Life extension people are happy: keep living, please!

I found this picture of Aubrey de Grey with his book Ending Aging on his head at the BIL conference in Quinn Norton’s Flickr Stream. Quinn Norton is a bodyhacker technophiliac journalist photographer. Robust, healthy lifespan extension can easily be interpreted as an extreme body-, life- and biohack so no wonder that more and more geeks are turning their attention to this little, unsolved hack. Maybe with time they will learn not just how to write the names properly but how to set up a private lab and isolate DNA and stem cells, at home. (blogging pictures = not enough time to write posts)

Biotech DIY for aging/life extension research: the double future?

“The best way to predict the future is to invent it.” - said Alan Kay, computer legend in 1971.

Recently I had a comment dialogue with Chris on whether state-supported research or industrial business enterprises can (or should) lead to big progress in robust and healthy life extension technologies. Besides the government and corporation coin the research breakthrough could come from an aging focused foundation like the non-profit Methuselah Foundation behind the SENS approach, which supports research projects (like MitoSENS and LysoSENS) and scientists (like Mark and John) through cooperation with university labs. And finally, there is going to be another option to contribute:

Imagine the following future scenario: biotech DIY is becoming an accepted home activity so geeks are setting up private labs and conduct basic in vitro (but not in vivo) research.

Very well informed Stanley Bing on life extension

Huffington Post, Fortune’s Stanley Bing: The Next Big Thing? Please pay extra attention to the language here (especially transmogrification).

Human genome schmutz: Nobody wants to get old or worse, appear old. And forget about dying. That’s the ultimate bummer. Genetic research has been held back recently by a series of disasters too terrible to mention in this venue, or even look up right now, since we’re very busy. But the three-headed midget sheep problem will be solved by 2014 and recombinant DNA, stem-cell and mitochondrial transmogrification technology will begin making inroads into the problem of aging, extending human life to its ultimate limit and even beyond, particularly for really rich people who are on everybody’s nerves already. Another enormous opportunity for confabulators here.

Well, why exactly am I working with human mitochondria and stem cells at the bench? Maybe it’s time again to recall.

Understanding Aging Conference in L.A.: de Grey, Conboy, Wagers and many others…

Looks like the scientist coalition behind healthy life extension is widening. In line with that the question Why was life extension ruled out of the 14 Grand Engineering Challenges? is fading away.

Here is an Aubrey de Grey message from my mailbox:

All details, including forms for abstract submission and
online registration, are at the conference website:

http://www.mfoundation.org/UABBA/

The preliminary program already has over two dozen confirmed
speakers, all of them world leaders in their field. As for previous
conferences I have [co-]organised, the emphasis of this meeting is on
“applied biogerontology” — the design and implementation of
biomedical interventions that may, jointly, constitute a
comprehensive panel of rejuvenation therapies, sufficient to restore
middle-aged or older laboratory animals (and, in due course, humans)
to a youthful degree of physiological robustness. The list of
scientific sessions and confirmed speakers is as follows:

DNA damage, telomeres, cancer
Adam Arkin, Lawrence Berkeley National Laboratory; Jan Vijg, Buck
Institute for Age Research; Jerry Shay, U. Texas Southwestern;
Claudia Gravekamp, Pacific Medical Center Research Institute; Zheng
Cui, Wake Forest University School of Medicine; Rita Effros, UCLA

The cell niche
Irina Conboy, U. California Berkeley; Judith Campisi, Lawrence
Berkeley National Laboratory and Buck Institute; Leanne Jones, Salk
Institute; Ken Muneoka, Tulane University; Kevin Healy, Stanford
University

induced Pluripotent Stem cells from a 69 year old human: the hidden story?

The successful reprogramming (dedifferentiation) of differentiated human somatic cells into a pluripotent, embryonic stem cell-like state called induced pluripotent stem cells (iPS) using just 4 (and recently 3) introduced transcription factors is the biggest news of current stem cell biology. In the paper published in Cell by the Yamanaka group (Takahashi et al.) the iPS clones derived from the facial dermis of a 36-year-old Caucasian female were highlighted. Out of 50 000 retrovirally transduced fibroblasts 10 hES cell-like colonies were observed. But what I found really thought provoking (and poorly discussed in the blogosphere) is that with the same approach iPS cells were generated from the synovial tissue of a 69-year-old Caucasian male. Interestingly out of 50 000 modified cells 17 hES cell-like colonies were found. This finding could easily be relevant from a stem cell aging point of view.

During ageing there is an overall decline in tissue regenerative potential, but it is not clear whether it is due to the intrinsic exhaustion of the adult tissue stem cells or the diminished functionality of the stem cell niche or a change in the systemic milieu. Answers could be different - tissue by tissue.

But if a terminally differentiated connective tissue cell, like the synoviocyte above could be completely reprogrammed from a 69 year old, otherwise health individual into a pluripotent state….well it could it be interpreted as an argument against the cell-intrinsic genetic aging program in adult and aged connective tissues with some cautions.

Caution 1: What if the source of the iPS cells were not really terminally differentiated, but undifferentiated stem or progenitor cells coexisting in fibroblast culture. This problem has been discussed in the paper and forms the Achilles’ heel of it.

Caution 2: The reprogrammed iPS cells from an aged person are behaving the same way as the iPS cells from a younger person with no additional cellular aging characteristics.

As the critical tail of almost every peer-reviewed paper used to say: Further study is needed.

Here is the paragraph on the synoviocytes and the tables and figures are in the supplemental data.

Stat freaks, are you ready to play with the SCImago Journal & Country Rank?

Finally the Google PageRank algorithm, the core analysis tool of the current web is back to where its idea is originated from, scientific citation analysis. The recently launched SCImago Journal & Country Rank database uses an algorithm very similar to PageRank. It has a new metric: the SCImago Journal Rank (SJR). According to Nature:

A new Internet database lets users generate on-the-fly citation statistics of published research papers for free. The tool also calculates papers’ impact factors using a new algorithm similar to PageRank, the algorithm Google uses to rank web pages. The open-access database is collaborating with Elsevier, the giant Amsterdam-based science publisher, and its underlying data come from Scopus, a subscription abstracts database created by Elsevier.

The SJR also analyses the citation links between journals in a series of iterative cycles, in the same way as the Google PageRank algorithm. This means not all citations are considered equal; those coming from journals with higher SJRs are given more weight. The main difference between SJR and Google’s PageRank is that SJR uses a citation window of three years.

From now on every stat geek can compare journals to journals, countries to countries based on different metrics like citable documents, cites, self-cites or the new h-index and get a ticket to recursive heaven. Of course I started with the comparison of Nature and Science to find something very different. I couldn’t. I predict that self-cites will show a lot on how things are going on at different scientific journals and the stats will be used as serious arguments in many blog posts. But here let me share some graphs on the quick comparison of USA, UK and China in the category of Aging.

First graph: citable documents

Science’s Netwatch: Aging blog in focus

Here is another sign that the editors at Science Magazine are taking more and more attention to the web and the scientific blogosphere: Ouroboros (that is: Chris, Okie and Lev) was picked up in the Random Samples column of the current Science issue: “But research on aging is booming, and the field’s good health is on display at the blog Ouroboros, which is named for a symbol of endlessness. Three postdocs from leading aging research labs offer their takes on the latest results from conferences and the literature. The site is aimed at researchers, but it can also help beginners get up to speed.”
It seems that the editors are sharing my opinion that Ouroboros is one of the best science blogs out here and it is also worth mentioning that Chris Patil’s incentive of Ouroboros was Science Magazine’s SAGE KE.
Another remarkable thing is Chris’s approach of developing a group blog instead of building an individual brand and focusing exclusively on biogerontological peer review literature and conferences.

Unpublished SENS3 conference report for mainstream scientists!

Recently I wrote a meeting report on the SENS3 conference for a very prestigious science journal, but finally it did not go through the filters. I knew that the chance for publication is small as the journal rarely publish such meeting reports and as it was in many respects an unconventional science conference. The standards were really high and the genre itself is strictly restricted: no more than 900 words and only 1-2 conference topic could be covered focusing on new data. On the whole it was a really good science writing experience for me. I finally realized how challenging it is to introduce the concept of robust scientific life extension for the mainstream science audience although it is not impossible at all.

But if a man has an interactive blog with a quality readership even an officially unpublished text could be useful, so please read my draft in its final form and think about it. Links of the video versions of the referred presentations and references are included, a perpetual advantage of the web comparing to offline publication. I’d like to say thanks for the folks who helped me with the draft: Aubrey de Grey, Michael Rae, Mark Hamalainen from within the SENS camp, Matthew Oki O’ Connor and Chris Patil, fellow scientists-bloggers and first of all, Anna.

Subject scrapline: Biotechnology

Title: Translating ageing

Summary: A recent unconventional strategic conference on translational science in ageing related damages helps to put some puzzle pieces together.

Changes in the adult tissue stem cells or in the mitochondria are two main processes under constant investigation amongst researchers curious about the ins and outs of the ageing process. At the SENS3 conference in Cambridge scientists and laymen shared their results and ideas, respectively.＊

Despite its mixed population with a scientist majority, the conference resembled a mainstream life science conference due to its topic sessions focusing on the different types of lifelong, ageing accumulated damages. SENS decodes as Strategies for Engineered Negligible Senescence, which aims to suggest a panel of interventions on how to robustly extend the mean and maximum human life span and claims to identify the adequately exhaustive list of main age-related pathologies ranging from cell depletion to mitochondrial mutations. SENS is by definition a flexible enough umbrella term to include other coming life extension technologies and concepts under its brand. Also, it is an engineering project compiled by main organizer Aubrey de Grey, a computer scientist turned theoretical biologist with a grand mission and hypotheses yet to be experimentally tested. The presentations were mainly reviewing the progress in the related branches, with enough new data to keep the experts interested.

Stem cells exhausted

The Open Aging Journal wants you to submit articles!

My gmailbox says and I see no reason not to share it: The Open Aging Journal is an Open Access online journal, which publishes research articles, reviews and letters in all areas of aging science.

The journal aims to provide the most complete and reliable source of information on current developments in the field. The emphasis will be on publishing quality articles rapidly and making them freely available to researchers worldwide. All articles are deposited in at least one major international open digital repository (such as PubMed Central). All articles are indexed by Google and Google Scholar which offers additional massive world wide web exposure.

Biomarkers of aging conference in New York City

In order to slow the progress of aging and prevent age-related disease (which is not the same as figuring out a robust engineering plan for unlimited healthy life extension) biological measures (biomarkers) of aging or disease mechanisms are needed that anticipate clinical disease and are sensitive to functional organism aging.

The American Federation for Aging Research is the organizer of a one-day conference on October 2 in Manhattan focusing on current and future status of biomarkers as identifiers of rates of biological aging, predictors of longevity and predictors of susceptibility to disease.

/Thanks for the tip, Jim Craig./

“Mitochondrial Oasis Effect”: fasting => NAD+ up in mitos => cell survival

Quick storytelling through citations (alert from Jim Hardy, thanks):

Cell: Nutrient-Sensitive Mitochondrial NAD⁺ Levels Dictate Cell Survival

A major cause of cell death caused by genotoxic stress is thought to be due to the depletion of NAD⁺ from the nucleus and the cytoplasm. Here we show that NAD⁺ levels in mitochondria remain at physiological levels following genotoxic stress and can maintain cell viability even when nuclear and cytoplasmic pools of NAD⁺ are depleted. Rodents fasted for 48 hr show increased levels of the NAD⁺ biosynthetic enzyme Nampt and a concomitant increase in mitochondrial NAD⁺. Increased Nampt provides protection against cell death and requires an intact mitochondrial NAD⁺ salvage pathway as well as the mitochondrial NAD⁺-dependent deacetylases SIRT3 and SIRT4. We discuss the relevance of these findings to understanding how nutrition modulates physiology and to the evolution of apoptosis.

Scientific American: Eat (Less) to Live (Longer)

Researchers report in the journal Cell that the phenom is likely linked to two enzymes—SIRT3 and SIRT4—in mitochondria (the cell’s powerhouse that, among other tasks, converts nutrients to energy). They found that a cascade of reactions triggered by lower caloric intake raises the levels of these enzymes, leading to an increase in the strength and efficiency of the cellular batteries. By invigorating the mitochondria, SIRT3 and SIRT4 extend the life of cells, by preventing flagging mitochondria from developing tiny holes (or pores) in their membranes that allow proteins that trigger apoptosis, or cell death, to seep out into the rest of the cell.

“We didn’t expect that the most important part of this pathway was in the mitochondria,” says David Sinclair, an assistant professor of pathology at Harvard Medical School and a study co-author. “We think that we’ve possibly found regulators of aging.”

And last, the interesting personal background of the principal investigator David A. Sinclair (see also: Resveratrol goes to the clinic: a Pulitzer for David Stipp!) from the recent Technology Review portrait, The Enthusiast:

Sinclair says his bravado and drive come from his grandmother Vera, who fled to Australia in the wake of the failed 1956 revolution in her native Hungary. Her son, David’s father, changed the family name from Szigeti. “My grandmother is the black-sheep rebel of the family,” he says. “She gave birth to my dad at age 15 in 1939 - imagine the scandal then - and has lived with natives in New Guinea and eaten human flesh,among other things. She once got in trouble with the police for being the first person to wear a bikini on a Sydney beach. She’s a 60s bohemian who helped raise me and taught me how to think differently and question dogma.”

The last time you saw a science presentation with an overhead projector

For me, it was on SENS3, the presentation of Anun Hallen, who blamed only extracellular crosslinks (e.g. advanced glycation end products)