Monday, 13 June 2011

Suspending Degeneration

In Life Ascending, Nick Lane gives hope to those who are not immortal by offering a couple of problems with Medawar's explanation for ageing, not least that when we talk of diseases (CVD, stoke etc....), associated with ageing, these are symptoms of ageing, not the cause of ageing itself

To put it another way, age may 'unmask' the disease, exposing 'aberrant' genes, but you might get to 120 and die of 'old age' rather than any disease for which you carry a genetic predisposition.

It is worth taking a step back here and noting that Lane explicitly states that Medawar's explanation for ageing is the one broadly held by the medical establishment.  In terms of an explanation it is quite linear - you're born, you get old, things wear out, you die.  At a basic level this is true, but we are dealing with biological systems which can adapt.  There is nuance here.

To take another step back, this 'linear' model strikes me a being analogous to the medical establishment's views on obesity.  The mindset is reactive and tinkers with symptoms without actually looking at deeper, ultimately hormonal factors, and again fails to consider our 'adaptive' capacity as biological entities.  So just as you are fat because you 'eat too much and do too little', you age because 'time has elapsed and you have worn your genes out'.  Both are static models of the human body following a 'normal' trajectory.

So what is the 'nuance' of ageing? 

This distinction between the symptoms of ageing and the cause of ageing was greatly highlighted by the work of  David Friedman and Tom Johnsone at the University of California.  They discovered a life-extending mutation in nematode worms.  Subsequently several other similar mutations were discovered in other nematode worms and in other species such as fruit flies and mice,
  • "Gradually a pattern emerged. Almost all the mutated genes encoded proteins in the same biochemical pathway...[i]n other words, there is an exceptionally conserved mechanism...which controls lifespan.  Mutations in this pathway not only prolong lifespan, but in doing so can postpone, even evade, the diseases of old age...The link between disease and lifespan,did not come as a surprise.  After all mammals suffer from a similar spectrum of age-related diseases, including diabetes, stroke, heart disease, blindness, dementia and so on."
Lane remarks that 'genetic diseases' are linked to old age rather than chronological time, and what is more, there was a surprising discovery that a mutation in one gene can suspend this whole degenerative process:
  • "All the diseases of old age, from cancer to heart disease to Alzheimer's disease, can in principle, be delayed, even avoided, by simple permutations of a single pathway...it should prove easier to 'cure' ageing and all age-related diseases with a single panacea that it will ever be to cure any one age-related disease."
Here is where Lane gets really interesting; digging as he does, deep in to evolutionary territory.  He notes the expense of growing to sexual maturation with the acknowledgment that it is better to 'forestall' sexual maturation in lean times:
  • "This means that environmental plenitude must be monitored and converted in to a biochemical currency that speaks directly to cells;  'There's plenty of food, now's a good time to prepare for reproduction.  Get ready for sex!'"
All this kind of stuff should be familiar to anyone vaguely familiar to Art Devany's work, but it is thrilling to see such conclusions being drawn across different branches of academia.  So by now you are probably wondering which biochemical signal heralds 'plenitude'?  The answer is Insulin (with several other hormones which Lane informs us work over time-scales of weeks or months), and in particular insulin-related growth factor (IGF)!

The consequence of this last point is quite incredible.  Your body is programmed for the ebb and flow of food as seasons change and providence unfolds before us. 

We read the usual 'yada yada' about signalling, but truly, your body is 'blind' - it doesn't see the world as 'you' see it.  It can't look out the window and see snow, or look in a calendar to know that it is winter.  It cannot see the ribs of cattle or the brown of dried grass to know famine and/or drought is stalking the land. 

The most basic filter that makes the world visible to your body is energy.  Think of the varied demands upon your energy reserves from something like a dip in cold water, which ramps up your metabolic furnace.  This demand will be slightly different to that of a season of cold weather.  The latter prompts you to move (shiver) to generate heat, and may well offer a longer term (but less intense), kind of impetus to move than migration or hunting.  Activity levels in pursuit of prey, or in escape from a predator, causes immediate and intense energy demand.  This is before we get to think about the energy available based upon macro nutrient composition... But all the time, your body is calculating....waiting for the optimal moment to make its move...to incite you to procreate at a time which offers the best chance of survival for your offspring.

Energy, and the flow of it; This is how your inner actuary builds a view and understands the environment it is inhabiting.  This is the driver with which we must engage to talk to our 'inner actuary':
  • "...when food is plentiful, the insulin hormones leap in to action, orchestrating a range of developmental changes , gearing up for sex.  If food is unavailable, these pathways fall silent and sexual development is postponed.  But silence does not mean that nothing happens....the absence of a signal is detected by other sensors, which in effect put life on hold.  Wait, they say, for better conditions, and then try for sex again.  In the meantime, the body is preserved in a pristine state for as long as possible."
If we can understand this signalling, this offers the very real chance we can, for a period of time at least, 'put life on hold'!

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