Journal of Pathology

J Pathol 2007; 211: 111–113

Published online in Wiley InterScience
(www.interscience.wiley.com) DOI: 10.1002/path.2122

Introductory Article

The pathology of ageing: concepts and mechanisms

JE Martin* and MT Sheaff
Pathology Group, Institute of Cell and Molecular Sciences, St Bartholomew’s and the London Hospital School of Medicine and Dentistry, London, UK

*Correspondence to: Abstract

JE Martin, Pathology Group,
Institute of Cell and Molecular
Sciences, St Bartholomew’s and
the London Hospital School of
Medicine and Dentistry,
Pathology and Pharmacy
Building, 80 Newark Street,
Whitechapel, London E1
1BB, UK.
E-mail: j.e.martin@qmul.ac.uk
No conflicts of interest were
declared.
The rising numbers and proportion of aged individuals in the population is a global
demographic trend. The diseases associated with ageing are becoming more prevalent, and
the associated healthcare costs are having a significant economic impact in all countries. With
these changes have come great advances in our understanding of the mechanisms of ageing.
The mechanisms of cellular ageing at a genetic, protein and organelle level are becoming
clearer, as are some of the more complex associations between environment and ageing.
System ageing is also becoming better understood, and the potential biological advantages
of ageing are being explored. Many of the advances in these fields are opening up the
prospect of targeted therapeutic intervention for ageing and age related disease.
Copyright  2007 Pathological Society of Great Britain and Ireland. Published by John
Wiley & Sons, Ltd.
Keywords: ageing; pathology; population; mechanisms; therapy

“Age doesn’t matter unless you’re a cheese.” aged 65 and over will increase as the large numbers of
people born after the Second World War and during the
Putting together some of the current thinking on age- 1960s baby boom become older’. This demographic
ing has been a great experience and challenge. This shift is occurring in many developed nations. In 2004
review issue of the Journal of Pathology addresses there were 36.3 million people over 65 in the USA,
both cellular and systems-based aspects of the ageing representing 12.4% of the population. This is expected
organism. Ageing — perhaps counter-intuitively — is to grow to 20% of the population by 2030 [4].
moving ahead more rapidly than many research areas. The global picture is similar. Key statements from
New ideas, new ways of thinking about biological the United Nations overview on ageing [5] include:
processes and new approaches abound [1]. The con-
cept that our inbuilt biodegradability has a useful • One of every 10 persons is now 60 years or older,
purpose — to stop us developing tumours — may be rising to 1 in 5 by 2050 and 1 in 3 by 2150.
of little comfort when considering an imminent knee • The oldest old (80 years or older) is the fastest
replacement [2], but scientifically it is actually a whole growing segment of the older population at 11%
new area of exploration that has promising therapeutic of the 60+ age group, rising to 19% by 2050. The
potential.
As we age, we will not be alone. The population
demographics of most Western countries are changing
rapidly. The proportion of older individuals is rising
steadily, due to falling birth rates and declining
mortality. Most of us can expect to be around to
support and embarrass our children for a lot longer
than our grandparents did to our parents. As an
example, in the UK, along with an 8% growth in
overall population, the proportion of young people
has dropped from 25% in 1971 to 19% in 2005;
16% of the UK population are now 65 or older
(compared with 13% in 1971), with the percentage
of those aged 85 and over rising from 7% in 1971 to
12% in 2005 [3] (Figure 1). Numerically, 1.2 million
of the 60.1 million UK population are aged 85 or
older. The prediction of UK National Statistics is that Figure 1. The demographics of the ageing population. Source:
‘population ageing will continue during the first half National Statistics website [3]. Crown copyright material is
of this century, since the proportion of the population reproduced with the permission of the Controller of HMSO

Copyright  2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
www.pathsoc.org.uk
112
number of those aged 100 years or older is expected
to increase 15-fold to 2.2 million by 2050.
• Striking differences exist between regions. One of
five Europeans, but one of 20 Africans, is 60 years
or older.
• Ageing in developing countries is more rapid than
in developed countries and there will be less time
to adapt to the consequences of population ageing.
• Global life expectancy is currently 66 years; how-
ever, in the least developed regions, men reach-
ing age 60 can expect only 14 more years of life
and women 16 more, while in the more developed
regions, life expectancy at age 60 is 18 years for
men and 22 years for women.
The global pattern of population change is matched
by growth and development in our understanding of
the processes involved in ageing. These processes are
now being found to operate at systemic levels of the
whole organism, and at cellular and genetic levels.
The ‘timing’ of cellular ageing, as measured by
telomere length, is discussed by Shay and Wright
[1]. They highlight the fascinating differences that are
currently being discovered between species. As the
genetic controls of ageing and associated metabolic
processes are becoming clearer, the interaction
between cell cycle control and senescence is explored
in the article on p53 by Papazoglu and Mills [6]. The
central role of autophagy in health and its role in age-
ing is a hot topic in biology, which is addressed by
Terman and colleagues [7].
Ageing-related quality of life depends largely on
ageing-related disease, rather than chronological
parameters. ‘Natural’ changes in the status of the
body with ageing, such as the changes associated
with the immune, cardiovascular and endocrine sys-
tems [8–14], overlap with ‘disease’ processes, such
as those seen in musculoskeletal and skin ‘wear and
tear’ [2,9], or cardiovascular disease as described by
Greenwald [10]. The interaction and stochastic effects
of disease and ageing changes are illustrated in sev-
eral systems and processes described in the follow-
ing articles, including ultraviolet exposure and skin
damage, noise damage and age-related hearing loss,
hypertension and renal function, body mass index and
musculoskeletal disease [2,9,10,15,16].
Ageing, it appears, is not just skin deep [9]. Chromo-
somal, nucleic acid, protein and other macromolecular
changes occur at the cellular level with increasing age
[7]. It is becoming clear that the pathways involved
often have features in common with disease processes,
providing insight into some of the mechanisms by
which the additive effects of pathology and ‘natu-
ral’ ageing occur (Figure 2). In particular, interactions
between nutrition, environment, disease and ageing
are beginning to be explored, throwing up intrigu-
ing ideas about the pathogenesis of major disorders
[8,10,11,15,17]. Along with the better understanding
of these fundamental processes, there is a glimmer on
J Pathol 2007; 211: 111–113 DOI: 10.1002/path
Copyright  2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
JE Martin et al.
Telomeric
length
Autophagy Genetic array
Cell age
Systemic Environmental
factors damage
Figure 2. Factors in the ageing process
the horizon of the opportunity to use targeted inter-
ventions to modify the ageing process [1,6,8,9].
Better understanding of these processes and the
capacity to intervene in them to prevent disease
is becoming a healthcare priority. The social and
healthcare-associated costs to the individual of declin-
ing function with age are readily apparent in the con-
text of both hearing loss and renal function, but with
echoes in many of the systems-based articles, includ-
ing the ageing brain [15–17]. Age-related hearing loss
occurs in about 25% of people aged 65–75 and in
70–80% of those over age 75. About 10% of all people
over 70 have significant memory problems and about
half of these are due to Alzheimer’s disease (AD). The
number of people with AD doubles each decade past
age 70. With the rise in the very elderly population,
the disease burden and its impact is considerable, not
just for patients but also for carers.
The costs of particular age-related diseases have
been well quantified. Maintaining a patient with end-
stage renal failure on renal replacement therapy cur-
rently costs approximately £20 000/patient/year for a
patient on peritoneal dialysis and £22 000/patient/year
for a patient on hospital haemodialysis [18]. The cost
of ageing-associated diseases is likely to expand dra-
matically. Jean-Phillipe Codis, in an address to the
European Federation of Pharmaceutical Industries and
Associations in Athens, 2003, stated that the percent-
age of gross domestic product (GDP) spent on health-
care is expected to rise from 6% to 9% due to ageing
alone.
Whilst there is little biological or economic cause
for complacency in this area, there is a great deal of
exciting research and discovery in the field and this
review issue brings together many of the key findings
and advances that are promising to bring some spring
back into autumn.
The pathology of ageing 113

References 10. Greenwald SE. Ageing of the conduit arteries. J Pathol

2007;211:157–172.
11. Chahal HS, Drake WM. The endocrine system and ageing. J Pathol
1. Shay JW, Wright WE. Hallmarks of telomeres in ageing research.
2007;211:173–180.
J Pathol 2007;211:114–123.
12. Sampson N, Untergasser G, Plas E, Berger P. The ageing male
2. Freemont AJ, Hoyland JA. Morphology, mechanisms and pathol-
reproductive tract. J Pathol 2007;211:206–218.
ogy of musculoskeletal ageing. J Pathol 2007;211:252–259.
13. Djahanbakhch O, Ezzati M, Zosmer A. Reproductive ageing in
3. National Statistics website: www.statistics.gov.uk.
women. J Pathol 2007;211:219–231.
4. Administration on Aging website: www.aoa.gov.
14. Walker RA, Martin CV. The aged breast. J Pathol
5. Population Division, Department of Economic and Social Affairs,
2007;211:232–240.
United Nations Secretariat, New York, USA.
15. Liu XZ, Yan D. Ageing and hearing loss. J Pathol
6. Papazoglu C, Mills AA. p53: at the crossroad between cancer and
2007;211:188–197.
ageing. J Pathol 2007;211:124–133.
16. Martin JE, Sheaff MT. Renal ageing. J Pathol 2007;211:198–205.
7. Terman A, Gustafsson B, Brunk UT. Autophagy, organelles and
17. Esiri MM. Ageing and the brain. J Pathol 2007;211:181–187.
ageing. J Pathol 2007;211:134–143.
18. www.uktransplant.org.
8. Gruver AL, Hudson LL, Sempowski GD. Immunosenescence of
ageing. J Pathol 2007;211:144–156.
9. Baumann L. Skin ageing and its treatment. J Pathol
2007;211:241–251.

J Pathol 2007; 211: 111–113 DOI: 10.1002/path

Copyright  2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.