The following was written by my colleague Robert Pappas on a debate that took place recently at Oxford University between two prominent British scientists on “defeating aging.” The writing largely reflects my own sentiments and I am including it here as a guest commentary. Robert Pappas is the Producer/Director of the recently-released film To Age or Not to Age.
On April 25th, Aubrey de Grey participated in a debate with Prof Colin Blakemore – neuroscientist and ex head of the Medical Research Council, UK’s largest funding body for bio medical research – at Oxford University’s Sheldonian Theatre. The debate’s title was: “Resolved this house wants to defeat aging entirely” and was to cover the feasibilityand desirability of bringing aging under medical control.
(Videos of the debate are available online. See Part I – Main Debate and Part II – Audience Q&A.)
After watching the video of the debate; among other things, it strikes me that the title itself helps obscure the nature and process of the scientific research currently underway to extend healthspan, and by implication, lifespan.
The problem waxes ironic. To a large degree, Aubrey became ‘famous’ by uttering the following on camera: “I’m claiming that the first person to live to a 1,000, subject of course to global catastrophes, is actually, probably only about 10 years younger than the 1st 150 year old, and that’s quite a thought.”
On the one hand, Aubrey’s thesis is provocative and possibly true – but there is a downside to such a framing of the discussion. The viewer or reader reacts – ‘What, 10 years after 150, what? a 1,000 years, people from the middle ages would be alive, what? population, resources? Bombs? – who wants to live that long, the world sucks now, ahhhhhhh….!’ I personally observed similar reactions in a portion of the audience who watched my film “To Age or Not To Age.”
Professor Blakemore’s debate responses fell along the above lines, like an opposing pundit with several conventional wisdom talking points.
But Aubrey’s prediction hampers what could be an intriguing discussion about trajectory of the scientific understanding and the advances.
When I first interviewed Aubrey De Grey several years ago, he used the phrase ‘aging trance’ to describe people’s mental paradigm with regard to the phenomenon of aging. Although I didn’t feel the phrase was perfect, he made a valid point.
When you delve into the subject of extending human lifespan via the frame of people living a thousand years, all kinds of prejudices color what the questions are and how they are asked. Blakemore raised concerns about neurological memory, how people would spend their time, human motivation, population. He made the further point about the complexity involved, how a war on this or that disease waged 30 years ago still hasn’t produced a solution, stuff like that. All somewhat true, but also misleading.
One simply cannot adequately probe the subject of future advances when that discussion begins from the point of view of a thousand years. Firstly, the process itself is, by definition, incremental. Supposing what your memory would be like at 1,000, indeed one’s mental framework, is ludicrous.
Further, judging the speed of scientific advancement in the future by pointing to the slow pace of the past is a superficial analysis. Scientists are asking questions that they couldn’t imagine 5 years ago. Techniques for finding multiple needles in haystacks simply didn’t exist in the near past. What is more – and I think this is crucial – in the midst of huge complexity, scientists are finding nexus genes and nexus points which cause a cascade of downstream events. In other words, if you intervene at the right spot in the right way, the vast complexities resolve themselves.
Then there is the idea unintended consequences. There are always unintended consequences. Are they always bad? Is every mutation bad?
For his part in the debate, Aubrey didn’t give clear examples of feasibility or cite several recent advances. There is much that is unknown; but, the questions being asked, and the thread of recent results derived from those questions is striking. Moreover, simple observations about how quickly communication has changed (smart phones and the like) compel one to surmise that the integration and speed of scientific research will increase.
So, the discussion of this topic must be from the point of view of the moment at hand, not about the dim distance. Right now, scientists can extend the health span and lifespan of animals and humans through a combination of lifestyle changes, and by tweaking a couple of fairly well understood molecular pathways having to do with nutrient signally and cellular upkeep, particularly, the Mtor and Sirtuin genes. It is happening now. In the wings, new understandings about adult stem cells, cell signaling, senescent cells, DNA repair, mitochondrial function and the epigenome point to a vast horizon.
When we speak from the point of view of 1,000 years, it seems impossible that humanity won’t destroy itself by then. But then again, change is incremental but does happen. So maybe we won’t.
You may find Doctor Colrs article on supercenturians and amylodosis of interest.
Ref.: L. Stephen Coles, Robert D. Young, Supercentenarians and transthyretin amyloidosis: The next frontier of human life extension, Preventive Medicine, 2012, DOI: 10.1016/j.ypmed.2012.03.003; [PDF] (open access)
experimental drugs (such as Tapamidis meglumine, approved in Europe under the trade name Vyndaqel) exist that may eliminate amyloid. These drugs are being studied for young persons with pathological amyloidosis. Could they become the first drugs to extend human lifespan beyond current theoretical limits?
Aging Cell. 2011 Feb;10(1):10-7. doi: 10.1111/j.1474-9726.2010.00642.x. Epub 2010 Nov 10.
At the crossroads of longevity and metabolism: the metabolic syndrome and lifespan determinant pathways.
Fadini GP, Ceolotto G, Pagnin E, de Kreutzenberg S, Avogaro A.
SourceDepartment of Clinical and Experimental Medicine, University of Padova, Medical School, Padova, Italy. email@example.com
The metabolic syndrome is becoming increasingly prevalent in the general population and carries significant incremental morbidity and mortality. It is associated with multi-organ involvement and increased all-cause mortality, resembling a precocious aging process. The mechanisms that account for this phenomenon are incompletely known, but it is becoming clear that longevity genes might be involved. Experiments with overactivation or disruption of key lifespan determinant pathways, such as silent information regulator (SIR)T1, p66Shc, and mammalian target of rapamycin (TOR), lead to development of features of the metabolic syndrome in mice. These genes integrate longevity pathways and metabolic signals in a complex interplay in which lifespan appears to be strictly dependent on substrate and energy bioavailability. Herein, we describe the roles and possible interconnections of selected lifespan determinant molecular networks in the development of the metabolic syndrome and its complications, describing initial available data in humans. Additional pathways are involved in linking nutrient availability and longevity, certainly including insulin and Insulin-like Growth Factor-1 (IGF-1) signaling, as well as FOXO transcription factors. The model described in this viewpoint article is therefore likely to be an oversimplification. Nevertheless, it represents one starting platform for understanding cell biology of lifespan in relation to the metabolic syndrome.
Of side note is the location Padova Italy
Home of Luigi Cornaro and the 500 year old book Discorsi Della Vitta Sobria (Discourses on the Sober Life)