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UNIVERSITY OF PADUA ITALY
European Master in Gerontology Programme
Introductory Module 2006 THE AGES OF MAN What
Natural History Can Tell Us About Ageing

Prof. Andrea G. Drusini, M.D.
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Name Andrea G. Drusini Date of Birth July 13,
1947 Nationality Italian Marital Status
celibate Education M.D., Associate Professor of
Anthropology Institution University of Padua,
Italy Hobbies books, music, writing, travelling
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Nature is not God A hypothesis is not a fact Man
is not a machine (Denis Diderot) As other
natures sciences, biology today has lost many
illusions. Biology does not look at the truth,
rather it builds it. (Ernst Mayr)
Denis Diderot (1713-1784)
Thinking in a biological perspective
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CRITICS TO REDUCTIONISM "Extreme analytical
reductionism is a failure because it cannot give
proper weight to the interaction of components of
a complex system. An isolated component almost
invariably has characteristics that are different
from those of the same component when it is part
of its ensemble, and does not reveal, when
isolated, its contribution to the interactions"
Ernst Mayr Mayr E., 1982a, The Growth of
Biological thought. Diversity, Evolution, and
Inheritance. The Belknap Press of Harvard
University Press, Cambridge, Mass., London,
England, p. 61.
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Great Things About Getting Older

• THE ALTERNATIVE IS WORSE...

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The basic biological processes (Ernst Mayr,
1982b) Teleological Processes All things are
directed toward an end and the intelligence that
govern them is God Teleomatic Processes They
depend on the natural laws the gravity, for
example, is a necessity. All these processes
reach their end when their potential is consumed
radioactive degradation and in living organisms
the metabolic processes, the blood circulation
and the immunitary response. Teleonomic
Processes Are based on the principle "nothing do
exist in nature who is not direct to a target "
(Mayr uses the term target, different from
purpose who implies a finality). The best example
is the fecundation and eggs development. All
these processes are under the control of a
program (reproduction, mating, etc.)
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THE ORIGINS OF LIFE
In 1953, Stanley L. Miller, at the Chicago
University, reproduced with some laboratory
instruments the conditions of the prehistoric
Earth environment. Into a series of tubes and
coils, Miller simulated what he supposed to be
the Earth atmosphere of 4 billions years ago
then, he bombarded such atmosphere with
electric discharges, simulating thunderbolt, and
a spontaneous synthesis of some amino-acids
organic compounds which may be regarded as the
fundamental constituents of living matter
suddenly appeared
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THE STANLEY MILLER REACTION APPARATUS (1953)
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Alanine
Alanine 3D Molecular Model
Amino-acids are organic compounds which contain
at least one amino group and one acidic group,
regarded as the fundamental constituents of
proteins
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It was not really alarming at firstbut I did
notice that my surroundings took on a different
tone at certain times the shadows of nightfall
seemed more somber, my mornings were less
buoyant, walks in the woods became less zestful
Yet trouble came Job
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EDWARD MUNCH SCREAM 1893 Oslo, Nasjonalgalleriet
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With cell, Biology discovered its atom (F.
Jacob)
Robert Hooke was a brilliant British experimental
and theoretical scientist who lived and worked in
London during the seventeenth century. In 1665
Robert Hooke coined the term cell.
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• General types of cellular construction
• EUKARYOTIC
• Complex organization
• Internal compartments
• Organelles
• Several chromosomes within a nucleus
• Tiny
• Plants, animals, fungi, protists
• PROKARYOTIC
• Simple in organization
• No
• - compartmentalization
• Organelles
• One chromosome within cytoplasm
• Tinier
• Bacteria, algae

CELL AS AN ISLAND
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DNA The genetic code
Any cell of our body contains a blueprint 60
millions of billions of cells 60 millions of
billions of blueprints
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With death we enter the game again (Paul
Valéry)
COLEOPTERA 40 years
FLY 1 month
THE ANIMAL LIFE-SPAN
DOG 10 years
TESTUDO 150 years
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Sponges are multicellular organisms that can
reproduce themselves
The sorcerer apprentice
Dendrilla rosea
These organisms do not age at all
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The Dictyostelium discoideum world
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More simple, more long-lived?
A transmission electron micrograph of Escherichia
coli (E.coli), negatively stained to enhance
contrast. Note the projecting pili, which may be
involved in mechanisms of infection.
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The simpler the organism, the more difficult it
is to speak of ageing and death
Wayson stain of Yersinia pestis. Note the
characteristic "safety pin" appearance of the
bacteria

The pestilence, or great mortality, as it was
also called, influenced art during the period. As
expected, most artwork of the time dealt with
death and the plague. The painting shown here is
on the city of Marseilles, devastated by an
outbreak of plague
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The Measles virus
Atomic resolution in mica
Viruses can remain quiescent for thousands of
years
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Octopus
..have sex, and eventually die..
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TRICONYMPHA (Zoomastigophora)
mors tua, mors mea
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Mitochondria are the cells' power sources. They
are distinct organelles with two membranes.
Usually they are rod-shaped, however they can be
round. The outer membrane limits the organelle.
The inner membrane is thrown into folds or
shelves that project inward. These are called
"cristae mitochondriales". This electron
micrograph taken from Fawcett, A Textbook of
Histology, Chapman and Hall, 12th edition, 1994,
shows the organization of the two membranes.
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THE AGEING CHARACTERISTICS
- ageing is deleterious it reduces the
functional capacity of an organism - ageing is
progressive it goes on gradually - ageing is
intrinsic it does not depend exclusively by
environmental factors - ageing is universal it
involves all the living organisms.
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THE AGEING RESEARCH PIONEERS
The Francis Galton ageing statistics based on
God save the Queen was quoted first by Medawar
Peter Brian Medawar Nobel Prize in Physiology
or Medicine 1960
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THEORIES ON AGEING A REVIEW
The speed of life hypotesis (Pearl 1928) The
free radicals theory (Harmon 1956) The DNA
damage hypotesis (Szilard 1959) The
catastrophic error hypothesis (Orgel 1963)
The cells finite number of cycles theory
(Hayflick (1965) The glucocorticoids
hypothesis (Sapolsky, Krey and McEwan 1986) The
glyicosilation theory (Monnier 1990) The
telomere loss theory ( Lindsey and coll. 1991)

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A study in the Journal of the National Cancer
Institute showed an association between telomere
length and cancer development. The impact of
genetic and environmental factors on telomere
length is unknown.
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ANTAGONISTIC PLEIOTROPY
In the 50s, Williams (1957) introduced the
concept of antagonistic pleiotropy. Pleiotropy
is a biological term indicating the multiple
effects of a single gene on several components of
the phenotype (p?e??? to increase ??ep? to
turn)
As Mayr stated, no gene has a constant fitness
value, because the very same gene will manifest
itself differently, depending on the complex of
other genes in which it finds itself
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THE DISPOSABLE SOMA THEORY
Tom Kirkwood - a major figure in the field of
ageing evolution - in 1998 developed what is
currently known as the Disposable Soma Theory
(DST)
DST is in analogy to the industrial habit to
invest very little on the endurance of objects
that are destined to a limited time use
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PALE
DARK
NATURAL SELECTION AT WORK the moth Biston
betularia
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Microcebus murinus
Macaca mulatta
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Rockfish (Sebastes aleutianus)
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Why after some years cars go out of use?
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DAPHNIA This animal may be more common than ants
and it probably lives in your neighborhood. It's
a fascinating animal, and you can even view its
heart beating inside the body
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HUNTINGTONS DISEASE
The CT scan is of a patient with advanced
Huntington disease. Note the diffuse cortical
atrophy and the selective atrophy of the caudate
nuclei as shown by the excessive width of the
lateral ventricles.
Chorea from the greek khoreutes, a dancer in the
choir (from which the term choreography was
derived)
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Welcome to the Absent-Mind Scientists Lab
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PROGERIA (WERNERS SYNDROME) Pathogenesis
unknown linked to deficits in cellular helicase
function Locus short arm of chromosome 8
(p21-p12)
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DROSOPHILAND
Teen-ager
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THE BIONIC DROSOPHILA
Catalase and superoxide dismutase are two enzymes
that destroy ROS (Reactive Oxygen Species). If
these enzymes are inserted into embryonic fruit
flies, their life span was extended 33 when
compared to controls.
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The Extraordinary deeds of Caenorhabditis elegans
NEMATODA (ROUNDWORMS)
Caenorhabditis elegans is a small (about 1 mm
long) soil nematode found in temperate regions,
used worldwide for genetic ageing experiments
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sheep tales
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PAPUA NEW GUINEA
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PAPUA NEW GUINEA MAN
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IN THE WAKE OF ODYSSEUSA Mythological Journey
" at any rate, that some of them put the Sirens
on Cape Pelorias Cape Faro, Sicily, while
others put them more than two thousand stadia
distant on the Sirenussae, which is the name
given to a three-peaked rock that seperates the
Gulf of Cumae Bay of Naples from the Gulf of
Peseidonia Gulf of Salerno..
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The most dangerous moment comes with victory
Napoleon IEmperor of the French 1769 - 1821
Was his death programmed?
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The two fundamental ageing
theories
(Medina, 1997) Errors storage (wear and
tear) as cells age, they accumulate errors (the
ravages of environment). Ageing is simply the
incapacity to repair such ravages  Activation of
a genetic programme (the molecular clock of age)
presence of suicide genes" which favourish the
cellular death through the apoptosis (programmed
ageing / programmed death)
APOPTOSIS the programmed cell death
Napoleon Bonaparte 1769-1821
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A telomere is a region on the very tip of
chromosomes. They are composed of a repeating
series of six nucleotides (TTAGGG). A typical
human telomere may have more than 15000 such
repeats in it. Their relevance to the ageing
process is being investigated. (Source Medina,
1997, p. 276, with permission of the Editor)
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CELL CULTURE
A Petri dish
Human cells, placed in a Petri dish, can survive
outside the body After a while cells refuse to
duplicate themselves Such microscopic menopause
is called replicative senescence
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CELL CULTURE A FIBROBLAST
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THE HAYFLICK LIMIT
Leonard Hayflick is Professor of Anatomy at the
University of California, San Francisco, School
of Medicine
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The Kebaras cave site Neanderthal skeleton
(Mount Carmel, Israel Middle-Upper Palaeolithic
transition)
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The life and death genes
Senstatin proteins. Can reverse the ageing
process in the cells of skin, brain and some
blood vessels. Some BioTech Companies try to
inhibit the skin ageing and delay
ageing. Mortality 1 (M1) and Mortality 2 (M2)
gene programs. Such genes work in tandem. They
can cause cancer (retinoblastoma gene and p53).
M1 originates the ageing process and M2 finish to
kill the cell. Longevity assurance genes (LAG
genes). These genes were studied in yeast and
man. They can extend the yeast cells life of a
30. Miscellanea. Genes wich press the trigger
of ageing in man can be found in chromosomes 1
and 4 and in other sites. Among them there are
the Werner Syndrome genes. Heat-shock genes. A
response of genes to stress.
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Menopause is a many-faceted event Following the
disposable soma theory of Tom Kirkwood, woman
is genetically programmed to live longer than
man. Women pay their long life with menopause
men instead pay their continuous reproductive
capacity with a shorter life.
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KILLER WHALE (Orcinus orca)
LIFE SPAN Male 50-60 years Female 90
years Female undergo menopause
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Longevity of the Doges in the XVI century Venice
  Leonardo Loredan (1436-1521) 1501-1520 ?
65-85 Antonio Grimani (1434-1523) 1521-1523 ?
87-89 Andrea Gritti (1455-1538) 1523-1538 ?
68-83 Pietro Lando (1462-1545) 1539-1545 ?
77-83 Francesco Donà (1468-1553) 1545-1553 ?
77-85 Marcantonio Trevisan (1475-1554)
1553-1554 ? 78-79 Francesco Venier (1489-1556)
1554-1556 ? 65-67 Lorenzo Priuli (1489-1559)
1556-1559 ? 67-70 Girolamo Priuli (1486-1567)
1559-1567 ? 73-81 Pietro Loredan (1482-1570)
1567-1570 ? 85-88 Alvise I Mocenigo (1507-1577)
1570-1577 ? 63-70 Sebastiano Venier
(1496-1578) 1577-1578 ? 81-82 Nicolò da Ponte
(1491-1585) 1578-1585 ? 87-94 Pasquale Cicogna
(1509-1595) 1585-1595 ? 76-86 Marino Grimani
(1538-1605) 1595-1506 ? 63-73 Mean age at
election 74 Mean age at death 81 Mean
duration of the 15 Doges 6.66 years
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THE EXPENSIVE TISSUE HYPOTHESIS
log10E 0.76log10P 1.77,  E brain mass
(mg) P body mass (g) Modern humans have an
encephalization quotient ratio of observed to
expected brain size EQ of 4.6 while other
primates average 1.9 0.6. This means that the
average human has a brain that is 4.6 times the
size expected for the average mammal and the
average non-human primate anthropoid has a brain
almost twice as large as that of the average
mammal.
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Neural aspects of ageing (Dani, 1998)

• Increasing brain size
• Increasing brains demands
• Nutrient restriction to the rest of the body

• Encephalization
• Neoteny
• Increased longevity

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Neural aspects of ageing (Dani, 1998)

• Retardation of growth and maturation
• Increased life span
• Nutrient surplus in modern societies

• Break of brain-metabolic adaptations
• Onset of age-related conditions (diabetes
  mellitus, Alzheimers disease)

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Ageing and the conquests of modern medicine

• According to the data by Olshansky1 if we
  consider the two major causes of death cancer
  and heart disease we shall notice how
• ? could cancer be defeated overnight, then the
  average age of the population would only increase
  by 2 years
•   ? by eliminating all heart disease the same
  would increase only by 3-4 years2
• 1 Olshansky S.J., Carnes B.A., 2001, Prospects
  for human longevity. Science 291 1491-1492.
• 2 Olshansky S.J., 1998, On the Biodemography of
  Aging A Review Essay. Population and Development
  Review 24(2) 381-393.

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WORLD RECORDS 10.000 m MEN

• First under 31 min 3058.8 Jean Bouin FRA
• 1911
• First under 30 min 2952.6 Taisto Mäki FIN 1939
• First under 29 min 2854.2 Emil Zátopek TCH 1954
  
• First under 28 min 2739.4 Ron Clarke AUS 1965
• First under 27 min 2658.38 Yobes Ondieki KEN
  1993

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World Records 10.000 m Men Linear Regression
Method with Projections Calculated on Real Times
from 1911 to 1993 (r 0.90)
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AGEINGhow do we manage theuncertainty?
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The Anchyses ProjectMultidisciplinary Research
on AgeingAnywhere something lives, there is,
open in some place, a register in which time is
inscribed (Henri Bergson)
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Great Things About Getting Older

• You can stop upgrading your software

The End