented and, as a result, its continued proliferation as a stem cell is assured. Its progeny, unless they can occupy a similar stem cell ‘niche’, are first generation colony-forming cells, which proliferate and mature to acquire a high probability of differentiation, i.e., they have an age-structure. Some of the experimental situations reviewed are discussed in relation to the proposed hypothesis.”

Best paper on stem cells and ageing by Thomas Rando: Figure 1

One of the promo material of last December Cambridge Embryonic Stem Cell Symposium was the Nature Insight: Stem Cells which was a supplement in Nature Vol. 441, No. 7097 pp1059-1102 from June , 2006. In it I found the best, brilliantly argumented and conceptualized, data-rich paper of Thomas Rando from Stanford University on Stem cells, ageing and the quest for immortality. I plan to introduce the thoughts of the paper in great details in future posts of Pimm. For today I just copy here Fig. 1: Tissue heterogeneity and stem-cell functionality for homeostasis and repair and the legend because this is the essential starting point of systemic regenerative medicine. Take an hour to think about it.

You can also discuss the paper here, or comment all the reviews of Nature Insight: Stem Cells on a special Nature blog-like surface.

The Scientist on JoVE: Video makes the new science stars?

Thoughtful short piece on the new science video experiment site JoVE in The Scientist blog by Brendan Maher: “Videos like this could cut down troubleshooting time considerably. Moreover, there’s a great opportunity to create some new science stars. Who, after all, doesn’t have a running commentary going through their head as they run through the little tricks that make their experiments work sublimely? Now you can find an audience.” Link

Scientists, scholars in the lab: let us video bioDIY!

Moderate life extension: yes, maximum: no, interview with Huber Warner

Huber R. Warner is a biochemist by profession and he initiated and participated in the development of many research areas including: cellular senescence, oxidative stress, apoptosis, functional genomics, the intervention testing program, and premature aging models. He currently serves on the editorial board of Mechanisms of Ageing and Development, is the editor of the Journal of Gerontology: Biological Sciences, and is a fellow of the Gerontological Society of America. In latest Rejuvenation Research there is a valuable discussion between Warner and de Grey about the SENS project.

1. What is the story of your contra maximum life extension commitment?

I worked at the National Institutes of Health in the USA managing a grant program to fund research on the biology of aging for 21 years (1984-2005). As a member of the Federal government, I learned to be careful when speaking about science and health issues so as not to mislead the public about what had been experimentally proven vs. what was merely promising, hypothetical, or in progress.

2. Do you support moderate life extension? If not, what are your arguments against it?

I’m not against life extension, as numerous experiments with animal models have shown that increased longevity is routinely accompanied by increased health span, something that probably no one is against. However, we felt we had to be careful how we framed our goals, especially when speaking to legislators, as life span extension can conjure up the image of an exploding number of older frail people hanging around draining the resources of the government.

Maximum Life’s James Clement: what can a lawyer do for life extension?

James Clement is an attorney and serial entrepreneur. He is the Chief Operating Officer of Maximum Life Foundation which supports aging and life extension research with a mature and secure VC fund strategy (next blogterviewee, David Kekich, C.E.O. of MaxLife).

1. What is the story of your life extension commitment? I have been interested in life extension ever since I first learned about death as a child. During school, I was always more interested in science than any other subject; but my high-school chemistry teacher was a political activist and encouraged me to study law and change “the System.” Unfortunately, it did not occur to me that I could actually practice life-extension research until I was in law school in the 1980’s, and read Durk Pearson & Sandy Shaw’s “Life Extension Handbook.” I continue to read constantly in diverse scientific fields, especially regarding anti-aging and life-extension, neurophysiology, artificial intelligence, and space. I take about 40 to 50 pills a day, mostly from the Life Extension Foundation, which I believe is the premier vitamin/supplement company in the U.S. I joined the Maximum Life Foundation about a year ago as its Chief Operating Officer, and help its Founder, David Kekich plan and implement strategies for the Foundation to help facilitate anti-aging research.

2. Is it a commitment for moderate or maximum life extension? I am definitely committed to maximum life extension. I appreciate the views of Hans Moravec and others, popularized by Ray Kurzweil in his book “The Singularity Is Near,” that technological change is happening at an exponential rate. While too many people think that super longevity won’t be practical during this century, I believe my generation of Baby Boomers will be the last humans to experience involuntary aging and death from old-age.

3. What is your favourite argument supporting human life extension?Not only will the suffering of disease and aging be alleviated, but human society will be transformed by continuous learning, and a deeper appreciation for the value of life (human and animal) and the environment in which we live.

Life extension interviews: Nick Bostrom and the philosopher’s point of view

Nick Bostrom is an analytic philosopher by profession in Oxford, but he has a strong background in science too. He is also the co-founder and current chair of the World Transhumanist Association.

1. What is the story of your life extension commitment?

I did not think much about the topic until I learned about various possible enabling technologies, and concluded that life extension is feasible. I suppose I was “committed” from that point on.

2. Is it a commitment for moderate or maximum life extension?

For whatever is attainable. Ideally, death should be voluntary. I am assuming we’re talking about extension of health span. I am not committed to indefinite extension of life in a very poor state.

3. What is your favourite argument supporting human life extension?

I’m in favor of research into anti-aging medicine for precisely the same reasons that I’m in favor of cancer research, heart disease research, and diabetes research: because it might prevent or cure disease and save lives.

Commentary on mitochondrial transfer in recent Rejuvenation Research

I published a commentary paper on mitochondrial transfer experiments (PNAS) in recent Rejuvenation Research, impact factor 8.571. Rejuv. Res. is an authoritative peer-reviewed journal and the leading forum publishing solid science to expedite a real cure for aging. Here is the public abstract:

2 more bloggers’ answers: Anne Corwin and Phil Bowermaster

The spectrum of the life extension blogterviewees is broad: scholars, activists, IT people, VC folks, … and is broadening further. Here are 2 more activists/bloggers who put their answers to their blog: Anne Corwin and the aphoristically dense Phil Bowermaster. Thanks for answering. I ‘d like to emphasize that I modified questions 4-5, and introduced a new one:

Blogterview with Aubrey de Grey: life extension stories

Aubrey de Grey is the man, who first made serious, scientifically conceptualized life extension speech acceptable within scholarly circles through good timing, well-done strategy and with a little bit of luck. The rest is … (I’ve slightly modified the original question 4 and separated questions concerning the probable technologies of moderate and maximum life extension.)

1. What is the story of your life extension commitment?

I can’t trace when I realised that aging was a bad thing — I must have been so young that I can’t remember. But I was nearly 30 before I found out that most other people don’t think the same, or at least don’t think that it’s important enough to work on. I was in a very lucky situation to be able to make a contribution - I had training in research in a very different field, and I also had quite broad knowledge of biology - so I decide to have a go. My first publication was very well-received, so I kept going!

2. Is it a commitment for moderate or maximum life extension?

Maximum (i.e., indefinite). Aging doesn’t just kill people, it causes a huge amount of suffering in the process. Aging at a later age would also cause suffering, so it’s just as bad. It amazes me that people deny this.

3. What is your favourite argument supporting human life extension?

Well, there are so many that it’s hard to choose! - but I think the one that’s strongest of all is the alleviation of suffering. However, any argument based on the alleviation of suffering cannot stand on its own, because we evidently value the lives of people who are permanently sick as well as people who are healthy.