Methuselah is the oldest person
whose age is mentioned in the Hebrew Bible. Methuselah was the son
of Enoch and the grandfather of Noah and tradition suggests
that he died at the age of 969 years, seven days before the beginning of
the Great Flood.
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| Methuselah |
Today, 'Methuselah', or 'as old as
Methuselah' is often used to refer to any living thing reaching great age. The
oldest living tree in the world is a White Mountains, California, bristlecone
pine (Pinus longaeva) named Methuselah, after the biblical character.
The Methuselah tree, found at
11,000 feet above sea level, is 4,838 years old and is the oldest living
non-clonal organism in the world. But even older than Methuselah (the tree)
was Prometheus. In 1964, a graduate student, was taking core samples
from a tree named Prometheus. After breaking his boring tool inside the tree,
he asked for permission from the US Forest Service to cut it
down and examine the full cross-section of the wood. Prometheus (once cut down)
turned out to be about 5,000 years old.
Silene stenophylla is a species of
flowering plant commonly called narrow-leafed campion. A frozen
specimen of the fruit was found in a (very old) squirrel's cache and the
germinated plants bore viable seeds. The fruit was dated to be over
31,800 years old.
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| The Methuselah Tree |
Microbial species have been noted to
have a type of 'extended longevity'. Credible researchers have claimed
'resuscitation' of bacterial spores to an active metabolic state, the spores
having been embedded in amber for 40 million years as well as
spores from salt deposits in New Mexico being revived after 240
million years.
One scientist was able to coax 34,000
year old salt-captured bacteria to reproduce and his results were
confirmed and duplicated at a separate independent laboratory facility.
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| Black Coral Genus Leiopathes |
There are many other long-lived
species. Specimens of the black coral genus Leiopathes are
among the oldest continuously living organisms on the planet, thought to be
over 4,265 years old. The giant barrel sponge Xestospongia
muta is known as one of the longest-lived animals, with the largest
specimens in the Caribbean estimated to be older than 2,300 years. There are
some species of sponges in the ocean near Antarctica which
are thought to be over 10,000 years old.
Certain animals have a 'biological
immortality' such as the hydrozoan species (small, predatory animals
related to jellyfish and corals) Turritopsis nutricula which is able
to cycle from a mature adult stage to an immature polyp stage and back
again with the implication that there may be no natural limit to its life
span.
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| Barrel Sponge Xestospongia Muta |
Even the larvae of carrion
beetles have been shown to be capable of undergoing 'reversed development'
when starved growing back at a later stage to the previously attained level of
maturity.
Clonal plant colonies are not
considered by all researchers to be a single organism but some of these
'colonies' are connected by (huge) single root system and all have the same
genetic make-up.
Pando is a Quaking Aspen tree
or clonal colony that has been estimated at 80,000 years old (possibly as
old as one million years, all 'members' of the 'colony' connected to
each other via a single massive underground root system.
The biology of longevity and ageing,
investigation of the role of genes has focused on the nematode (worm) Caenorhabditis
elegans (C. elegans). The genome of this species has been fully sequenced
with 97,000,000 base pair genome and has a normal life span of 2-3 weeks.
Several mutations have been identified in C. elegans which alter the
rate of ageing, with some mutants living more than five times as
long as wild-type worms.
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| Quaking Aspen Tree Clonal Colony |
Although immortality has not been
achieved, life expectancy for human beings has been greatly extended over the
past 2000 years. By the 1980's, the world average life expectancy reached 62
years but this figure varies hugely across the globe.
The average life expectancy of
a population has always been greatly affected by death rate at or around the
time of birth. Countries or eras of history where health care was poor and
infant mortality high, skewed the life 'expectancy' of that population to the
low side.
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| Caenorhabditis Elegans (C. Elegans) |
Life expectancy at birth between 50,000
and 10,000 years ago was about 33 years. Life expectancy then fell until
Medieval times (due to conflict?). For instance, in classical Greece and
Rome, this number was 28 years.
In Medieval Britain and Medieval
Islamic Caliphate (about the 10-12th centuries), life expectancy rose to
30-35 years.
In early 'modern' Britain (the
16th, 17th, and 18th centuries), life expectancy ranged from 25-40 years,
in early 20th century Britain, 31 years and in 2010, the world average
life expectancy at birth rose to 62 years.
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| Medieval Islamic Caliphate |
Often, life expectancy may increase with
age as the individual survives the higher mortality rates associated with
childhood. In Medieval Britain, for example, life expectancy at birth was 30
years. But a male member of the English aristocracy at the same period, having
survived to the age of 21, could expect to live to between 64 and 71 years old.
Before the Industrial Revolution,
death at young and middle age was common and lifespans over 70 years were rare.
This was not due to genetics, but rather due to environmental factors such as
disease, accidents, and malnutrition. Death during childbirth was common in
women and many children did not live past infancy due to disease or trauma.
Even when people did attain old age, they were likely to die quickly from
untreatable disease or infection.
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| The Industrial Revolution |
Differences in life expectancy
between different parts of the world are caused mostly by differences in public
health services, medical care and diet. Much of the excess mortality (higher
death rates) in poorer nations is due to war, starvation, and diseases such
as malaria and AIDS.
The effect of AIDS is especially notable
on life expectancy in many African countries. If HIV was not a factor, the
life expectancy at birth for 2010–2015 would have been 70.7 years
instead of 31.6 in Botswana, 69.9 years instead of 41.5 in South Africa
and 70.5 years instead of 31.8 in Zimbabwe.
Even in countries where there is a
majority of people are of European ethnic background, such as the United
States, Britain, or Ireland, those with an African ethnic background
still tend to have shorter life expectancies than their European counterparts.
In the United States, for instance, 'Euro-Americans' have a life expectancy of
78.2, but 'African Americans' only 73.6 years.
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| Mozambique and Malawi |
Apart from 'ethnicity' (a large part of
which is genetic make-up), economic and political factors also have significant
bearing on life expectancy. The lowest life expectancies are in the African
countries of Malawi and Mozambique where the average life span is just 36
years. The highest life expectancies are in Japan, Andorra and San Marino,
where life expectancies are between 80 and 83 years.
It is evident that many factors
contribute to an individual's longevity, including gender, genetics, hygiene
and access to health care, diet and nutrition, lifestyle and exercise as ell as
crime rates. In developed countries, life expectancy varies between 77 and
83 years (ex Canada 81.29 years in 2010); in developing countries, life
expectancy is much more variable between 32 and 80 years (ex Mozambique 41.37
years in 2010).
Many studies suggest that longevity is
based on two major factors, genetics and lifestyle choices. Studies
involving twins show that approximately 20-30% of an individual’s lifespan is
related to genetics and the rest is due to individual behaviors and
environmental factors. After reaching the age of 80 years, lifestyle
plays almost no role in health and longevity and almost everything that 'keeps
you going' in advanced age is due to genetic factors.
Scientific and objective study of
longevity has only been practised in recent decades. Prior to that, historical
accounts of long-lived 'methusalahs' are impossible to verify.
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| Jeanne Calment |
The longest-lived well documented case
is that of a French woman Jeanne Calment who died in August 1997 at
the age of 122 years, 164 days. Of the ten documented 'long-livers', all are
female and all are from developed countries (France, US, Canada, Japan) with
the exception of one from Ecuador.
But does all this mean that we are
'supposed to die', that we are 'not supposed to live to 122 years'? Why then do
members of some species live hundreds, even thousands of years and why do some
of our own species outlive the rest of us?
Aubrey David Nicholas Jasper de Grey is
an English author and theoretician in the field of old age research and
the Chief Science Officer of the 'Strategies for Engineered Negligible
Senescence (SENS) Foundation'.
He is best known for his view that human
beings could, in theory, live to lifespans far in excess of 122 years, perhaps
even to thousands of years. Indeed, Grey claims that the first human who
will live up to 1,000 years is probably already alive now, and might even be
today between 50 and 60 years old.
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| Aubrey David Nicholas Jasper de Grey |
De Grey claims to have identified seven
types of molecular and cellular damage caused by essential metabolic processes
- 'The Seven Deadly Things' (that number '7' once again! see post: Seven Sages and Four Horsemen):
1. Cancer-causing nuclear
mutations: Changes (mutations) to the nuclear DNA (nDNA), the molecule
that contains our genetic information, or to proteins which bind to the
nDNA can lead to cancer. For the purposes of SENS, the effect of
mutation which really matters is cancer which can spread and become deadly. The
solution would be a 'cure for cancer'. The SENS program focuses on regenerative
medicine treatments to lengthen telomeres (see cellular senescence,
below), protecting the ends of the DNA molecule.
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| Telomeres |
2. Mitochondrial mutations: Mitochondria
are tiny 'energy factories' within our cells which contain their own
genetic material. Mutations to mitochondrial DNA (mDNA) can affect a cell’s
ability to function properly. Because of the highly oxidative environment in
mitochondria and the lack of the repair systems normally found in the cell nucleus
but absent in mitochondria, mitochondrial mutations are believed to a be a
major cause of progressive cellular degeneration and ageing. Moving the mDNA
into the cellular nucleus where it would be better protected might
solve this problem.
3. Intracellular aggregates (junk
inside the cell): Our cells are constantly breaking down molecules
which are no longer useful or which can be harmful and which can’t be digested.
These molecules accumulate as junk inside our cells, resulting in diseases such
as atherosclerosis and macular degeneration. Removal
of this intracellular junk by adding new enzymes (taken from bacteria and
molds) to the human cell would be the solution.
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| Atherosclerosis |
4. Extracellular aggregates (junk
outside of the cell): Harmful junk can also accumulate outside of our
cells. The amyloid plaque seen in the brains of Alzheimer's patients
is an example. This extracellular might be removed by enhancing the immune
system and by using drugs to break chemical bonds within the junk. The
larger junk in this class could also be removed surgically.
5. Cell loss: Some of the
cells in our bodies cannot be replaced, or can only be replaced very slowly.
This decrease in cell number causes problems such as a weakened heart and Parkinson's
Disease. This cell depletion can be partly corrected by exercise and growth
factor administration but more complete cell replacement would require stem
cell therapy and 'tissue engineering'.
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| Parkinson's Disease |
6. Cellular senescence: Cell
senescence is a phenomenon where the cells are no longer able to
divide but also do not die. Often, these cells secrete harmful. Type 2
diabetes and joint degeneration (arthritis) are examples of this
phenomenon. These same cells sometimes do not respond to usual
signals within the organism as part of a process called apoptosis (programmed
cell death) where the cells are genetically instructed to destroy themselves.
Cells in this senescent state could be
eliminated by forcing them to apoptose by inserting 'suicide genes' or vaccines
into these cells, allowing healthy cells to multiply and replace them.
Cellular senescence relates once again to the telomeres
which are pieces of DNA that act as a kind of protective end to the chromosome.
When a cell divides the telomere curls back around to continue to protect the
end but each time the cell divides, the telomere gets shorter. Eventually the
telomere becomes too short to curl back far enough and can no longer properly
protect the chromosome.
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| Leonard Haflick |
Cancer cells are be able to produce
an enzyme called telomerase that the cancerous cell uses to rebuild
its telomeres and continue dividing beyond its assumed 'allotted' amount.
The reality is that in all multicellular organisms, no
individual cell is meant to live forever. There is, a programmed cell death
(apoptosis) genetically ingrained into each cell. This has been defined as
the Hayflick limit (Hayflick Phenomenon), the number of times a
normal cell population will divide before it stops, presumably because the
telomeres shorten to a critical length.
The Hayflick limit was discovered
by Leonard Haflick in 1961, at the Wistar Institute in
Philadelphia. Hayflick showed that each cell division shortens the
telomeres on the DNA of the cell, eventually makes cell division
impossible, this shortening correlating with the ageing process. Between
50 and 70 billion cells die each day due to apoptosis (the Hayflick limit)
in the average human adult.
7. Extracellular crosslinks: Cells
are held together by special linking proteins. When too many cross-links form
between cells in a tissue, that tissue can lose its elasticity and cause
problems such as arteriosclerosis and presbyopia. De Grey proposes to
develop enzymes to break links caused by sugar-bonding, known as advanced
glycation end-products and other forms of chemical linking.
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| The SIR2 Gene |
But despite all these somewhat
'specific' points which, if addressed, may prolong life, science does not
really know exactly why we age. What is known is that there are a large
number of gene sequences which play a role in the process of aging.
One of the major contributors to aging
may be the SIR2 gene (producing the SIR2 protein) and its effects on
metabolism. The SIR2 gene is a 'controller', turning on some genes within a
cell and turning off others. Other research has found correlations between
a the use of calories in a cell and life span (in flies), doubling not
only the life span of the insect but also their 'middle age'.
Aubrey de Gray may have recognized some
of the factors which result in ageing and pointed in the direction of possible
solutions but there is already clinical research which has produced results.
The University of Texas
Southwestern Medical Center is researching the use of telomerase in
cells other than cancerous cells in the hope of extending the ability of these
healthy cells to continue to divide. The idea is that if we can stay healthier
for longer then the likelihood is that we can, in fact, live longer.
Three types of cloning are
being investigated:
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| Dolly the Sheep |
1. Recombinant DNA Technology or DNA Cloning involves
cloning a specific gene.
2. Reproductive Cloning transferred genetic material from the nucleus
of an adult donor cell to a enucleated egg. This egg is then stimulated to
encourage division and once a suitable stage has been achieved, the egg is
transferred to a uterus and brought to term. This technique was used to
produce Dolly the sheep.
3.Therapeutic Cloning (embryo cloning) is similar to reproductive
cloning but the embryo is not returned to the uterus and is not intended to be
brought to term. The embryo is used as a source for embryonic stem cells which
can then be used to produce any kind of organ or tissue which will have a DNA
match to the cell donor.
Organ production is already a
reality. It has been revealed that a cell taken from an udder, for
instance, could produce a liver or heart or, as in the case of Dolly, a whole
sheep. If we can genetically engineer or clone a new organ to replace the one
that is faulty, we could ultimately live a very much extended life.
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| Human Ear on the Back of a Mouse |
In 1997, at the University of
Massachusetts, researchers were able to grow a human ear on the back of a
mouse. The study was designed to serves as a model for tissue engineering. The
mouse had a defective immune system and was unable to reject the human tissue.
Medicine can already, replace some
defective organs by transplanting a donated organ but the donor organ must be a
tissue match. If the donor tissue and the recipient's tissue don't match then
the organ is rejected and therefore useless.
Human urinary bladders have
been created and inserted with success into recipients using their own cloned
cells. In 2000, the scientists who created Dolly created cloned
pigs, pig organs being the mostly likely ones to be able to be used for
xenotransplantation (genetically modifying animal organs, tissue and cells for
use in human transplantation).
Ultimately while it does not
strictly lengthen our life span, whole body cloning may provide the ultimate in
immortality. If we can extract our DNA and transplant or store it we really do
have the opportunity to 'live forever'.
But there are perhaps more 'practical'
ways to extend life expectancy already available - at least in certain
non-human species. Resveratrol, a compound found in the skin of red
grapes was reported to extend the lifespan of yeast, worms, and flies.
Calorie restriction in mice has
been shown to extend life span by around 40% even when initiated late in the
animal's life. The activity of the gene SIR2 has been shown to increase under
calorie restriction (see 'Extracellular crosslinks', above).
Intermittent fasting, such as alternate
day fasting, resulting in low-calorie intake can also extend life span.
Dietary restriction of the amino
acid methionine also produce extended longevity in mice.
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| Methionine |
A certain breed of mouse with
an absence of growth hormone has been shown to live 60-70% longer
than the standard laboratory mouse species. This research demonstrates that the
hormone insulin and insulin-like growth factor (IGF-1)
along with growth hormone are important to the operations of metabolism
that determine life span.
In 2008, Spanish researchers were able
to extend life span in lab mice by 50% through a combination of an enhanced
telomerase enzyme and p53 gene. Telomerase, produced by cancer cells extends
cell life but creates a cancer while the p53 gene is an anti-cancer gene
that normally reduces life span, lowering the risk of cancer. The
telomerase-p53 experiment effectively demonstrates a point of balance between
extended life span and cancer.
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| The p53 Gene |
Inactivation or reducing the activity of
the CLK-1 gene (originally noted in C. elegans) found in
mitochondria boosts mouse longevity by 30%.
A Russian researcher has demonstrated a
form of antioxidant that can be targeted to the mitochondria when
ingested. SkQ, the mitochondrially targeted antioxidant boosts mouse life
span by 30%.
Genetically manipulating the levels
of a naturally produced antioxidant catalase in order to increase its
level in the mitochondria increases mouse life span, presumably by soaking up
some portion of the free radicals produced by mitochondria before they can
cause damage. The mice lived 20 percent longer than the normal variety.
An enzyme called pregnancy-associated
plasma protein A (PAPP-A) which operates within the insulin-like
growth factor system, when removed, extends a mouse's life span by 30%
without reduced calorie intake and, at the same time, reducing the incidence of
cancer.
Mice lacking the gene for the adenylyl
cyclase type 5 (AC5) protein live 30% longer. This heart gene (AC5),
when 'knocked out', besides allowing the mice to live longer, also seemed to
prevent heart stress as well as bone deterioration that often accompanies
ageing.
The drug metformin (commonly
used to treat diabetes) acts similarly to calorie restriction in mice,
resulting in 10% gain in maximum life span.
Fat-specific insulin receptors, when
'knocked out' in mice (FIRKO mice) result in less visceral (around the
internal organs) body fat than normal mice, even when fed the same number
of calories and live almost 20% longer.
Mice which underwent surgical removal
of visceral body fat also experienced longer life spans as well as
less kidney disease.
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| Visceral Body Fat |
Over-expression of the
enzyme PEPCK-C (phosphoenolpyruvate carboxykinase) in genetically
manipulated mice resulted in a more than 50% life extension but these same
mice could also run faster, ate 60% more, had 1/2 the body weight and 10% the
body fat of control (normal) mice.
The major factor thought to be responsible
for the longevity of the PEPCK-C minus mice was the low concentration of
insulin in the blood of these mice which was maintained over their lifetime of
hyperactivity.
Other discoveries have also been made.
In 2006, it was reported that scientists may have found a fountain of youth, a
drug that appears to slow and even reverse the physical effects of ageing. In
tests on nearly 400 men and women aged 65 and older, drug giant Pfizer's
experimental pill significantly boosted levels of a hormone behind the growth
spurt at puberty.
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| Pfizer |
Volunteers given the hormone stimulator
called capromorelin experienced a 1.4 kilogram average increase in
muscle mass. After six months of treatment, the volunteers showed a
significant improvement in balance activities, walking 'heel to toe'; after 12
months, they were better able to climb stairs.
An increasing human life span has been
happening for quite some time. One hundred years ago, the average
life expectancy in America was between 47 and 53. One hundred years before
that, it was around 32. In the past 200 years we have almost tripled our
expected life span which has increased from the low of 32 to today's high of 87
years.
But just living longer is not really
enough. Any person who has the desire to live a long life also wants a life in
which he/she can stay young, fit and healthy. Otherwise that person may end up
like Tithonus, wasted and withered, reduced to a mere shadow of himself,
growing older and older and ever more feeble.
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| Tithonus, Wasted and Withered |
Today, some of the most profitable
companies in the world are those which produce and market beauty and health
pills and potions. Some of these 'youth treatments' may be effective; most are
nothing more than a waste of money.
Through the use of diet, genetic
therapy, biotech, improved health care and lifestyle changes, life extension
will continue to increase. But most of us will likely not be able to lean back
and take a passive role, having certain of our genes 'knocked out' or manipulated
or using drugs to restrict our calorie intake.
What science is certain of today is that
(too much) fat is bad, especially if it is 'on the inside' (visceral ie 'beer
gut'); little or no exercise is a ticket to heart disease, diabetes (and probable
shortened life); eating just enough (with a balanced diet) to maintain your
ideal body weight (a type of calorie 'restriction') is all that is
needed; certain foods may be beneficial (grapes? red wine?) and others harmful
(foods with high fat content).
Certain activities are just plain bad
for you (tobacco consumption, use of illicit drugs) and will likely be a direct
cause of (early) death.
But proper living will not likely
ever achieve what mankind has sought since before the beginning of history. A
race to unlock genetic clues behind living to 100 and beyond is set to begin. A
US team has announced that it will compete for the $10m Genomics X Prize. Genetic
entrepreneur Dr. Jonathan Rothberg is entering the challenge to
identify genes linked to a long, healthy life. Contenders will be given 30
days to work out the full DNA code of 100 centenarians at a cost of no more
than $1,000 per genome.
The race for long life will begin in
September 2013.
One last thought-provoking idea about
how to extend life span, at least for males.
Researchers in South Korea have analysed
the genealogical record of eunuchs, looking at the lifespans of 81 eunuchs born
between 1556 and 1861. The average age was 70 years, including three
centenarians (the oldest reached 109 at time of death). It seems that
castration had a huge effect on the lifespans of these Korean men
who lived up to 19 years longer than uncastrated men from the same social
class and even outlived members of the royal family.
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| Ancient Chinese Mural Depicting Eunuchs |
By comparison, men in other families in
the noble classes lived into their early 50s. Males in the royal family lasted
until they were just 45 on average.
One thought is that male sex hormones
such as testosterone, which are largely produced in the testes, could be
damaging to the point that male hormones may indeed shorten life
expectancy. The researchers postulated that the hormones could weaken the
immune system or damage the heart. Castration would prevent most of
the hormone from being produced, protecting the body from any damaging effect
and prolonging lifespan.
Click on the link below for an
interesting TED talk by Aubrey David Nicholas Jasper de Grey.
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