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But if a man has an interactive blog with a quality readership even an officially unpublished text could be useful, so please read my draft in its final form and think about it.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
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 milieu1. Answers could be different – tissue by tissue. One candidate mechanism of intrinsic stem cell exhaustion with ageing is the progressive telomere shortening at the end of the chromosomes during divisions.
Telomerase orchestrates telomere lengthening, and the enzyme’s activity was found to be increased in several stem cell subtypes such as embryonic and neural stem cells. However, in case of satellite cells (skeletal muscle stem cells), telomeres seemed to be well maintained and intrinsically young in old mouse muscle (Matthew O’ Connor, UC Berkeley) suggesting that some other mechanism is responsible for the regenerative decline with age.
The real reward of a science talk if it inspires to form new, testable questions: like that of Michael Conboy‘s presentation on the immortal strand hypothesis. The hypothesis in its updated form posits that the propensity of stem cells to give rise to cancer in later life can be minimized if stem cells, during the process of self-renewal, retain those DNA strands with the fewest mutations acquired during nuclear DNA replication2. The emerging question is whether the mitochondrial DNA can undergo a similar non random segregation and clonal expansion in stem cells, and if so, how this could be addressed experimentally.
The life-long deterioration of mitochondrial DNA and the accumulating oxidative damages have been proposed to be a significant factor in the ageing process. It is a good question why only 13 members of the electron transport chain remained encoded (plus 22 tRNAs and 2 ribosomal RNAs) by the human mitochondrial DNA throughout the lengthy years of evolutionary trade-off between the mitochondrion and its host nuclear DNA.
The idea of allotopic expression of the mitochondrial protein genes in the nucleus is a potential mitochondrial repair concept3. The main obstacle of allotopic expression on the cellular level is the extreme hydrophobicity of the proteins, which prevents their import into mitochondria. One solution could be the use of inteins whose insertion into such transgenes could greatly reduce the hydrophobicity, and, at the same time, enable import (Tonio Enriquez, Univ. Zaragoza). Another option is to introduce neutral DNA polymorphisms into the nuclearly expressed gene, which brings a key subunit (ATP synthase 6) within the threshold for importability (Mark Hamalainen, Cambridge, UK). Allotopic expression as a therapy is extremely challenging technically. The safe somatic gene therapy approach that would be necessary for the mitochondrial repair of trillions of cells that made up the human body is not within range.
Scientists with mission
Missions in science and technology are no other than macro problems that need to be solved, beyond the ‘publish or perish’ horizon. One such mission is to find an all pervasive cancer therapy and probably the oldest mission is to understand aging in order to increase healthy lifespan. As we know more and more about how deeply aging and cancer are interrelated4, it might turn out that those old missions are really the two sides of the same coin.
The convergence of different science motivations can eventually lead to a yet unseen multifaceted scientific co-operation and amplify the efforts of extending our healthy human lifespan. In a wider sense, a well-funded life extension community might finally revise the notion of the basic human right for life. On the SENS3 conference, the emphasis was not on the big non-ideological mission (that was taken for granted), but on the scientific-technical and cultural details, which is a sign of maturity.
＊Third Strategies for Engineered Negligible Senescence (SENS) Conference, Queens’ College, Cambridge, UK, 6-10 September 2007, http://www.sens.org/sens3/
1. Rando TA. Nature 441:1080-6 (2006)
2. Rando TA. Cell 129:1239-43 (2007)
3. de Grey AD. Trends Biotechnol. 18:394-9 (2000)
4. Finkel et al. Nature 448:767-74 (2007)