Experimental Gerontology 37 (2001) 1±7

www.elsevier.com/locate/expgero

Aging Research Worldwide

UK research on the biology of aging
Aubrey D.N.J. de Grey*
Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK
Received 6 August 2001; received in revised form 21 August 2001; accepted 21 August 2001

Abstract
Only a few years ago, it could fairly be said that biogerontology research in the UK was in a sorry state. With the exception of
the evolutionary biology of aging, which was revolutionized by Britons in the 1950s and in which the UK has remained
paramount ever since, the number of research groups whose main focus was biogerontology had waned to single digits, and
even those groups were generally very small. This situation has been transformed during the past decade, with the result that the
UK arguably leads Europe in this ®eld, in terms of both the quality and the quantity of its output. Moreover, the health of UK
biogerontology research seems secure for the foreseeable future. Its one potential Achilles heel is the overemphasis on
compression of morbidity as a goal, since further compression is highly unlikely to occur and is anyway inconsistent with
the public's demonstrated desires. q 2001 Elsevier Science Inc. All rights reserved.
Keywords: Aging; Biogerontology; United Kingdom; Funding

1. Introduction
Is there such a thing as biogerontology? This ostensibly rhetorical question has become hard to answer in
the UK in recent years, as work on age-related physiological decline has become interdigitated with ®elds
once viewed Ð by biogerontologists, but especially
by their own workers Ð as quite distinct. The refrain
ªI'm not really a gerontologist, but¼º is heard almost
comically often at British aging meetings. This is a
natural occurrence, given that the boundary between
aging and age-related diseases is extremely fuzzy (if it
exists at all), but in this gerontologist's experience, it
has happened more abruptly in the UK than elsewhere.
Not only is it a natural occurrence, it is an exceptionally good thing for biogerontology in respect of its
* Tel.: 144-1223-333963; fax: 144-1223-333992.
E-mail address: ag24@gen.cam.ac.uk (A.D.N.J. de Grey).

standing in biology at large. The vast complexity of
the aging process, in some ways outstripping even that
of development, has traditionally discouraged young
and/or successful biologists from becoming involved
in its study, for fear that they (and their careers) will
become mired in uninterpretable data. This has, in
decades past, given rise to the complementary prejudice that those who do study the biology of aging do
so because they could not compete in more tractable
sub®elds of biology. In short, biogerontology has not
been respected by biologists in general. This was as
true in other countries as in the UK, and is being
progressively dispelled there as here; again, however,
the abruptness of that process in the UK in the past
few years is striking. The bulk of this article is a
survey of the many examples that comprise this
phenomenon. Several such researchers focus more
on speci®c age-related diseases than on `aging itself';
this again is a step forward, since research into either
area can (and frequently does) inform the other.

0531-5565/01/$ - see front matter q 2001 Elsevier Science Inc. All rights reserved.
PII: S 0531-556 5(01)00163-2

2

A.D.N.J. de Grey / Experimental Gerontology 37 (2001) 1±7

A major driving force that has brought about this
change is the one that might be guessed, money, and
especially an improvement in the structure of how it is
disbursed. Two initiatives Ð one governmental, one
by a charity Ð have dominated the transformation of
UK biogerontology; they will be described below.
The one area of UK biogerontology that has
remained healthy throughout the post-war period is
the evolutionary biology of aging. Here, too, however,
a transformation has occurred, with specialists in the
`why' and the `how' of aging interacting more intensively and productively than ever before. Examples of
this will also be noted below.
The number of groups now working on aging or
age-related disease in mammals is now so great that
an article of this length cannot be comprehensive;
accordingly, I have preferentially cited below those
groups with whose work I am most familiar, and I
apologize to those whose work is omitted. However,
I hope to have ful®lled the major purpose of this
survey (and of this series on Aging Research Worldwide) by describing the major themes in which
research on biogerontology in the UK is particularly
strong.
2. Research on the evolutionary biology of aging
The post-war revolution in our understanding of
why aging has evolved, or not been evolved away,
was due principally to the insights of the British
researchers Medawar and Williams (Medawar,
1952; Williams, 1957) and is an area of which the
UK has remained consistently at the forefront (Hamilton, 1966; Kirkwood and Holliday, 1979; Charlesworth, 1993; Partridge and Barton, 1993). A
particularly welcome development in recent years is
that research groups originally dedicated mainly to the
theoretical aspects of this topic have become increasingly active on the experimental side, thereby
producing work that combines the best of both (e.g.
Martin et al., 1998; Sgro and Partridge, 1999). The
evolution of aging, like that of any other aspect of life
subject to Darwinian selection, occurs ultimately at
the molecular and cellular level; hence, evolutionary
biogerontologists who are prepared to broaden their
expertise to include molecular and cellular gerontology will be better equipped to test their (and others')

ideas. As a result they will progressively eclipse any
who remain wedded to an approach based exclusively
on mortality data; there is evidently no danger of the
UK evolutionary biogerontology community falling
into the latter category.
3. Invertebrate model organisms
Compared to many other countries, a relatively
small proportion of UK biogerontology is focused
on the standard invertebrate models (¯ies, worms
and yeast). Exceptions are the group of Partridge
(see above), working with Drosophila, and Gems
(e.g. Gems and Riddle, 2000), working with C.
elegans. Both groups are based at University College
London, and they have recently collaborated to
explore the remarkably similar in¯uence of the
insulin/IGF signaling pathway on aging in the two
organisms (Clancy et al., 2001). S. cerevisiae aging
is researched by the groups of Smart (e.g. Powell et
al., 2000) in Oxford, Piper (e.g. Harris et al., 2001) in
London, and Morgan (e.g. Mankouri and Morgan,
2001) in Liverpool.
4. Research on mechanisms of aging in mammals
Though evolutionary biogerontology has remained
pre-eminent in the UK, the number of researchers
involved in it has not greatly increased in recent
years. This certainly cannot be said of molecular
and cellular gerontology.
4.1. Oxidative damage
Several groups, both long and newly involved in
biogerontology, work on the etiology of oxidative
stress and damage in aging. Among the longest standing are those of Merry (e.g. Lambert and Merry,
2000), focused on caloric restriction in rodents, and
Jackson (e.g. McArdle et al., 2001), with speci®c
interests in age-related muscle dysfunction; both
groups are based in Liverpool. A valuable complement to Merry's work is that of the group of Speakman, based in Aberdeen, who study the relationship
between metabolic rate and lifespan in mice and other
small mammals (e.g. Selman et al., 2001).
The main origin of oxidative damage, including

A.D.N.J. de Grey / Experimental Gerontology 37 (2001) 1±7

that leading to aging, is generally agreed to be the
mitochondrion. It is therefore essential for biogerontology to involve researchers with a detailed understanding of how this most complex of subcellular
structures functions and malfunctions. The
Cambridge group of Brand, long prominent in bioenergetics in general and mitochondrial proton leak
in particular, has recently broadened its interest in the
role of mitochondria in aging (e.g. Brand, 2000).
Additionally, Turnbull's group in Newcastle
studies the deleterious effects of mitochondrial DNA
mutations in aging and age-related disease (e.g.
Cottrell et al., 2001), as well as in early-onset
mtDNA-linked diseases.
A target of oxidative damage that may be just as
important as DNA is proteins; this damage typically
results in the production of carbonyl moieties, which
are highly reactive and can cause protein±protein
cross-linking. One of our most powerful natural
defences against this process may be the dipeptide
carnosine, which is present at millimolar levels in
many tissues. The UK is fortunate to be home to
Alan Hipkiss, whose expertise in carnosine biochemistry is second to none and whose work is increasingly
revealing how carnosine exerts its effects (e.g. Hipkiss
et al., 2001).
4.2. Cellular senescence and nuclear DNA damage
Cellular senescence, the sub®eld of biogerontology
that has perhaps enjoyed (or suffered?) the highest
public pro®le in recent years, is a prime example of
the recent resurgence of British aging research, with
the sole exception that its growth somewhat predated
that of most other disciplines. Before about 1990 only
one group, that of Shall, was highly active in the
cellular senescence ®eld in the UK (e.g. Karatza et
al., 1984); now, by contrast, we can boast highly
productive home-grown research groups in numerous
locations around the country (e.g. Bridger et al., 2000;
Wyllie et al., 2000; James et al., 2000), as well the
group of von Zglinicki, previously based in Berlin
(e.g. von Zglinicki et al., 2000) but recently transplanted to Newcastle. These are in addition to work
on telomere structure and function not directly
connected with aging, such as that pursued by Jackson's group in Cambridge (e.g. Teo and Jackson,
2001).

3

It is now widely appreciated that other forms of
chromosomal damage, particularly double-strand
breaks, can trigger cellular responses very similar to
those associated with telomere shortening. This has
accentuated the interest of biogerontologists in DNA
damage over and above its role in cancer, and conversely the interest of DNA damage specialists in aging.
The work of Shall's group must again be noted as
having led the way in this regard, with their interest
in the role of poly(ADP-ribos)ylation in DNA strand
break repair (e.g. Durkacz et al., 1980). This is the
main focus of the group of Burkle (e.g. Beneke et al.,
2000), which, like that of von Zglinicki (see above),
has recently transferred from Germany to Newcastle.
Prominent among groups whose focus on DNA
damage and repair has only recently become integrated into biogerontology is that of Cox (e.g.
Ongkeko et al., 1999), based in Oxford and now
researching the molecular basis of Werner's
syndrome (e.g. Rodriguez-Lopez et al., 2001).
4.3. Aging of speci®c organ systems
The age-related decline of the immune system has
become a particularly strong branch of UK biogerontology in recent years. Groups involved include those
of Aspinall (e.g. Aspinall and Andrew, 2000), Akbar
(e.g. Plunkett et al., 2001) and Dunn-Walters (e.g.
Banerjee et al., 2000) in London, Lord (e.g. Butcher
et al., 2000) in Birmingham, Goyns (e.g. Lavery and
Goyns, 2001) in Sunderland and Barnett (e.g. Hyland
et al., 2001) in Coleraine, Northern Ireland. Aspinall's
group stands out among all UK biogerontology workers Ð not only those involved in immunosenescence
Ð as maintaining an interest in the actual reversal,
rather than the mere retardation, of age-related
decline, something that is also a major focus of the
present author (de Grey et al., 2001).
The heart is an organ whose aging is distinctive in
several important ways: for example, it loses cellularity without losing mass. Boyett's group in Leeds is
prominent in research on the mode of action of the
heart's pacemaker, the sinoatrial node (e.g. Boyett et
al., 2000).
Skeletal muscle, on the other hand, loses considerable mass during aging, with multifarious downstream
consequences. Aging of muscle is the focus of the
groups of Jackson in Liverpool (e.g. McArdle et al.,

4

A.D.N.J. de Grey / Experimental Gerontology 37 (2001) 1±7

2001) and Smith in Birmingham (e.g. Smith et al.,
2000).
The eye suffers from several major types of aging,
of which the most universal is macular degeneration.
The group of Boulton in Manchester studies aspects of
this process (e.g. Beatty et al., 2001). Glaucoma,
another extremely widespread disease of the aging
eye, is studied by the group of Webster in Liverpool
(e.g. Grierson et al., 2000).
An area often neglected due to its non-life-threatening nature, but no less deserving of basic research for
that, is urinary incontinence. This is studied by the
group of Ferguson in Cambridge (e.g. Burton et al.,
2000).
Groups involved in studying the aging of the
nervous system include those of Cowen (e.g.
Gavazzi et al., 2001) in London, Edwardson
(e.g. Singleton et al., 2001) in Newcastle, Davies
(e.g. Fotheringham et al., 2000) in Manchester and
Franklin (e.g. Hinks and Franklin, 2000) in
Cambridge. Of all aspects of aging, this is perhaps
the one where the overlap with diseases often
regarded as distinct from `aging itself' is least
clear, so highly relevant work on neurodegeneration
by UK groups too numerous to list here must also be
noted.
Last but not least, the various components of the
extracellular matrix are the subject of research by
several groups. A prominent example is that of
Clark in Norwich, which studies cartilage aging leading to osteoarthrosis (e.g. Dean et al., 2000).
5. Funding of biogerontology research in the UK
As noted in the Introduction, the `growth spurt' of
UK biogerontology has occurred at least in part
because of the improved environment for obtaining
funding for such research. Much of the credit for
this must go to the major charity funding biogerontology research, Research into Ageing (RiA). Founded a
quarter of a century ago, it has enjoyed a surge of
®nancial success in recent years under the inspirational leadership of Elizabeth Mills, with its income
rising nearly threefold between ®nancial years 1994/
1995 and 1999/2000. This money has been used to
fund research into all the aspects of aging mentioned
in Section 4.3 and more. It has recently merged with

the much larger, but hitherto not biology-oriented,
charity Help the Aged, a move which is set to provide
further sharp increases in its budget for the next two
years at least. Mrs Mills has now stepped down as its
head and has been succeeded by Dr Susanne Sorensen, under whose direction we can be con®dent that its
in¯uence will continue to be considerable.
Partly as a result of RiA's success, an effort was
begun in 1996±1997 to address the problem, so familiar to biogerontologists, that our ®eld falls between
the two stools of medicine and basic biology. (The
UK situation in this regard is exacerbated by our
lack of a governmental organization speci®cally
focused on aging, equivalent to the United States'
National Institute on Aging.) This resulted in the
SAGE (Science of Ageing) initiative, whereby the
BBSRC (Biotechnology and Biological Sciences
Research Council), the government agency with
responsibility for funding basic biology research,
funded a total of 29 grants totalling £5 million starting
in 1998. Many of the groups mentioned in Section 4.3
were funded by this initiative despite never having
been funded to work on aging previously, so by that
measure it is the main cause of the surge in biogerontology research in the UK.
6. Future prospects
The conspicuous success of the SAGE initiative has
led at once to the BBSRC organizing a follow-up,
Experimental Research on Ageing (ERA). Applications for this new initiative, which like SAGE will
disburse up to £5 million over three years, closed in
May 2001; it is rumored to have been ®vefold oversubscribed. Thus, we can look forward with
con®dence to a continuation of the remarkable
volume of high-quality research into aging that is
presently undertaken in the UK.
A further measure of the UK's success in this area
is the relatively small number of UK researchers who
have recently moved abroad: only two major recent
emigrants are known to the present author. This
virtual absence of a `brain drain' is a vital requirement
for the long-term health of any area of research, so we
must hope Ð and can expect Ð that it will continue.
The only note of caution that must be raised is with
regard to the confusion presently widespread in the

A.D.N.J. de Grey / Experimental Gerontology 37 (2001) 1±7

UK concerning what research on aging is intended, or
likely, to achieve in the medium and long term.
Descriptions or `mission statements' published by
the funding bodies described above include the
following:
ªThe aim of ERA is to understand the basic biology
of healthy aging. It is hoped that such information
could eventually lead to new treatments that could
reduce age related decline and thus increase `healthspan' and improve quality of life for the elderly. ERA
is not aimed at lengthening life span or addressing
speci®c age related diseases such as Alzheimer's.º
(BBSRC, 2001).
ªBoth life expectancy and healthy life expectancy
increased between 1981 and 1995; but healthy life
expectancy Ð the number of expected years of life
in good or fairly good general health Ð did not
increase by as much as life expectancy. This means
that both men and women are living more years in
poor health or with a limiting long-standing illness.
Research into Ageing is committed to funding
research that will help to close this gap: to achieve a
healthspan to ®t our lifespans.º (Research into
Ageing, 2000).
By these words, the UK's major funders of biogerontology research are committing themselves to
contribute to the continuation of the trend termed
`compression of morbidity' (Fries, 1980) Ð the
increase of healthspan but not (or, at least, to a lesser
degree) lifespan. Noble though this aspiration may be,
it is increasingly clear that nothing of the kind will
result from our research, simply because medicine
that works on robust people (postponing their frailty)
tends also to work on frail people (postponing their
death). Healthspan is much harder to measure than
lifespan, whose `rectangularization' is now ®rmly
established to have ceased in the western world
about 50 years ago (Wilmoth and Horiuchi, 1999),
but the evidence that there is also no ongoing
compression of morbidity is likewise now solid
(Research into Ageing, 2000; Crimmins, 2001).
Thus, the mission statements quoted above are almost
certain to be unful®lled; since it is the public's money
that such bodies are spending, this seems decidedly
unsatisfactory (at least to the present author). Moreover, it is wholly unnecessary: the failure of morbidity
to be further compressed is due not only to the
availability of medicine that prolongs frailty but to

5

its take-up by frail individuals, who thereby demonstrate that they predominantly prefer frailty to death.
Thus, biogerontologists should regard undiminished
(or even marginally extended) morbidity not as a
failure, or even as the price we have to pay for
substantially increased healthspan, but as a bonus.
The present tendency to justify funding of biogerontology research on the basis that it will further
compress morbidity is not only misleading but also
illogical. It should be discontinued before its inconsistency comes to the attention of policy-makers and
the general public.
References
Aspinall, R., Andrew, D., 2000. Thymic atrophy in the mouse is a
soluble problem of the thymic environment. Vaccine 18, 1629±
1637.
Banerjee, M., Sanderson, J.D., Spencer, J., Dunn-Walters, D.K.,
2000. Immunohistochemical analysis of ageing human B and
T cell populations reveals an age-related decline of CD8 T cells
in spleen but not gut-associated lymphoid tissue (GALT). Mech.
Ageing Dev. 115, 85±99.
BBSRC, 2001. BBSRC Online Consultations: Experimental
Research into Ageing. http://www.bbsrc.ac.uk/society/consult/
era/Welcome.html
Beatty, S., Murray, I.J., Henson, D.B., Carden, D., Koh, H., Boulton, M.E., 2001. Macular pigment and risk for age-related macular degeneration in subjects from a Northern European
population. Invest. Ophthalmol. Vis. Sci. 42, 439±446.
Beneke, S., Alvarez-Gonzalez, R., Burkle, A., 2000. Comparative
characterisation of poly(ADP-ribose) polymerase-1 from two
mammalian species with different life span. Exp. Gerontol.
35, 989±1002.
Boyett, M.R., Honjo, H., Kodama, I., 2000. The sinoatrial node, a
heterogeneous pacemaker structure. Cardiovasc. Res. 47, 658±
687.
Brand, M.D., 2000. Uncoupling to survive? The role of mitochondrial inef®ciency in ageing. Exp. Gerontol. 35, 811±820.
Bridger, J.M., Boyle, S., Kill, I.R., Bickmore, W.A., 2000. Remodelling of nuclear architecture in quiescent and senescent
human ®broblasts. Curr. Biol. 10, 149±152.
Burton, T.J., Elneil, S., Nelson, C.P., Ferguson, D.R., 2000. Activation of epithelial Na(1) channel activity in the rabbit urinary
bladder by cAMP. Eur. J. Pharmacol. 404, 273±280.
Butcher, S., Chahel, H., Lord, J.M., 2000. Review article: ageing
and the neutrophil: no appetite for killing?. Immunology 100,
411±416.
Charlesworth, B., 1993. Evolutionary mechanisms of senescence.
Genetica 91, 11±19.
Clancy, D.J., Gems, D., Harshman, L.G., Oldham, S., Stocker, H.,
Hafen, E., Leevers, S.J., Partridge, L., 2001. Extension of lifespan by loss of CHICO, a Drosophila insulin receptor substrate
protein. Science 292, 104±106.

6

A.D.N.J. de Grey / Experimental Gerontology 37 (2001) 1±7

Cottrell, D.A., Blakely, E.L., Johnson, M.A., Ince, P.G., Borthwick,
G.M., Turnbull, D.M., 2001. Cytochrome c oxidase de®cient
cells accumulate in the hippocampus and choroid plexus with
age. Neurobiol. Aging 22, 265±272.
Crimmins, E.M., 2001. Mortality and health in human life spans.
Exp. Gerontol. 36, 885±897.
Dean, G., Young, D.A., Edwards, D.R., Clark, I.M., 2000. The
human tissue inhibitor of metalloproteinases (TIMP)-1 gene
contains repressive elements within the promoter and intron 1.
J. Biol. Chem. 275, 32664±32671.
de Grey, A.D.N.J., Ames, B.N., Andersen, J.K., Bartke, A.,
Campisi, J., Heward, C.B., McCarter, R.J.M., Stock, G., 2001.
Time to talk SENS: critiquing the immutability of human aging.
Ann. N. Y. Acad. Sci. in press.
Durkacz, B.W., Omidiji, O., Gray, D.A., Shall, S., 1980. (ADPribose)n participates in DNA excision repair. Nature 283,
593±596.
Fotheringham, A.P., Davies, C.A., Davies, I., 2000. Oedema and
glial cell involvement in the aged mouse brain after permanent
focal ischaemia. Neuropathol. Appl. Neurobiol. 26, 412±423.
Fries, J.F., 1980. Aging, natural death, and the compression of
morbidity. N. Engl. J. Med. 303, 130±135.
Gavazzi, I., Railton, K.L., Ong, E., Cowen, T., 2001. Responsiveness of sympathetic and sensory iridial nerves to NGF treatment
in young and aged rats. Neurobiol. Aging 22, 287±296.
Gems, D., Riddle, D.L., 2000. Genetic, behavioral and environmental determinants of male longevity in Caenorhabditis elegans.
Genetics 154, 1597±1610.
Grierson, I., Unger, W., Webster, L., Hogg, P., 2000. Repair in the
rabbit out¯ow system. Eye 14, 492±502.
Hamilton, W.D., 1966. The moulding of senescence by natural
selection. J. Theor. Biol. 12, 12±45.
Harris, N., MacLean, M., Hatzianthis, K., Panaretou, B., Piper,
P.W., 2001. Increasing Saccharomyces cerevisiae stress resistance, through the overactivation of the heat shock response
resulting from defects in the Hsp90 chaperone, does not extend
replicative life span but can be associated with slower chronological ageing of nondividing cells. Mol. Genet. Genomics 265,
258±263.
Hinks, G.L., Franklin, R.J., 2000. Delayed changes in growth factor
gene expression during slow remyelination in the CNS of aged
rats. Mol. Cell. Neurosci. 16, 542±556.
Hipkiss, A.R., Brownson, C., Carrier, M.J., 2001. Carnosine, the
anti-ageing, anti-oxidant dipeptide, may react with carbonyl
groups. Mech. Ageing Dev. 122, 1431±1445.
Hyland, P., Barnett, C., Pawelec, G., Barnett, Y., 2001. Age-related
accumulation of oxidative DNA damage and alterations in
levels of p16(INK4a/CDKN2a), p21(WAF1/CIP1/SDI1) and
p27(KIP1) in human CD4 1 T cell clones in vitro. Mech.
Ageing Dev. 122, 1151±1167.
James, S.E., Faragher, R.G.A., Burke, J.F., Shall, S., Mayne, L.V.,
2000. Werner's syndrome T lymphocytes display a normal in
vitro life-span. Mech. Ageing Dev. 121, 139±149.
Karatza, C., Stein, W.D., Shall, S., 1984. Kinetics of in vitro ageing
of mouse embryo ®broblasts. J. Cell Sci. 65, 163±175.
Kirkwood, T.B.L., Holliday, R., 1979. The evolution of ageing and
longevity. Proc. R. Soc. Lond. B, Biol. Sci. 205, 531±546.

Lambert, A.J., Merry, B.J., 2000. Use of primary cultures of rat
hepatocytes for the study of ageing and caloric restriction.
Exp. Gerontol. 35, 583±594.
Lavery, W.L., Goyns, M.H., 2001. Decline in expression of TNFalpha, TACE and C4BP genes may contribute to impairment of
the immune response with increasing age. Mech. Ageing Dev.
122, 1351±1352 (abstract).
Mankouri, H.W., Morgan, A., 2001. The DNA helicase activity of
yeast Sgs1p is essential for normal lifespan but not for resistance
to topoisomerase inhibitors. Mech. Ageing Dev. 122, 1107±
1120.
Martin, K., Potten, C.S., Roberts, S.A., Kirkwood, T.B.L., 1998.
Altered stem cell regeneration in irradiated intestinal crypts of
senescent mice. J. Cell Sci. 111, 2297±2303.
McArdle, A., Pattwell, D., Vasilaki, A., Grif®ths, R.D., Jackson,
M.J., 2001. Contractile activity-induced oxidative stress: cellular origin and adaptive responses. Am. J. Physiol. Cell Physiol.
280, C621±C627.
Medawar, P.B., 1952. An Unsolved Problem in Biology. H.K.
Lewis, London.
Ongkeko, W.M., Wang, X.Q., Siu, W.Y., Lau, A.W., Yamashita,
K., Harris, A.L., Cox, L.S., Poon, R.Y., 1999. MDM2 and
MDMX bind and stabilize the p53-related protein p73. Curr.
Biol. 9, 829±832.
Partridge, L., Barton, N.H., 1993. Optimality, mutation and the
evolution of ageing. Nature 362, 305±311.
Plunkett, F.J., Soares, M.V., Annels, N., Hislop, A., Ivory, K.,
Lowdell, M., Salmon, M., Rickinson, A., Akbar, A.N., 2001.
The ¯ow cytometric analysis of telomere length in antigenspeci®c CD8 1 T cells during acute Epstein-Barr virus infection. Blood 97, 700±707.
Powell, C.D., van Zandycke, S.M., Quain, D.E., Smart, K.A., 2000.
Replicative ageing and senescence in Saccharomyces cerevisiae
and the impact on brewing fermentations. Microbiology 146,
1023±1034.
Research into Ageing, 2000. Research into Ageing Annual
Review±1999/2000. http://www.ageing.org/news/RIA_Report_
2000.pdf
Rodriguez-Lopez, A.M., Jackson, D.A., Nehlin, J.O., Iborra, F.,
Warren, A.V., Cox, L.S., 2001. DNA replication fork co-ordination is defective in Werner's syndrome: a model for normal
human ageing?. Mech. Ageing Dev. 122, 1356±1357 (abstract).
Selman, C., Lumsden, S., Bunger, L., Hill, W.G., Speakman, J.R.,
2001. Resting metabolic rate and morphology in mice (Mus
musculus) selected for high and low food intake. J. Exp. Biol.
204, 777±784.
Sgro, C.M., Partridge, L., 1999. A delayed wave of death from
reproduction in Drosophila. Science 286, 2521±2524.
Singleton, A.B., Gibson, A.M., McKeith, I.G., Ballard, C.G.,
Edwardson, J.A., Morris, C.M., 2001. Nitric oxide synthase
gene polymorphisms in Alzheimer's disease and dementia
with Lewy bodies. Neurosci. Lett. 303, 33±36.
Smith, J., Goldsmith, C., Ward, A., LeDieu, R., 2000. IGF-II
ameliorates the dystrophic phenotype and coordinately downregulates programmed cell death. Cell Death Differ. 7, 1109±
1118.
Teo, S.H., Jackson, S.P., 2001. Telomerase subunit overexpression

A.D.N.J. de Grey / Experimental Gerontology 37 (2001) 1±7
suppresses telomere-speci®c checkpoint activation in the yeast
yku80 mutant. EMBO Rep. 2, 197±202.
Williams, G.C., 1957. Pleiotropy, natural selection and the evolution of senescence. Evolution, 398±411.
Wilmoth, J.R., Horiuchi, S., 1999. Rectangularization revisited:
variability of age at death within human populations. Demography 36, 475±495.

7

Wyllie, F.S., Jones, C.J., Skinner, J.W., Haughton, M.F., Wallis, C.,
Wynford-Thomas, D., Faragher, R.G.A., Kipling, D., 2000.
Telomerase prevents the accelerated cell ageing of Werner
syndrome ®broblasts. Nat. Genet. 24, 16±17.
von Zglinicki, T., Pilger, R., Sitte, N., 2000. Accumulation of
single-strand breaks is the major cause of telomere shortening
in human ®broblasts. Free Radic. Biol. Med. 28, 64±74.