Why can't we live forever?
The only certainties in life, said Benjamin Franklin,
are death and taxes. Don't expect either to disappear anytime
The prospects for a longer life currently seem rosy, at least if
you are a laboratory mouse. This year has seen headlines about
mice, engineered to produce lots of antioxidants, who can live 20
per cent longer than usual, and equally impressive gains for animal
altered to produce high levels of a peptide hormone known as Klotho
(after the minor Greek deity). Ultra-low-calorie diets, big doses
of vitamin E, and even transferring ovaries from a younger mouse
into elderly females also seem to extend lifespan. Shepherds may
say that sheep are just looking for new ways to die, but mice seem
to be susceptible to almost anything that can make them live a bit
So what are the prospects for a rather larger mammal that
normally lives 70-80 years, rather than the mouse's two, and very
occasionally makes it to 120 before keeling over? Will what works
in mice work in humans?
There are well-publicised optimists who think it will. The most
often quoted is Aubrey de Grey of Cambridge, proponent of a big
expansion of research on what he has called Strategies for
Engineered Negligible Senescence. He is also one of the leading
lights of the Methuselah Mouse Prize, which is offered to the
scientific team that develops the longest-lived mouse.
But for all his energy and revolutionary zeal, Professor de Grey
is not actually doing the research - his day job is as a
computer expert in a genetics lab. And many researchers in
biogerontology are sceptical about his predictions. That scepticism
came through recently when Tom Kirkwood of the University of
Newcastle's Institute for Ageing and Health asked in 'Nature': "Why
must advocates of life extension make preposterous claims about
imminent longevity gains if they are to gain public notice?"
Professor Kirkwood is the author of the influential 'disposable
soma' theory of ageing, that the body decays because there is
little genetic interest in keeping it going beyond reproductive
age. This means that he sees no programmed limit to lifespan, in
mice or people. Ageing is a biological sin of omission, not
commission. So perhaps we could block whatever is doing the damage.
But, he stresses, "this does not imply that major increases in
lifespan are imminent. As we grow older the accumulated burden of
molecular and cellular damage increases and the going gets
Others in the field tend to agree. One reason is simply that
ageing is very complex and we do not know enough to make sensible
predictions. Caleb Finch of the University of Southern California
says: "I have a simple view: we don't know what we don't know about
ageing processes. So, what can be said on future longevity?"
Linda Partridge of University College London's Centre for
Research on Ageing, well known for work on fruit flies, backs
Professor Kirkwood. In any case, she adds, "I think that we should
be working to promote health during ageing rather than increases in
lifespan per se." Either way, she believes that "progress will be
gradual and based on existing promising areas of work, rather than
saltatory and based on unproven approaches".
Her colleague David Gems, who works on nematode worms, is
optimistic that the basic biology of ageing will be understood in
the next decade or two. But he stresses that how easily this
translates into treating or preventing ageing-related diseases
depends on what ageing really turns out to be: "There's a huge
margin of uncertainty." He suggests that cancer treatments are a
better historical guide than, say, antibiotics - and most
cancers remain incurable.
Martin Brand of the Medical Research Council's Dunn Human
Nutrition Unit in Cambridge also urges caution. "There have been
spectacular increases in lifespan caused by simple treatments and
mutations in model organisms," he concedes. But he is mindful that
flies and mice in the laboratory tend to live shorter lives than
wild strains. "I worry that these results can be explained as
putting right bad husbandry of the model organisms rather than
affecting ageing itself."
An investment too far?
However, the most basic argument against major extension of
lifespan for humans is a general one: that the eventual triumph of
entropy can only be delayed, not denied. Doug Wallace of the
University of California, Irvine, is an expert on how damage
accumulates in the energy-generating organelles, the mitochondria,
through the action of mitochondrially generated reactive oxygen
species, one of the main classes of free radical.
They damage not only the enzymes that generate energy but also
the mitochondrial DNA (mtDNA) that preserves the information needed
to repair the organelle. "Once the mtDNA becomes sufficiently
compromised, the mitochondrial power plants go off-line and the
cellular, tissue and organ systems fail," he says.
But while Professor Wallace believes mitochondrial degradation
is crucial, he does not believe that preventing it would open the
path to immortality. Instead, he reads the mitochondrial story as
an example of a broader principle.
He argues that lifespan is determined by the balance between the
processes that degrade our bodies' systems, and the investments our
cells can make in maintenance and repair. Those investments cover
both the DNA coding for the machinery needed to monitor and correct
cellular damage, plus the allocation of resources, particularly
energy, to actually make the repairs (including repairs to DNA
itself). "It follows that the longer the individuals wish to extend
life the greater the resources that will be needed to achieve the
end," he says. So in the end the cost will exceed the benefit.
In other words, fix the damage to the mitochondria, and
something else will bring the system to a halt instead: "As each
life-limiting process is countered, some other process will become
So while all these researchers believe the current results are
valuable for advancing understanding of ageing, and age-related
diseases, they do not think they hold the key to a society where
death comes only through accident or ennui.
Professor Kirkwood draws an athletic analogy: "No one thinks the
current world record for the mile represents the limit to how fast
this distance can be run. The record can always be broken. But no
one seriously expects the mile to be run in two minutes any time
How to live longer
Eat less: Research on animals has shown that
the only surefire way to extend life is through dietary or
calorific restriction - eat just enough to stay alive. You
won't have energy to do much, though.
Refrain from sex: In many species, having sex
seems to shorten lifespan. Resist temptation and you might be
blessed with more time in which to regret not enjoying yourself
Be popular: Good social networks, happy
marriage and close family contacts promote longer life.
Choose your parents: There appears to be a
genetic contribution to longevity - long-lived parents tend to
give rise to long-lived offspring. As George Sheehan put it to
would-be athletes: "choose your parents carefully".
Kirkwood T. Time of Our Lives: The Science of Human Ageing.
Oxford: Oxford University Press; 2002.
Wallace DC. A mitochondrial paradigm of metabolic and
degenerative diseases, aging, and cancer: a dawn for evolutionary
medicine. Annu Rev Genet 2005;39:359-407.
Bordone L, Guarente L. Calorie restriction, SIRT1 and
metabolism: understanding longevity. Nat Rev Mol Cell Biol