Background

How to Treat
What is ageing?
Anti-ageing
medicine
Anti-ageing
strategies
Promoting
longevity
inside
Pull-out section www.australiandoctor.com.au
EARN CPD POINTS Complete How to Treat quizzes online (www.australiandoctor.com.au/cpd) or in every issue see page 34.
PROFESSOR
DAVIDGLECOUTEUR,
director, Centre for Education
and Research on Ageing (CERA),
University of Sydney; director,
biogerontology laboratory, ANZAC
Research Institute; and senior
staff specialist in geriatric
medicine, Concord Repatriation
General Hospital, Sydney, NSW.
The authors
ASSOCIATEPROFESSOR
ARTHUREVERITT,
visiting research fellow, CERA,
University of Sydney, NSW.
This portrait of change in the
worlds population [ageing] paral-
lels the magnitude of the industrial
revolution traditionally consid-
ered the most significant social and
economic breakthrough in the his-
tory of humankind.
1
THE Uni t ed Nat i ons predi ct s t he
ageing of the worlds population will
influencesociety to an extent that will
match or exceed the Industrial Revo-
lution as the most profound social,
health and economic breakthrough in
the history of humankind.
1
In 1900 only 10-17 million people
were aged 65 or older and they made
up less than 1% of the worlds pop-
ul at i on. By 2000 t hi s group had
increased to 606 million and almost
10% of the worlds population.
According to the UN report World
Population Prospects, t hi s group
could swell to 1.9 billion by 2050
and const i t ut e one-f i f t h of t he
worlds projected population.
2
Thefastest-growing group istheso-
called oldest old, those aged 80 and
above. In 2000, 69 mi l l i on peopl e
were in that category; by 2050 their
number could reach 377 million.
There are currently 180,000 cen-
t enar i ans wor l dwi de, a number
expected to grow to 3.2 million by
2050.
I n Aust r al i a t he aver age l i f e
expectancy i s 82 years for women
and 76 for men, yet further ageing
(an increase in the average age) of
the Australian population is unavoid-
able over the next five decades, and
some bel i eve t hat maxi mum l i f e
expectancy will also gradually grow.
Longevity
contd page29
Correction
In last weeks How to Treat
(The short child) question 3b
of the quiz should have read:
His height velocity would be
most accurately measured over
a minimum of three months.
Also, a production error saw the
last line drop off question 10d.
It should have read: Pubertal
stage/progress inconsistent
with chronological age.
Australian Doctor apologises
for these errors.
THIS ISSUE
TUNNEL VISION
Dr Frank Gorman v The Medical World
Read his story in the November issue of FOCUS, with this issue in Australian Doctor.
FOCUS
THE AUSTRALIAN DOCTOR M AGAZINE
28 October 2005 | Australian Doctor | 27 www.australiandoctor.com.au
AD_HTT_027_034___OCT28_05 25/10/05 9:43 AM Page 27
AGEI NG does not occur
because of some uni versal
cel l ul ar def ect or t o f ul f i l
laws of physics or evolution.
I f a si ngul ar, unavoi dabl e
flaw caused every cell to fail
eventually, no animal would
escape agei ng but some
do.
For exampl e, sea ane-
mones kept for decades i n
aquariums do not show fail-
ing health or increased sus-
ceptibility to disease consis-
tent with an ageing process.
And many species have neg-
l i gi bl e agei ng , i ncl udi ng
rockfi sh, sturgeon, turtl es,
bi val ves and possi bl y l ob-
sters.
Instead, old age is thought
t o be t he by-product of a
pattern of natural selection
i n sexual l y r epr oduci ng
species. In the past the force
of natural selection declined
after the start of adulthood
because death, secondary to
environmental factors such
as t rauma, st arvat i on and
infectious diseases, prevented
peopl e l i vi ng l ong enough
for evolution to act during
the ageing process.
Agei ng has been defi ned
as t he progressi ve l oss of
f unct i on accompani ed by
decr easi ng f er t i l i t y and
i ncr easi ng mor t al i t y wi t h
advancing age.
Old age is also associated
with changes in the response
to therapeutic interventions,
be t hey phar macol ogi cal ,
sur gi cal or r ehabi l i t at i ve.
These changes usually mean
reduced ef f ect i veness and
increased adverse effects.
Thi s aspect of agei ng i s
cr i t i cal f or doct or s i f
ol der peopl e responded to
t her apy as wel l as t hei r
younger counterparts, age-
rel at ed di sease woul d not
have such a great impact.
Biological ageing
Most definitions of biologi-
cal ageing now include the
following concepts:
n
Acquisition of deleterious
changes.
n
Increased susceptibility to
disease and trauma.
n
Non-l i near i ncr ease i n
chance of death.
From a cel l ul ar perspec-
tive, several mechanisms that
probably contribute to age-
related changes in adaptive
responses, i ncl udi ng phar-
macol ogi cal responses, are
consi dered to underl i e the
ageing process.
As wi t h most i ssues i n
older people, it is likely that
ageing is multifactorial and
secondary to a combination
of t he f ol l owi ng mecha-
nisms, at the cellular level.
Oxidative stress
The f ree-radi cal t heory of
ageing was first proposed by
Denman Har man i n t he
1950s. Age-related oxidative
injury in multiple tissues is
a wi despread observat i on
with ageing.
Mitochondria and ageing
Mitochondria are both pro-
ducers and targets of oxida-
tive stress. Accumulation of
somatic mutations of mito-
chondrial DNA, induced by
exposure to reactive oxygen,
leads to impaired production
of adenosi ne t ri phosphat e
(ATP).
Telomeres and cellular
senescence
I n cul t ur e, di pl oi d cel l s
under go onl y a l i mi t ed
number of cellular divisions
(cal l ed the Hayfl i ck l i mi t).
One expl anat i on f or cel l s
r eachi ng t hi s l i mi t ar i ses
f rom t el omeres, repet i t i ve
DNA sequences at the end
of linear DNA that shorten
with each cellular division.
Genetic mechanisms
The heritability of life expec-
tancy is about 20-30%. This
observation has been inter-
pr et ed t o i ndi cat e t hat
longevity is primarily related
to individual health-related
behaviours.
Although genetic variabil-
ity has been linked causally
with decreased and increased
l i fe expectancy, i n general
t he agei ng pr ocess i s not
considered to be genetically
programmed.
However, if it is assumed
that genes control all biolog-
ical functions, it is a corol-
lary that maximum life span
i s al so l i mi t ed by genes,
al t hough our chance of
reaching this potential age is
determined by environmen-
tal and random factors.
Establishing causality
There are inherent problems
with any research into inter-
vent i ons t hat i nf l uence
ageing. First, life expectancy
i n most hi gher speci es i s
l ong, renderi ng st udi es of
interventions problematic.
Second, there is no simple
bi omar ker of agei ng t hat
could act as a surrogate or
intermediate marker of the
agei ng process. Most mea-
surabl e parameters change
gradually with age.
Consequent l y i t i s a
common trap to find a cor-
rel at i on bet ween any t wo
parameters that change with
ol d age and t hen cl ai m
causal i t y because of t hi s
associ at i on (f or exampl e,
f al l s caused by vi t ami n D
def i ci ency, l ongevi t y and
telomere length, brain ageing
caused by oxidative stress).
Primary ageing versus
secondary ageing
Pr i mar y agei ng i s a t er m
used to describe the aspects
of ageing that are indepen-
dent of disease. Anti-ageing
t her api es ar e supposedl y
di r ect ed at t hese pr i mar y
ageing processes.
In theory at least, the pri-
mary ageing process deter-
mi nes t he maxi mum l i f e
span, whi ch i s the l ongest
life span that any individual
of the species might achieve
wel l over 120 years for
humans.
Secondary agei ng i s t he
consequence of the primary
ageing process and is usually
considered to be a product
of the di seases of ol d age.
Without question, ageing is
t he mai n r i sk f act or f or
almost all disease.
Improvements in lifestyle,
medi cal i nt ervent i ons and
environmental factors have
minimised the other risk fac-
tors for many diseases, and
i t has been esti mated that
from age 28 the chances of
death are largely determined
by ageing.
Although it is possibly a
semantic and artificial issue,
ageing is not considered to
be a di sease. Nevert hel ess
t he i nci dence of di sease
increases markedly with age
and this is the most relevant
fact for clinicians.
Mortality increases expo-
nentially with age and this
forms the basis of the Gom-
per t zi an sur vi val cur ve
(fi gure 3). In centenari ans
the mortality rate diminishes
somewhat , pr obabl y as a
result of survivor bias.
Age-related deterioration
in various physiological func-
ti ons (for exampl e, l oss of
muscle mass, reduced com-
pl i ance of t he vascul ar
syst em, i mpai r ed ener gy
metabolism) also impacts on
independence and disability,
regardless of concurrent dis-
ease processes.
There is no question that
an older person who isfreeof
disease (using current defini-
t i ons of di sease) does not
have the functional capacities
of a much younger person.
www.australiandoctor.com.au 28 October 2005 | Australian Doctor | 29
The Nat i onal St rat egy f or an
Ageing Australia reports that 9%
of the population was aged over 65
i n 1976. By 1998 t hi s gr oup
accounted for 12% of the popula-
tion, and the projection for 2051 is
26%.
The number of ver y el der l y
peopl e i s i ncr easi ng at an even
faster rate: i n 1997 1.2% of the
population was older than 85, and
this percentage will increase four-
fold within 50 years (see figure 1).
The l ongevi t y r evol ut i on has
added a quarter of a century to life
expectancy over the past 100 years
and the i mpact of thi s change i s
already apparent.
Yet the baby boomers the
l argest generati on i n hi story and
one-quarter of our population
will not turn 65 (on average) until
2011. Thus, al though the heal th
care system is already proclaimed
to be i n cri si s as a resul t of the
increasing demands of our ageing
population, we are only at the van-
guard of the demographic impact
of this phenomenon.
As the baby boomer generation
gr ows ol der over t he next f ew
decades, there wi l l be si gni fi cant
changes in the nature and charac-
teristics of the older population.
Thi s cohort has been the most
productiveand powerful in Western
civilisation and has benefited from
educational and health services that
were developed after World War II.
I n l at er l i f e t hey wi l l have
heightened expectations for quality
of l i fe, heal th, fi nanci al securi ty
and i nvol vement i n pol i cy deci -
sions.
Extreme longevity
supercentenarians
A supercentenarian is someone who
has reached the age of 110 or more,
something achieved by only onein a
thousand centenarians. More than
800 supercentenarianshavebeen doc-
umented i n hi story and 90% are
f emal e. The ol dest document ed
humans are Shigechiyo Izumi (120
years, 237 days), and JeanneCalment
(122 years, 164 days[seebox above]).
A list of theworlds oldest people
can be found at www.grg.org/cal-
ment.html. Theapproximatecumu-
lative numbers of historically vali-
dated supercentenarians(asof 2005)
areshown in figure2.
What is ageing?
Figure3: Gompertz survival curve. Thechanceof dying
increases exponentiallyrather thanlinearlywithage.
Figure1: Theageingof theAustralianpopulation.
Figure2: Number of supercentenarians recordedinthehistoryof humankind.
from page27
Jeanne Louise Calment the oldest
person in the history of humankind?
Jeanne Louise Calment (21 February, 1875
4 August, 1997) has the longest confirmed
lifespan of any human being in history.
Her unusually long life produced many
advantages. For example, in 1965, she
signed a deal to sell her apartment with a
reverse mortgage, where the purchaser
agreed to pay a monthly sum until she died.
She was 90 years at the time and the value of
the apartment was equivalent to 10 years
of payments. Not only did she survive for more than 30 years, but the
purchaser died first and his wife had to continue the payments.
At 110, Ms Calment moved into a nursing home. She gained international
fame when the centenary of Van Goghs visit to her hometown of Arles,
France, provided an occasion for her to meet reporters. She said that in her
younger years she met Van Gogh, who was dirty, badly dressed and
disagreeable.
By then famous, she appeared in the film Vincent and Meat age 114.
A documentary on her life, Beyond 120 Years with J eanne Calment, has
been made. In 1996, the nursing home where she lived released a CD
called Times Mistress, which featured her reminiscences, set to rap music.
Some of her famous quotes include:
n
I' ve been forgotten by a good God.
n
I' ve only got one wrinkle, and I' m sitting on it.
n
Wine, I' m in love with that.
>65yrs
>85yrs
P
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r
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t
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g
e

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p
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p
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a
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o
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r

o
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s
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p
e
r
c
e
n
t
e
n
a
r
i
a
n
s
800
600
400
200
0
1900 2000 2050
Year
110 112 114 116 118 120 122 124
Age(years)
0 10 20 30 40 50 60 70 80 90 100 110
Age(years)
P
r
o
p
o
r
t
i
o
n

o
f

d
e
a
t
h
s

0 10 20 30 40 50 60 70 80 90 100 110
Age(years)
R
e
l
a
t
i
v
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m
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a
l
i
t
y
0.04
0.03
0.02
0.01
AD_HTT_027_034___OCT28_05 25/10/05 9:43 AM Page 29
ANTI-ageing medicine is a
term used widely to describe
the promotion of strategies
to prolong life by acting on
the primary ageing process.
It is not a medical discipline
and is generally considered
t o be a pseudo-sci ent i f i c
practice consisting mostly of
unpr oven and, at t i mes,
pot ent i al l y harmf ul t hera-
pies.
It has been estimated that
i n 2002 t he ant i -agei ng
market, fuelled by Internet
si tes and l ongevi ty cl i ni cs,
was worth US$43 billion. In
the US this growing move-
ment, led by the American
Academy of Ant i -Agi ng
Medicine (A4M), has been
criticised extensively by the
established medical and sci-
entific communities.
A public hearing into anti-
ageing medicine held in the
USSenate in 2001 was enti-
tl ed Swi ndl ers, Hucksters
and Snake Oil Salesmen: the
Hype and Hope of Market-
ing Anti-Aging Products to
Seniors.
Thi s cr i t i ci sm has been
mounted for two main rea-
sons: to protect the publ i c
from unscrupul ous practi -
tioners and to protect the
credi bi l i t y of l egi t i mat e
sci ent i f i c and medi cal
r esear ch i nt o agei ng
(now called longevity
science and medicine).
I t has al so been
argued that the anti -
agei ng movement i s
generating widespread
agei sm because of i t s
underl yi ng assumpt i on
t hat agei ng i s bad and
shoul d, i f possi bl e, be
avoided.
The history of anti-ageing
medicine
Anti-ageing medicine dates
back t o t he begi nni ng of
recorded time.
The River of Immortality
was bel i eved to fl ow from
the Garden of Eden. Specific
efforts to prevent ageing and
promote longevity have been
recogni sed as f ar back as
3500BC.
I n t he 13t h cent ury t he
Franciscan friar and scholar
Roger Bacon suggested that
ageing could be retarded by
a controlled diet, proper rest
and exercise, moderation in
l i festyl e, good hygi ene and
i nhal i ng t he br eat h of a
virgin.
This last idea is thought to
be related to the story that
Ki ng Davi d sl ept bet ween
two virgins in an attempt to
rejuvenate himself.
Bacon believed that ageing
was t he unnat ur al conse-
quence of Adam and Eves
fall into sin and that a 900-
year l i f espan coul d be
achieved with alchemy.
I n t he 16t h cent ur y
Spani ar d Juan Ponce de
Leon was rewarded for his
servi ces t o hi s count ry by
being given the right to find
Bimini, one of the islands in
the Bahamas and the rum-
oured site of the Fountain of
Youth.
He organised two expedi-
tions to find this island and
i nst ead l anded i n t he
sout her n r egi ons of
what is now the US,
nami ng thi s regi on
Fl ori da because of
its numerous flow-
ers.
I n hi s second
expedition to dis-
cover the Fountain
of Yout h he was
ki l l ed at age 61,
shot wi t h ar r ows
fired by Native Amer-
icans.
I n t he 19t h cent ur y,
Charl es Brown-Sequard, a
prominent French professor
of neurophysiology, announ-
ced that at age 72 he had
reversed his own ageing by
i nj ect i ng hi msel f wi t h a
liquid extract derived from
t he t est i cl es of dogs and
guinea pigs.
He t ol d t he Societe de
Biologie in Paris that these
i nj ecti ons had i ncreased
hi s physi cal st r engt h,
intellectual energy and
the length of the arc
of his urine.
I mpl ant at i on of
testicles from young
pri soners and ani -
mals became a pop-
ul ar and l ucrat i ve
anti-ageing interven-
tion for the next few
decades. By 1928 this
so-called Stanley pro-
cedur e had been per -
f or med i n mor e t han
50,000 subjects.
The hunt for anti-ageing
r emedi es has not been
avoided by recognised scien-
tists such as those awarded
Nobel Laureates.
Russi an zool ogi st and
mi crobi ol ogi st El i e Metch-
ni koff bel i eved that agei ng
was secondary to the release
of toxins from the gut and
suggested yogurt or removal
of the large intestine as an
anti-ageing approach.
Famed bi ochemi st Li nus
Paul i ng bel i eved i n t he
powers of high-dose antioxi-
dants, specifically vitamin C.
I n t he 1960s cryogeni cs
was pr omot ed as a new
method of achieving immor-
tality. This process consisted
of snap-freezing the body or
head at the time of death in
the hope that future genera-
tions might be able to resus-
ci t at e and r ej uvenat e t he
tissue or DNA.
Sever al hundr ed peopl e
have already undergone such
snap-f reezi ng at a cost of
about US$100,000 per
freeze.
These days, cocktai l s of
hor mones (sex st er oi ds,
growth hormone, dehydro-
epi androst erone [ DHEA] ,
melatonin), vitamins, antiox-
i dant s and West ern medi -
cines (metformin, selegiline
[ El depr yl , Sel gene] ) have
been promoted extensively.
It is believed there is wide-
spread uptake of these med-
ications. Clearly the medical
danger s i nher ent i n such
approaches are considerable.
Anti-ageing pills and
potions do not work
In 2002 a consortium of 51
l eadi ng sci ent i st s l ed by
Ol shansky, Hayf l i ck and
Carnes published a position
statement in Scientific Amer-
ican about anti-ageing medi-
cine. The conclusions were
strongly worded, to say the
least. They wrote:
Since recorded history
individuals have been, and
are continuing to be, vic-
timised by promises of
extended youth or increased
longevity by using unproven
methods that allegedly slow,
stop or reverse ageing.
Our language on this
matter must be unambigu-
ous: there are no lifestyle
changes, surgical procedures,
vitamins, antioxidants, hor-
mones or techniques of
genetic engineering available
today that have been
demonstrated to influence
the processes of ageing.
We strongly urge the
general public to avoid
buying or using prod-
ucts or other interven-
tions from anyone
claiming that they will
slow, stop or reverse
ageing.
However, they were
not pessi mi sti c, noti ng
that improved health and
del ay i n onset of age-
related disease is possible at
any age through adoption of
wel l -est abl i shed l i f est yl e
modifications:
What medical science
can tell us is that because
ageing and death are not
programmed into our genes,
health and fitness can be
enhanced at any age, pri-
marily through the avoid-
ance of behaviours (such as
smoking, excessive alcohol
consumption, excessive
exposure to sun, and obe-
sity) that accelerate the
expression of age-related dis-
eases and by theadoption of
behaviours (such as exercise
and a healthy diet) that take
advantage of a physiology
that is inherently modifi-
able.
Ther e ar e medi col egal
implications associated with
the prescription and supply
of ant i -agei ng medi ci nes.
These may include:
n
Li abi l i ty rel ated to fai l ed
expectations.
n
Fraud.
n
Negligence.
n
Malpractice.
n
Warrant issues.
n
Product liability.
In Australia it is illegal to
make t her apeut i c cl ai ms
wi thout appropri ate regi s-
tration or listing by the reg-
ulatory authorities. In gen-
er al , a br each has t o be
r epor t ed bef or e act i on i s
taken.
A useful gui de that may
hel p t he GP i dent i f y and
understand the claims com-
monl y made by those pro-
moting anti-ageing therapy
was publ i shed by Par k,
2002.
3
The si gns and t r i cks of
quackery descri bed i n t he
guide include:
n
Theclaim ispitched directly
to the media without evi-
dence of unbi ased peer
review.
n
The purveyors work or
message is said to be sup-
pressed by t he sci ent i f i c
establishment.
n
Phrases such as scientific
breakthrough , excl usi ve
product, secret ingredient,
or anci ent r emedy ar e
used.
n
Testimonials and anecdotes
are pervasive.
n
Centuries-old remedies are
said to be credible because
they have wi thstood the
test of time.
n
Attempts to convey credi-
bi l i t y are made by usi ng
references or links to white
coats, MDs, academies and
institutes.
n
Claimsthat sound too good
t o be t rue are made and
t her e i s an absence of
adverse reactions.
n
Si mpl i st i c rat i onal es are
used to dupe the lay public.
n
Use of cel ebri ti es to pro-
mot e pr oduct s, and
at t empt ed associ at i ons
with well-known legitimate
scientists.
n
The esteemed medical tra-
di t i on of of f -l abel use i s
promoted.
n
Products are sold.
n
Misleading interpretations
of studies or outright false
cl ai ms t hat somet hi ng
works.
n
Use of disclaimers.
n
Promise of a money-back
guarantee.
n
We are on your side is a
common theme.
How to treat longevity
30 | Australian Doctor | 28 October 2005 www.australiandoctor.com.au
Anti-ageing medicine
Charles Brown-Sequard.
Spanishexplorer
JuanPoncedeLeon.
TheFountainof Youth.
AD_HTT_027_034___OCT28_05 25/10/05 9:44 AM Page 30
Vitamins and antioxidants
USbiochemist Casimir Funk
bel i eved that beri beri was
cured by a vital amino acid,
hence the term vitamin. The
curative effects of citrus fruit
on scurvy have been recog-
nised since Captain Cooks
days, but this was thought to
be related to a non-specific
effect of theacid on digestion.
Vitamins and minerals are
cl earl y effecti ve at treati ng
deficiency states. Oxidative
stress increases with ageing
and it has been thought, by
extrapolation, that the anti-
oxidant vitamins (vitamin C,
vitamin E and beta-carotene)
might delay ageing.
Thi s cont ent i on i s sup-
port ed by epi demi ol ogi cal
evidence linking a diet rich
in antioxidants and/or these
vi t ami ns wi t h i mpr oved
heal t h, pr obabl y t hr ough
impact on secondary ageing.
However, none has been
shown t o have consi st ent
benefit on age-related disease
or longevity when taken as
suppl ements i n a non-defi -
cient diet. Nor are there any
robust experi ments i n ani -
mals showing that any phar-
macol ogi cal ant i oxi dant
intervention influences max-
imum lifespan.
Nearl y a decade of ran-
domised controlled trials of
antioxidants in heart disease,
involving about 150,000 sub-
jects, have shown no benefit.
A recent meta-analysis of
vitamin E trials reported an
over al l mor t al i t y r at e of
11.3% in those taking sup-
pl ement s compar ed wi t h
11.1% in theplacebo group.
4
In beta-carotene trials there
was a small but statistically
significant increase in mor-
tality from 7.0% to 7.4%,
4
an effect seen especi al l y i n
smokers.
Although there is a corre-
lation between antioxidants,
B vitamins, folate, homocys-
teine and cognitive function,
Cochrane reviews conclude
B6 and folate have no effect
on cognitive function in later
life, and there is insufficient
evi dence f or ef f i cacy of
antioxidants in older people
with cognitive impairment.
Sex steroids
The recent Million Women
Study
5
and Womens Health
Ini ti ati ve tri al
6
showed no
benefit of long-term HRT.
The overall mortality rate
wasthesamein treatment and
control groups. Therewas an
excess of breast cancers and
thromboembolic disorders in
the group taking HRT and a
small reduction in rateof ver-
tebral and hip fractures and
colorectal cancers.
Although men havean age-
related decline in testosterone
levels, there is no benefit in
taking testosterone. The only
exception ismen who arevery
deficient, who show someben-
efit in bone mineral density
and musclecomposition.
Growth hormone
Growth hormone
l evel s decl i ne by
about 14% ever y
decade in adults, with a
parallel decline in the levels
of insulin-like growth factor
1 (I GF-1). Tr eat ment of
heal t hy adul t s and ol der
peopl e wi t h gr owt h hor -
mone l eads t o changes i n
body composition, in partic-
ular an increase in lean body
mass.
However, thi s change i n
body composition is associ-
ated with:
n
Glucose intolerance.
n
Hypertension.
n
Gynaecomastia.
n
Carpal tunnel syndrome.
n
Oedema.
n
A possible increased risk of
some cancers.
Pr oponent s of usi ng
growth hormone as an anti-
ageing therapy promote the
benef i t s seen i n def i ci ent
adults; however, there is no
evi dence of any benef i ci al
effect on health and longe-
vity in healthy adults.
In fact, studi es of trans-
geni c mi ce over-expressi ng
growth hormone showed a
r educed l i f e expect ancy,
while underproduction was
associated with improved life
expectancy.
The cost of growth hor-
mone injections for an indi-
vidual is tens of thousands
of dollars a year. Most pro-
ponent s of t hei r use ci t e
short-term benefits such as
increased muscle mass and a
slight decrease in the risk of
osteoporosi s, but there are
no l ong-term studi es of i ts
use in non-deficient adults.
Dehydroepiandrosterone
DHEA is widely used in the
USbut is prohibited in Aus-
t ral i a; however, i t i s mar-
keted and sold via the Inter-
net. Although all listed and
registered products in Aus-
t ral i a have qual i t y gui de-
lines, non-listed or imported
products come with no guar-
ant ee of composi t i on or
quality.
DHEA is an intermediate
hormone in the production
of mal e and f emal e sex
steroids. Levels decline with
age by about 2% a year; by
age 80 levels are about 20%
of t hose seen i n young
adul t s. However , t hese
reduced levels are not equiv-
alent to those seen in adrenal
insufficiency.
DHEA has been used i n
humans since the 1950s for
menopausal symptoms and
asthenia. Although some ini-
tial clinical trialsshowed pos-
itiveeffectson musclecompo-
si t i on and physi cal and
psychological markersof well-
being, all subsequent study
results havebeen negative.
I n common wi t h ot her
anabol i c steroi ds, DHEA i s
associated with hepatotoxi-
ci ty, i mpai red l i pi d profi l es
and a possi bl e i ncrease i n
the ri sk of hormone-rel ated
cancers.
Melatonin
Melatonin is a pineal gland
hor mone t hat has some
ant i oxi dant pr oper t i es at
hi gh concentrati ons and i s
secr et ed i n a ci r cadi an
manner. Whether production
declines with age is a contro-
versial issue.
Although melatonin appears
to havesomeeffectson insom-
nia and jetlag, there are no
dat a showi ng ef f i cacy f or
longevity or diseaseprevention
in older people.
In one study in mice, mela-
tonin increased maximum life
expectancy by 5%, but with
an i ncrease i n t he rat e of
malignancies.
7
Herbal remedies
Many herbal remedi es are
promoted for preventing and
treating the effects of ageing.
For exampl e, l ongevi t y
cl ai ms have been made for
herbs such as Ginkgo biloba.
There have been numerous
clinical trials of ginkgo and
some have shown cognitive
ef f ect s i n dement i a. More
importantly, however, they
show that ginkgo causes pro-
longed bleeding and interacts
with anticoagulants.
Ant i -agei ng t her api es
sometimes provided in tradi-
t i onal Chi nese medi ci ne
i ncl ude r ei shi mushr oom,
l yci um berry, j uj ube frui t,
Panax ginseng, f o-t i and
Gynostemma pentaphyllum.
There are no cl i ni cal t ri al
data to support theclaimsfor
most of t hese agent s, and
many pat i ent s t ake t hem
without informing their GP.
There are many reports in
the literature of complemen-
tary products being contam-
i nat ed wi t h heavy met al s
and/or Western medicines.
Gerovital H3
Gerovital H3 is a procaine-
based tabl et that was pro-
cl ai med t o be an ef f ect i ve
ant i -agei ng t herapy i n t he
1940s by Romanian Profes-
sor Ana Aslan. There are no
recent data to show i t has
any effects, nor would this
be expected on the basis of
its established pharmacology.
Western medicines
Some Internet sites on longe-
vity promote pharmaceutical
medications for the preven-
tion of ageing, including met-
f or mi n and sel egi l i ne (or
deprenyl), an MAOI used to
t r eat Par ki nson s di sease.
Statins and drugs for erectile
dysfunction are also heavily
advertised at these sites.
It is likely that some Aus-
tralian patients are accessing
such medicationsthrough the
Internet and that some do
not notify their GP of their
use of these potent drugs.
Caloric restriction
Benj ami n Fr ankl i n sagel y
stated, to lengthen thy life,
lessen thy meals .
Food restriction was first
shown t o pr ol ong l i f e 70
years ago. Overall, reducing
caloric intake by about 40%
i ncr eases maxi mum l i f e
expectancy by about 40% in
all animals tested to date.
The i ncr ease i n l i f e
expect ancy appears t o be
i ndependent of the type of
nutrients restricted but does
requi re nutri ti onal suppl e-
mentation to prevent specific
vi t ami n and mi neral def i -
ciencies.
Caloric restriction isassoci-
ated with delayed appearance
of the biochemical changes
seen i n normal agei ng and
delayed onset of diseases.
A number of people have
at t empt ed t o under t ake
caloric restriction, led by the
late Dr Roy Walford (1924-
2004), a hi ghl y respect ed
and successf ul sci ent i f i c
researcher who establ i shed
the Bi osphere experi ments
(figure 4).
There are no l ong-t erm
pr ospect i ve st udi es i n
humans: cal ori c restri cti on
of 40% has been found to
be too unpleasant to be sus-
tained by humans.
However , t wo human
st udi es i n heal t hy adul t s
have shown t hat reduci ng
intake of calories by about
20% over peri ods of t wo
years lowers blood pressure,
body fat and serum levels of
cholesterol and triglycerides,
glucose and insulin.
Sever al agent s, cal l ed
cal or i c r est r i ct i on (CR)
mimetics, attempt to achieve
the biological and metabolic
effects of caloric restriction
without the need for reduc-
ing food intake.
Mostly theseincludeagents
such as 2-deoxygl ucose,
iodoacetate and metformin,
which act on glucosemetabo-
lism. Obviously they also have
the capaci ty for si gni fi cant
sideeffects, including death.
www.australiandoctor.com.au 28 October 2005 | Australian Doctor | 31
Some commonly promoted anti-ageing strategies
Figure4: Dr RoyWalford, duringcaloric restriction(left) andafter resuminga normal diet.
AD_HTT_027_034___OCT28_05 25/10/05 9:44 AM Page 31
THE first approach in pri-
mar y car e i s t o pr omot e
st andar d pr event i ve and
medical interventions.
It has been estimated that
the elimination of the major
di seases causi ng deat h i n
developed countries (cardio-
vascular disease and cancers)
woul d ext end t he average
life span by nearly 20 years.
Thenumber of peopleaged
over 85 hasalready increased
dr amat i cal l y because of
reduction in deaths from car-
diovascular disease, cigarette-
r el at ed l ung di sease and
cancer.
At age 40 the combi ned
effect of smoking and obesity
leads to a loss of 13-14 years
of lifeexpectancy. In contrast,
the resolution of Alzheimers
disease would only add 19
days t o t he aver age l i f e
expectancy, but would havea
massive effect on health care
costs and human suffering.
Di sease pr event i on em-
braces nearly all aspects of
general practi ce, i ncl udi ng
vaccination, diseasescreening
and treatment of risk factors
for disease such as hyperten-
sion and hyperlipidaemia.
It i s i mportant to recog-
ni se that cl i ni cal tri al data
suggest the maj or effect of
many preventive strategies is
to reduce the i nci dence of
disease rather than increase
life expectancy.
In general , pri mary pre-
vention trials do not tend to
show any effect on mortality
and it is only in secondary
prevent i on t ri al s t hat any
mor t al i t y benef i t can be
seen. This may, in part, be
due to factors such as statis-
tical power and numbers of
events needed to show any
mortality benefit.
The second approach i n
primary care is to promote
what has been t er med
heal thy agei ng . Al though
heal thy agei ng i ncl udes al l
activities occurring through-
out l i fe that may ensure a
successful old age, there has
been a parti cul ar focus on
modi f yi ng behavi our al l y
influenced (rather than med-
ical) activities.
These i ncl ude smoki ng,
excess alcohol consumption,
exercise, maintaining healthy
body wei ght, di et, psycho-
logical and spiritual health
and social connectedness.
I n par t i cul ar t her e has
been increasing evidence for
the benefits of regular exer-
ci se. Ther e i s over l ap
bet ween many of t he f ea-
tures of ageing and those of
disuse: sedentary adults lose
20-40% of muscl e bul k
during life.
The cardi ovascul ar and
musculoskeletal response of
ol der peopl e to exerci se i s
very good, although limited
by the effects of age-related
reducti on i n beta receptor
densi t y on maxi mal heart
rate.
As well as promoting psy-
chol ogi cal wel l bei ng and
relieving depression, there is
a correlation between exer-
cise and longevity (positive
effect) and di seases of ol d
age (negative effect), such as
cardiovascular disease, type
2 di abet es, ost eopor osi s,
stroke, breast cancer, colon
cancer and depression.
Prospecti ve studi es have
shown exercise to have posi-
tive effects on risk factors for
cardiovascular disease, such
as l i pi d l evel s and bl ood
pressure, and randomi sed
studies have shown less car-
diovascular disease and dia-
betes and fewer falls.
The current recommenda-
tion for the prescription of
exercise is that people of all
ages should have at least 30
mi nut es of exer ci se t hat
makes you breathe harder
on most days of the week.
Bal ance exer ci ses may
have addi ti onal benefi ts i n
older people by reducing the
ri sk of fal l s. There i s al so
evi dence that wei ght-resi s-
tance training can have posi-
tive effects, such as lowering
blood pressure and decreas-
ing the risk of osteoporosis.
AT t hi s st age i t woul d be
inappropriate for a medical
practitioner to support and
promoteany anti-ageing med-
icines. GPsconfronted by any
patient involved in anti-ageing
activities, even when under
the supervision of other med-
ical practitioners, havea duty
t o i nf orm t he pat i ent t hat
these therapies are unproven
and possibly harmful.
On the other hand, most
clinicians recognise that the
pl acebo effect i s pervasi ve
(of t en exceedi ng 30%
response rates in randomised
cl i ni cal t r i al s) and many
people live in fear of ageing
and death.
From this perspective it is
easy t o be sympat het i c
towards people who believe
that a simple potent might
protect them agai nst thei r
demise and make them feel
less troubled by the human
predicament.
How to treat longevity
32 | Australian Doctor | 28 October 2005 www.australiandoctor.com.au
Lifestyle first line for longevity
A 58-YEAR-old man attends his GP
for the first time requesting growth
hormone and DHEA injections to
improve his life expectancy.
He has a family history of prema-
ture death, with both his father and
an older brother dying of acute MIs
before their 60th birthdays.
Very concerned he will die around
t he same age, t he pat i ent has
searched t he I nt ernet and f ound
many USsitespromoting a variety of
ant i -agei ng medi cat i ons. He has
already begun taking megadose vit-
amin E and vitamin C.
On examination his BMI is 29, he
has nicotine-stained fingernails and
his blood pressure is 170/95mmHg.
He i s advi sed t hat ant i -agei ng
medications are unproven, that the
use of growth hormone and DHEA
i n peopl e wi t hout def i ci ency i s
pot ent i al l y hazar dous, and t hat
DHEA is prohibited in Australia.
The benefits of stopping smoking,
exercise and minimising obesity are
discussed and issues related to his
risk factors for cardiovascular dis-
ease, such as blood pressure, smok-
ing and lipids are raised.
After this discussion the patient
appears to appreciate that address-
ing these lifestyle factors will have a
genui ne i mpact on i mprovi ng hi s
gener al heal t h and r educi ng hi s
chances of premat ure deat h and
heart disease.
He agrees to attend subsequent
vi si t s t o manage hi s smoki ng,
weight and cardiovascular risk fac-
tors.
Authors case study
Conclusion
The GPs approach to promoting longevity
The US National Institute on Aging (www.nia.nih.gov) makes the
following statements and recommendations to lay people that
incorporate many of the behavioural aspects of healthy ageing:*
No substance can extend life, but the chances of staying healthy
and living longer can be improved if you:
n
Eat a balanced diet, including five servings of fruits and
vegetables a day.
n
Exercise regularly (check with a doctor before starting an
exercise program if you have any chronic illnesses).
n
Get regular health check-ups.
n
Stop smoking (its never too late to quit).
n
Practise safety habits at home to prevent falls and fractures.
Always wear your seatbelt in a car.
n
Stay in contact with family and friends. Stay active through
work, play and community.
n
Avoid overexposure to the sun and the cold.
n
Use moderation if you drink alcohol. When you drink, let
someone else drive.
n
Keep personal and financial records in order to simplify
budgeting and investing. Plan long-term housing and
money needs.
n
Keep a positive attitude toward life. Do things that make
you happy.
*National Institute on Aging. AgePage. Life Extension:
Science Fact or Science Fiction?
www.niapublications.org/engagepages/lifeext.asp
Healthy ageing
References
1. UN Economic and Social
Council. I mplications of an
Ageing Society.
www.un.org/esa/socdev/
ageing/ageimpl.htm#top.
2. UN Department of
Economic and Social Affairs.
World Population Prospects:
The2004 Revision.
www.esa.un.org/unpp
3. Park R. Voodoo Science:
theRoad from Foolishness
to Fraud. Oxford. Oxford
University Press, 2002.
4. Dangour AD et al.
Micronutrient
supplementation in later life:
Limited evidence for benefit.
J ournal of Gerontology
2004; 59A:659-73.
5. Beral V, and the Million
Women Study collaborators.
Breast cancer and hormone
replacement therapy in the
Million Women Study.
Lancet 2003; 362:419-27.
6. Anderson GL et al.
Effects of conjugated equine
estrogen in postmenopausal
women with hysterectomy:
the Womens Health
Initiative randomized
controlled trial. J AMA
2004; 291:1701-12.
7. Anisimov VN et al.
Melatonin increases both
life span and tumor
incidence in female CBA
mice. Journal of Gerontology
2001; 56:B311-2.
Further reading
n
Anti-aging medicine: the
hype and the reality. The
J ournals of Gerontology
2004; 59A(6 & 7).
n
Flaherty JH, Morley JE.
Anti-aging. Clinics in
Geriatric Medicine. 2004;
20(2).
n
The quest to beat aging.
Scientific American 2000;
11(2).
n
The science of staying
young. Scientific American
2004; 14(3).
Online resources
n
The worlds oldest people:
www.grg.org/calment.
html
n
USNational Institute on
Aging: www.nia.nih.gov
n
Onlinepublicationson
healthy aging:
www.niapublications.org/
shopdisplayproducts.asp?id
=30& cat=Healthy+Aging
n
AgePage. LifeExtension:
ScienceFact or Science
Fiction?:
www.niapublications.org/
engagepages/lifeext.asp
Clinical trial data
suggest the major
effect of many
preventive
strategies is to
reduce the
incidence of
disease rather
than increase life
expectancy.
AD_HTT_027_034___OCT28_05 25/10/05 9:44 AM Page 32
Case study
RHONDA is a retired uni-
versity lecturer, aged 70. She
is divorced, smokes heavily
and is down to earth.
She i s somewhat bi t t er
about life and moved to the
local area to escape family
problems.
Rhonda was quite peeved
when breast cancer failed to
kill her five years ago. She
had agreed to surgical treat-
ment but di d not want
chemotherapy or follow-up.
She has had no recurrence
and remains well. She has no
other health problems and is
slim and agile.
We have had many discus-
sions about her annoyance
t hat she i s l i vi ng beyond
what she considers a useful
age. She is not interested in
what she cal l s f i l l i ng i n
ti me wi th el derl y peopl e,
and denies any interest in or
curi osi t y about t he worl d
that would encourage her to
look forward to a long life.
She did have an episode of
clinical depression two years
ago, triggered by problems
wi th her son and fi nanci al
worries. After a combination
of psychological counselling
and medi cat i on she now
feel s wel l , but consi ders i t
ridiculous for people her age
to outlive their usefulness .
Rhonda admi ts that her
whole life revolved around
work. She f eel s t hat , as a
result, now she is retired she
i s unabl e t o devel op new
hobbies or relationships that
would make the prospect of
old age appealing.
Questions for the authors
SomepeoplelikeRhonda do
becomedistressed at living
too long. Is the opposite
dilemma to the search for
longevity very common?
As wi t h most i l l nesses,
depression is more common
in older people.
This more likely reflects a
mechanistic biological effect
of ageing than a psychological
response to living too long.
Old age is also a risk factor
for chronic disease and dis-
ability, and these factors are
clearly associated with depres-
sion and despair.
In Rhonda s case, treat-
ment should be directed at
her depressive symptoms and
any underl yi ng chroni c i l l -
nesses. Any assumption that
her symptoms are an accept-
abl e cor ol l ar y of ol d age
must be rejected.
If a person has not devel-
oped strong relationships
and interconnectedness
throughout early life, can
practitionersintervenein any
useful way to encouragethis
asthey age?
Social connectednessappears
to havea strong impact on the
health of older people, influ-
encing such factors as hospi-
talisation risk for therecently
widowed.
The family is usually the
centreof thisnetwork, but the
failure of the nuclear family
to embrace older people and
t he hi gh di vor ce r at e ar e
impacting on the capacity of
family networks to support
older people.
Al though there are wel l -
established networksthrough
family, education (for exam-
ple, University of the Third
Age [U3A]), social and com-
munity groups and day cen-
tres, there is also an increase
in Internet-based interactions
t hr ough such si t es as
www.greypath.com
General questions for the
authors
Do any studies link extra
yearsof lifeto exercise, or is
theeffect of exercisemainly
on quality-of-lifeparameters?
Many studies have found
an association between vari-
ous measures of exercise and
l ongevi ty but there are no
randomised clinical studies.
General l y, moderate-fre-
quency exercise is effective
and the expected reduction
in mortality is in the order
of 20%, and t here i s al so
concomitant improvement in
quality of life.
There are no prospective
randomi sed studi es of any
intervention, including exer-
ci se, f or l ongevi t y i n
humans.
Arethebaby boomersgoing
to livelonger than thegenera-
tion after them, becauseof the
current obesity epidemic?
There is a concern that the
obesity epidemic will have a
substantial effect on mortality
rates, pri mari l y because of
the association between obe-
sity, diabetes and cardiovas-
cular disease.
Whether treatment and/or
prevent i on of obesi t y wi l l
have any i mpact on t he
longevity of baby boomers
children is a matter of specu-
lation. On the other hand, it
has been est abl i shed i n
ani mal exper i ment s t hat
caloric restriction increases
l ongevi t y, and i n humans
r educes r i sk f act or s f or
cardiovascular disease.
Mental attitudeseemsto be
themain determinant of a
happy old age. Isthereany
evidencethat it actually pro-
longslife?
There is a strong correla-
tion between the wellbeing,
happi ness, heal t h and
longevity of people who are
emot i onal l y and behav-
i our al l y compassi onat e.
Although the semantics are
complex, mental attitude is
themain determinant of hap-
piness at any age.
How to treat longevity
34 | Australian Doctor | 28 October 2005 www.australiandoctor.com.au
HOWTOTREATEditor: Dr Lynn Buglar
Co-ordinator: J ulian McAllan
Quiz: Dr Lynn Buglar
Longevity 28 October 2005
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The Wesley Hospital, Brisbane, Queensland.
1. Which TWO statements about the ageing
of the population are correct?
a) The fastest-growing segment of the
population is made up of the baby boomers
b) People aged over 65 made up about 10%
of the worlds population by 2000
c) The average life expectancy in Australia is
82 for women and 76 for men
d) The National Strategy for an Ageing
Australia estimates that, by 2051, 35% of
Australians will be aged over 65
2. Which TWO processes are characteristic
of ageing in humans?
a) A universal cellular defect leading to cell
death
b) Changes in response to therapeutic
interventions
c) A linear increase in the chance of death
d) An increased susceptibility to disease and
trauma
3. When discussing aspects of longevity with
patients, which ONE statement is correct?
a) The heritability of life expectancy is about
50-60%
b) Secondary ageing refers to the aspects of
ageing that are independent of disease
c) Anti-ageing therapies are usually directed
at the primary ageing processes
d) Primary ageing can be modified by
avoidance of behaviours that accelerate the
expression of age-related diseases
4. Britney, 24, attends for a routine Pap
smear. She has a strong family history of
CAD and smokes heavily. When she asks
whether supplementing her diet with
vitamins will protect her from heart disease
and improve her life expectancy you are
most likely to give which ONE reply?
a) Supplementary antioxidants and vitamins
improve longevity
b) Antioxidant supplements will lower
Britneys risk of CAD
c) Stopping smoking is the most important
modifiable risk factor for her
d) Beta-carotene supplements will lower her
mortality risk, especially because she
smokes
5. Grace, 57, works part time as a secretary
in a local nursing home. She is anxious to
avoid the illnesses she sees every day at
work. A friend from the US is taking DHEA
and is convinced of its benefits. Which TWO
statements about DHEA are correct?
a) DHEA can be prescribed in Australia
through compounding chemists
b) DHEA levels decline with age but not to a
level approaching that seen in adrenal
insufficiency
c) Her friends response may be due to a
placebo effect
d) Overall, studies show an increase in muscle
bulk and wellbeing in people taking DHEA
6. Grace has a BMI of 28, elevated lipid
levels and a family history of CAD. She is
keen to try DHEA and her friend has told
her of a US Internet site from which she
can order it. What information about taking
DHEA would you be most likely to give
Grace (choose TWO)?
a) Her lipid levels may be adversely
affected
b) Hepatoxicity is a potential side effect
c) US Internet supply of drugs is regulated
and safe
d) DHEA is an acceptable option as long as
it is medically supervised
7. Grace wonders if HRT would be beneficial
in her situation. Which TWO changes in her
level of risk could she expect if she used
HRT for the next five years?
a) An increase in breast cancer risk
b) A lowering of her risk of CAD
c) A lowering of her risk of osteoporosis
d) An overall mortality benefit
8. Max, 68, has always been active and is
worried about his decreasing strength. He
smokes 10 cigarettes a day. He has read that
growth hormone may help reverse muscle
loss. Which THREE side effects of growth
hormone use should Max be warned about?
a) Hirsutism
b) Glucose intolerance
c) Gynaecomastia
d) Hypertension
9. Max has a strong family history of
premature death. Which TWO actions would
be most likely to reduce his risk of the
diseases of ageing?
a) Weight-resistance training
b) Taking daily melatonin
c) Stopping smoking
d) Taking metformin
10. Max has a BMI of 23. He has read about
the effects of calorie restriction and
longevity. Which THREE effects could he
expect if he was to reduce his calorie intake
by 40%?
a) A reduction in blood pressure
b) Increase in lipid levels
c) A potential increase in life expectancy of
up to 40%
d) Vitamin and mineral deficiencies
Photocopy form Australian Doctor Education www.australiandoctor.com.au/cpd/
and fax to Reply Paid 60416 for immediate feedback
(02) 9422 2844 Chatswood DCNSW2067
CONTACTDETAILS
GPs contribution
DR ANNE PARKER
Bowral, NSW
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