Three links in Aging, Regenerative Medicine & Healthy Lifespan Extension: 17 December 2013

1. DNA methylation age of human tissues and cell types by Steve Horvath: This is the type of relevant data mining study most bioinformaticians are dreaming of: you pull together a large body of publicly available datasets (CpG methylation) that are not too heterogeneous (Infinium type II assay on Illumina 27K or Illumina 450K array platform), derive robust statistical results (develop a multi-tissue predictor of age) and apply it on a medically relevant field (20 cancer types exhibit significant age acceleration, with an average of 36 years). Continue reading

Three links in Aging, Regenerative Medicine & Healthy Lifespan Extension: 8 December 2013

1. Is aging linear or does it follow a step function? A good & simple question on Quora that surprised even Aubrey de Grey. If you are a bioinformatician out there – looking for a new pet project – go pull together some data & try to plot it! Let me know if you have something. An interesting answer:

It’s exponential. Starting in your 20s, your probability of death doubles every 8 years, as does your probability of getting cancer. Of course, since we’re talking about high-impact, low-frequency events, they’re governed by a Poisson distribution (i.e. fairly random noise, manifest in “jumpy” changes). But there’s no planned step-function behavior.

If interested to know more, start with thorough fact-checking on things, e.g. on that probability mentioned above.

2. Developmental senescence: yeah, as in normal, physiological, embryonic development. In mammals. Reported by study_1 and study_2. Apoptosis has long been accepted as part of the healthy embryo’s toolkit, think limb growth and tissue remodelling. Now senescence follows.

Perhaps the most important ramification of the new work relates to its implications for the evolutionary origin of the senescence program. Most research to date has focused on senescence as a tumor-suppressive process, and it has been debated as to how evolution selects for programs that prevent a disorder that typically occurs after reproductive age (Campisi, 2003). The new work raises the possibility that senescence in the adult evolved from a primordial tissue-remodeling program that takes place in the embryo. In both settings, cells arrest in the cell cycle, partially share a common set of functional markers, have an active role in modifying the tissue microenvironment, and are ultimately recognized and cleared by the immune system (Figure 1). These features may have been adapted as part of an emergent adult stress response program that incorporated additional tumor suppressor mechanisms, such as those reliant on p53 and p16, to eliminate damaged cells and that may, in turn, contribute to organismal aging.

3. This anti-aging brain trust is the most interesting startup in Silicon Valley: I don’t care about hype or no hype but I do care about the fact that the sporadic news on Calico re-energetised the whole aging/lifespan extension field and community.

The timing may be just right for a project like Calico. And unlike the vast majority of Silicon Valley’s startups, the technology is addressing a need that is keenly felt by many of us. Most people are in a constant battle against aging and will pay exorbitant sums of money to slow down the rate that our bodies deteriorate.

“Historically, the whole field of aging research has been very underfunded Continue reading

How to build a colorful life around life extension using different skills: a personal story

Here’s an edited version of my Quora answer to the question: “Life Decisions: How do people who are talented in many areas decide what to do with their lives?

Let me provide a personal story illuminating one option Ruchira is talking about: “pick a complex challenge that you are passionate about, that will require many different talents to solve.

I picked the rather complex topic of aging and healthy lifespan extension at the age of 14-15 and it helped me to deep dive into a couple of different professions so far, consecutively, not concurrently though:

1. got a masters in biology and worked experimentally on the mitochondrial theory of aging as a thesis work, something related to looking for mutations accumulating with age in the hypervariable regions potentially downregulating the electron transport chain components encoded by mitochondria

2. realised that in order to understand what aging is (that is sg related to changes happening over time) I have to understand what time is and how it is structured that lead me to have another masters in analytical philosophy with a lot of modal logic involved, and my thesis work was entitled “Partial immortalization and the philosophical problems of human biotechnology and regenerative medicine”, basically delineating a technologically foreseeable scenario of unlimited life span and its social context

3. philosophy and timing lead me to journalism/blogging on aging and life extension and that is a separate skill set definitely, let alone an, independent, self-nurturing profession, discovered here my peers interested in the same thing

4. with the rise of stem cell research and regenerative medicine went back to the wet lab and started a PhD, did everything there except finishing the damn thesis, was mainly working on mitochondrial transfer between healthy stem cells and cells in oxidative stress, turns out the energetic reboost by healthy mitochondria can be an alternative way of how injected stem cells regenerate the injured/aged host tissue, to sum up experimental science gave me the insight that stem cells/regmed + mitochondria can be crucial in life extension technologies

5. blogging made me geeky and technologically involved and the rise of systems and omics biology made me realise that aging can be best understood by computational biology or by bioinformatics tools, built some stuff on genes related to aging as my first serious coding assignment

6. learned the basics of coding and turned myself into a bioinformatician in 2009, this is the last and so far most promising chapter in my quest, here I currently have at least 2-3 pet projects related to aging

So in order to understand aging and work on life extension I learned and practised wet lab biology, philosophy, journalism/blogging, coding and bioinformatics all motivated by the same, but continuously redefined aim, looking at it from many angles.

Jack of all trades, master of none? Mostly true concerning the fact that I had worked intensively in these particular fields only for 3-4-5 years. But since bioinformatics as a profession has now found me and since I’m in my late thirties I can’t help mastering it finally. :) Concerning personal investment into aging/life extension: that’s ~ 20 years already.

In a way being motivated & triggered by a big, complex, larger-than-life topic like life extension is a burden (might be harder to go into details when overshadowed by a big idea), but on the other hand it gives me a constant motivation and demand. As a bonus focusing on aging is a person-against-nature thing and not a person-against-person thing (like law as a profession) and somehow this always helped me not to take competitive situations too seriously and follow my inner compass.

Are life extensionists mainly driven by a desire to actually live a long time?

How do you interpret the following situation: we have a life extension technologist whose all endeavors is about pushing this issue to its very limits and making things possible but on the other hand this very life extensionist himself is not driven by actually living as long as he can.

It seems that SENS theorist Aubrey de Grey, who is chronologically 45, (BioBarCamp photo by Ricardo) is taking roughly the above position in a recent interview. Aubrey is a good and witty interviewee and of course the interpretation of what he is saying is strongly context dependent so here is the full question and answer:

Question: One hundred years of life can wear you down physically, but it can also wear you down emotionally… perhaps even existentially. For you, is a desire to live long accompanied by a desire to live long in a much-improved human civilization, or is this one satisfactory?

Aubrey de Grey: I’m actually not mainly driven by a desire to live a long time. I accept that when I’m even a hundred years old, let alone older, I may have less enthusiasm for life than I have today. Therefore, what drives me is to put myself (with luck) and others (lots and lots of others) in a position to make that choice, rather than having the choice progressively ripped away from me or them by declining health. Whether the choice to live longer is actually made is not the point for me.

Let’s see 2 possible and extreme interpretations of this answer (neither of them is my own interpretation) and I hope my readers can find fine-tuned arguments in between while thinking a bit about this still rather philosophical topic:

1., Saying that we want the process (a robust healthy lifespan technology) but not necessarily the product (a robust healthy lifespan) of our own business is a disaster Continue reading

Poll: How will the global economic crisis affect the chances of technological life extension within the next 25 years?

assuming we are heading into a global economic crisis…

Even ugly handwriting can fit the informal nature of SciFoo

I had problems with my handwriting since elementary schools, or at least my teachers had continuous problems with it. Even during my university years I was asked sometimes to read out loud my essays, papers to them otherwise risking bad grades. Maybe it’s because I am a hidden right-handed using my left hand for writing or maybe I am just too impatient over the slow pace of handwriting (needless to say computers mostly solved this problem).

On this George Dyson photo here you can see the SciFoo schedule in progress and I think you can easily pick the one with the ugliest handwriting on Aging and Life Extension:

Sergey Brin, Gly2019Ser & a real chance against Parkinson disease/aging!

It was already known that amongst the Google top people Sergey Brin is the one who is most interested in pushing biotechnology and the biomedical sciences: in his Stanford years he was interested in biology courses according to The Google Story, he married Anne Wojcicki (who graduted from biology at Yale), Google invested $4.4 million into 23andMe the pioneering personal genomics company co-founded by Anne, then Google invested into 23andMe competitor Navigenics too.

Now Sergey Brin added another, serious and personal reason to think that he is really, personally committed to the quick progress in the biomedical sciences: in his new blog – already a bit of an Internet history – called Too he disclosed that using the 23andMe personal genetics service he figured out something worrying about his and his family’s risk of Parkinson disease (his mother and her aunt are being already diagnosed with PD):

“I learned something very important to me — I carry the G2019S mutation and when my mother checked her account, she saw she carries it too.
The exact implications of this are not entirely clear. Early studies tend to have small samples with various selection biases. Nonetheless it is clear that I have a markedly higher chance of developing Parkinson’s in my lifetime than the average person. In fact, it is somewhere between 20% to 80% depending on the study and how you measure.

The G2019S mutation is actually the rs34637584 SNP and lies in the gene LRRK2 encoding leucine-rich repeat kinase on chromosome 12. The mutation affects the first codon of the gene and is a guanine (G)-to- adenine (A) substitution resulting known as a missense and  leads to a glycine – serine (hence the name) amino acid conversion in the protein product. Here is how the SNP position looks in the 23andMe browser using the sample family, the Mendels.

23andMe’s amazingly good corporate blog The Spittoon cited a recent article about the chances: Continue reading