Transcript Document 7137192

BSG Annual Conference 2006
The Ageing Jigsaw: Interdisciplinary approaches to
understanding old age
7th-9th September 2006, University of Bangor, Wales.
The language and symbolism of
death and old age in bio-gerontology
by
John A. Vincent
1
Introduction
• Recent scientific interventions have achieved dramatic
increases in longevity amongst nematode worms, fruitflies and mice. It is suggested that these experiments
open the possibility of greatly extended human longevity.
• “We are now in the era of emerging ability to control our
actuarial destiny in response to the desire in humans
throughout history to live comfortably and to delay death
(Holliday 2001; Preston et al 1978).” (Carey 2003:220)
• This paper examines the impact of the culture of science
on the meaning of old age. In particular it examines
developments in understanding ‘cell death’ and their
potential impact on the meaning of old age.
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The sociological relevance of the issue
• Social constructionism has played a key role in dismantling old age
and exploring the possibilities that there are alternative ways to live
a good old age. Old age not simply a matter of biological
determinism.
• But what are the limits to social constructionism? Surely death and
the frailties of the fourth age are not social constructions?
• We can see that different cultures approach death in very different
ways; there are many myths and rituals that re-enact denials of
death. But every one dies. Similarly experience tells us that
everyone ages.
• However, it is a false distinction to see social constructions as
merely the products of a cultural imagination as opposed to scientific
facts which represent the truth about nature. Two ways around this:
• Psychological: W. I. Thomas “if people believe that something is real
it is real in its consequences”
• Phenomenological: We cannot observe the world without cultural
framework to name and categorise it.
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Accessing meanings of old age
• Cultural concepts are necessary with which to
understand and make sense of the world. But those
cultural concepts are produced in historical and
continuous process in which the social and the natural
environment are critical components.
• Cultural categories are established through boundaries contrasts which mark semantic space.
• To understand old age it is necessary to know its
boundaries, how to recognise it, and thus the markers
which indicate the boundaries between what is old age
and what is not.
• Meanings cannot be established in isolation, categories
are part of historical and cultural meaning systems which
interlock.
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Life and death
• Death contrasts with life. What is alive and what is dead and how do
we know? This boundary is highly contested and fraught with moral
dilemmas as to what is human and what is not. The medical
definition of death has shifted in recent history – contemporary
medical protocols for establishing death tend to use a concept of
brain death. Death has ceased to be a ‘natural’ event.
• Old age is the stage of life next to death. It takes it place in
developmental cycles of organisms from conception and birth to
decay and extinction. Ageing is then a concept parallel to maturation
defined by contrasting life cycle stages. It is worth noting that many
species don’t die. Mortality comes with sexual reproduction. But
death is a necessary boundary marker for the cessation of old age
and which is an important component in its meaning.
• At the level of the cell, cells were thought to be capable of
immortality until the discovery of the Hayflick limit. Thus cell
senescence came to mean reproductive senescence; the inability of
the cell to divide and replicate itself. There was the belief that old
age was programmed at the cell level. If we could modify that
programme perhaps we would not need to age. However, it turns out
to be much more complicated than that.
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Cell death
• ”In the course of these relocations of life, disease, and death
processes, the relationship between life and death has not remained
constant. Through analysis of the morphology, genetics, and
temporality of the body’s continuous cellular dying, the oppositional
relationship between life and death that existed for Bichat and those
who came after him was displaced by the vision of a multiplicity of
death that maintains tissue homeostasis, shapes development,
regulates the formation of the immune system, and serves as a
protective mechanism against oncogenesis. Thus, with the
localization and spatialization of death in the cell, death has become
for biomedicine not necessarily that which life is opposed but is
many cases, that on which life is dependent, or at least that with
which life and disease are inextricably bound… p.55
•
H. Landecker “On beginning and ending with Apoptosis” in Sarah Franklin and Margaret Lock 2003 Remaking Life and Death pp.23-60
James Currey: Oxford.
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Interview data
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In the small number of interviews I have conducted with scientists,
particularly bio-gerontologists I have systematically asked about three
processes ‘maturation’, ‘senescence’, and ‘apoptosis’. The differences in the
manner of response are illuminating.
With maturation there is a dismissive approach, respondents invent
something plausible but without interest or connection, they do not see it as
a relevant and important part of their lexicon – perhaps it might be more
relevant to biologist concerned with whole organisms and developmental
process – but for the cell scientists it was irrelevant.
Apoptosis on the other hand was responded to immediately and with
standard textbook answers. This was planned cell death. Many respondents
even quoted the standard textbook example of the apoptotic removal of
webs between the fingers in embryos.
However, the response to ‘senescence’ was interesting because there was
not a standard answer but the respondents thought there should be and
perhaps they were being caught out. The responses were full of linguistic
devises such as hesitation, circumlocution, restatements which indicated
unease or uncertainty from the respondents. Clearly the term was less well
institutionalized. Most produced the idea of cessation of cell division but
were uncertain whether that was sufficient and complete.
It was also clear from conversations with the scientist that many particularly
non English speakers were aware of the non-scientific origins and use of 7
the term senescence (c.f. Katz).
Faragher RG. (2000) “Cell senescence and human aging: where's the link?” Biochemical Society Transactions. 2000
Feb;28(2):221-6
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Ageing and disease
• There is another critical contrast that between natural processes and
disease. If old age is thought of as a natural process like puberty,
childbirth, or the menopause, it stands in contrast to disease.
• Thus a successful old age is to die of old age and not one of the
pathological risk factors associated with old age. Hence many
gerontologists talk about extending the health span
• Indeed many social constructionist medical sociologists have shown
how particular phenomena come have the disease label attached
and come under the scrutiny and control of medical institutions (Katz
and Marshall 2004).
• Bio-gerontologists are undermining this distinction between old age
and disease. These revisions come from two directions one from
evolutionary theory, the other from cell science.
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Evolutionary approaches
•
•
•
Evolutionary theories of ageing were developed by Medewar. His insight
was that the pressure for selection came in the early years of the life span
enabling species to successfully reach breeding age and produce offspring.
The selective pressures in older age, particularly beyond reproductive age
(but note grandmother hypothesis) were not so strong and hence it was
possible that genes for survival in youth also carried traits for decline and
senescence in old age. Modern genetics of old age indeed suggests that
particular genes have a range of functions which have positive and negative
impacts on risk factors and survival rates at different ages.
Tom Kirkwood using the sophistication of modern maths and computer
modeling to simulate evolutionary processes has developed the disposable
soma theory. This is the idea that there is a trade off between the energy an
organism expends on sustaining itself and the energy it puts into
reproducing the next generation. If it fails to develop an optimum balance it
will either wear itself out before it has a chance to produce maximum
progeny or it will live so long as to present a competitive threat to its own
offspring’s survival. He suggests that ‘in the wild’ specific genetic
mechanisms to die at a specific age are unlikely as rates of predation would
render such a mechanism unnecessary.
The logical consequence of this position is that, if people can avoid
predation and eliminate the risk factors of specific diseases, there is no
natural limit to the human life span.
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Cell science
•
•
•
From the perspective of cell science it turns out the ageing is pretty much
indistinguishable to the standard metabolic processes that happen in cells.
In addition to the enormously complex bio-chemical processes of the cell
cycle and or metabolism, there is a also highly complex repair and
maintenance processes which ‘clean up’, ’police’, protect the cell from
routine and accidental bio-chemical products of living.
When these mechanisms fail we can get disease in the form of tumours, or
when they are overactive we get diseases in the form of autoimmune
diseases (arthritis). Organ specific failures to repair which form the risk
factors in old age are related to declining efficiency is some of these
processes perhaps due to accretion of metabolic residuals over the life
span, which in turn of course might be related to life course and
environment factors.
The logic of this position is that if we could find ways to sustain the
efficiency of the processes which keep cells on the bio-chemical straight
and narrow we would both cure the diseases of ageing (and most others)
and prevent death. Indeed model programmes for researching such a
regime for immortality have been produced and are being advocated by a
minority with the biogerontological community. Thus this new biology within
cell science holds out the prospect that upregulating the metabolic process,
or repairing the damage it routinely does, will inhibit ageing and thus also
avoid the diseases of old age.
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Biology and the certainty of old and death.
• Harry Moody and Leonard Hayflick ask “Has any one
died of old age?”[i] Moody makes the significant point
that if you answer ‘yes’ to this question it means ageing
is a disease so a cure can be found for it and people
potentially will live for ever, and if you answer ‘no’ it
means people die of some other disease for which cures
can be found and thus people potentially will live for
ever.
• Mykytyn (2006)[ii] does an excellent job of
deconstructing the President’s Council on the Bio-ethics
of ageing demonstrating the rhetorical uses of ‘natural’
life spans as necessary to the separation of ageing from
disease and how ‘anti-ageing medicine’ challenges this
distinction by treating ageing as the subject of therapy.
• Thus we reach a position where the certainties of death,
disease and ageing as they are popularly understood (in
both the general public and in social gerontology)
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disappear under close examination.
Fragmentation of biogerontology
• Thus what can be observed with the developments in
contemporary bio-gerontology is an undermining of the
key categories through which we understand ageing and
old age. This is highly significant for the future given the
importance of biology and medicine in setting the cultural
meaning and the institutional framework within which
ageing is lived in Western society.
• But also what is going on is a fragmentation of biology.
The biology of ageing has moved from a minor nonprestigious corner of biology, to become centre stage in
the new biology which focuses on genetics, cell process
and the bio-chemistry of complex proteins.
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Genomics of ageing
• The major recent advances in bio-gerontology have resulted from an
increased knowledge about cell processes which stem in turn from
the genomics revolution and from the complex bio-chemistry of cell
processes.
• But it is important to appreciate that the contemporary science is a
considerable distance from popular understanding of genetics and
even that commonly found in popular science.
• Biological ageing is not all in the genes. There is no single gene for
ageing, or even a combination of genes. There are a large number
of genes with some association with longevity, or processes which
appear to lengthen or shorten the life spans of particular species.
But single gene, single trait models of the genome are obsolete.
There are enormously complex pathways by which genes get turned
on, express themselves, interact with one another, and initiate
hugely complex chains of protein synthesis and transformation.
• Sheer complexity creates a demand for new models and methods of
analysis.
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‘Ageing’ moves centre stage
• A leading biologist at the ICFGA said that “ageing turns out to be
about living: basically it is metabolism…”
• As a symbolic statement it tells us, the life and death are the same
thing, while culturally they may be conceptually opposites, in biology
the basic process of living is also dieing. The basic process of
consuming energy to stay alive creates the conditions for ageing
and death.
• However, for biology it means that ‘ageing’ is no longer a distinctive
process for which there is a distinct sub-branch of biology and
reflecting that knowledge base, gerontology as a single medical
specialism is having its exclusivity challenged. Understanding the
genetics and bio-chemistry of cell processes is at the fundamental
core of biology.
• This fragmentation is evident in my attempts to map the attendees at
the ICFGA in terms of their disciplines. It proved immensely complex
and the following diagrammes illustrate:
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Venn diagramme of mirco-biology disciplines at
ICFGA
16
Venn diagramme of medical disciplines at
ICFGA
17
The possibilities of life extension undermine the
contemporary cultural value of old age and old people.
•
•
•
•
•
Bio-gerontology largely positions itself in categorizing old age as a failure. In
defining it in terms of the body, it specifically foregrounds bodily failure as
the essential nature of old age.
In looking for ways in which a cultural revaluation of old age might occur, my
argument, developed elsewhere is that a healthy death is necessary for a
good old age (meaning the final part of life before death), otherwise old age
is always defined by its failure, i.e. dying.
In this work I have drawn on the social constructionist traditions out lined at
the beginning of this paper. If dying cannot be a positive event then nor can
old age.
The notion of a healthy death; one which escapes the apparatus, technical
and institutional, of the medical professionals and disease control, it has
been met with incredulity and incomprehension. The power of the medical
model is such that it is difficult to think about old age outside its frame.
But here I have argued that the biology of ageing is fragmenting. There is
no longer a single biological story of ageing. Does the biology offer
possibility of more positive models of ageing and old age? Does the
fragmentation leave space for other new perhaps liberating models of old
age? Here we come to the interesting metaphor of ‘apoptosis’ which I will
develop below.
18
H. Landecker “On beginning and ending with Apoptosis” in Sarah
Franklin and Margaret Lock 2003 Remaking Life and Death pp.23-60
James Currey: Oxford.
• “Although many commentators call the insistent presence
of narratives of human death in cell death science
anthropomorphism and comment on its “danger” to the
practice of science (Clark 1996; Debru 1998; Friedman
and Brunet 1995), I believe that these narratives and their
tensions point to a more complicated and more interesting
role for the cell in contemporary biomedical culture than
that of an irrational being incorrectly endowed with human
qualities. The cell is a site through which all kinds of
changing material, semantic, economic, and conceptual
relationships are played out: cell to body, cells to one
another, scientists to doctors, patients to laboratories It is
a site in which what it is to be cellular, in life, death, and
disease, is constantly being produced.” p.57
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Cell death
Biology defines a limited number of ways a
cell can age and die
• Senescence
• Apoptosis
• Necrosis
Like most things in contemporary biology,
this including the terminology is
challenged. Some others associated with
cancer and disease function (oncosis etc.)
20
One model of the relationship:
Soti C, Sreedhar AS, Csermely P.(2003) “Apoptosis, necrosis and cellular senescence: chaperone
occupancy as a potential switch” Aging Cell. 2003 Feb;2(1):39-45.,
21
Senescence
• Senescence is the cell in old age. That is how it
is thought of as metaphor even if the belief that
there is a specific direct link to organism ageing
is contentious. Variously in biology its meaning
has shifted from senescence as specific form of
decline, loss of efficient function in all aspects,
including the accumulation of ‘junk’. But
increasingly it is specifically used in the sense of
replicative senescence - the cessation of mitosis
(cell division). This links to telomere theories.
But recent research evidence suggests that
revival from senescence can occur.
22
Senescence imaged
• A new test developed by LBL
researchers uses blue stain to
detect the presence of
senescent cells. The assay top
left shows young tissue with no
presence of blue; top right is
young sunburned tissue, also
negative. Older tissue cells,
pictured in the bottom four
assays, contain blue areas
revealing evidence of the
existence of senescent cells.
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Necrosis
• Necrosis is accidental death. The cell is injured
ruptured and spills it contents to the detriment of
other cells in its vicinity and causing
inflammation. The damage can be mechanical
but it might also be poisoning or other fatality.
‘Act of God’ in the insurance world. The
purveyors of immortality always point out that
mortality can never be reduced to zero, there will
always be fatal accidents. Some biologists have
suggested the boundary with other forms of cell
death may not be as clear cut as this definition
suggests.
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apoptosis
• But what about apoptosis? The biology text books and popular
science media have it off pat as suicide. Sometimes called murder
when it occurs as a result of extra cellular stimuli, but I found only
one use of the term euthanasia. However, Apoptosis is clearly good
death. It is a vital part of life and the continued health of the
organism. Here is a model of good death. It is the individual (cell)
playing its part in the overall life of the body. Its death at the right
time and the right place is a necessary and desirable outcome for
the health of the multi-cellular soma (peoples bodies).
• The metaphor is clear, death is an essential part of life. Conversely
universal immortality or systematic attempts to increase the life span
will transform life and essential human qualities. This may or may
not be desirable but a radical departure from humanity, as it is
currently understood and experienced, is inevitable with the
elimination of old age and death. It will not be more of the same
experience of age but frozen in time, but rather an essentially
different semi-natural entity of uncertain meaning.
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The final stage of apoptosis; cleaning up after the
death
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Death defines the category ‘old age’
• ‘Age’ is both a verb and a noun: it stands for both a process and
also a set of categories. Some parts of the trajectory of social and
biological change over time are identified as ‘ageing’. It is
understood as a sequence of stages and statuses to which specific
age based normative expectations are attached. The specific
content of those processes and categories are contested; their
meanings are not fixed. The future life course may have different life
stages; new divisions in the 20C have included teenager, and ‘third
ager’. There may also, in addition or instead be a breakdown in the
structure of the life course with less definite stages or sequences.
• As old age becomes increasingly ‘biologised’ it is in fact, in parallel
to biology, becoming fragmented and loosing coherence as a
concept. There are many biological stories of ageing, and more are
being produced, - there is not a single story of the biology of human
ageing.
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Positive images of ageing from the new biology
• Negative cultural constructions of old age spill into biology but are
transformed; biological concepts become transformed when used in
popular discourse to legitimate ageist practice.
• This has been illustrated by the way the concept of senescence
entered and has been transformed in biogerontology along with the
way debates over different kinds of cell death – apoptosis, and
necrosis – form a repertoire through which ageing and death can be
imagined.
• With the fragmentation of biology and the concomitant lack of single
authoritative biological voice telling us what ageing is, there become
room for alternative visions for the nature of old age and the future
possibilities for ageing. There are at least two possible contenders.
• Firstly, the good old age as a positive final stage in life concluded by
a healthy death. And we now have a model of healthy death from
biology, namely apoptosis.
• Secondly there is the good old age as an enhanced/super human
being/ cyborg with death defying capabilities.
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• A copy of the paper and the power point
presentation is available on my personal
website.
• http://www.people.exeter.ac.uk/JVincent/B
angor/
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