VitaLongevity
Orentreich
TM
Foundation for the
Advancement of
Science, Inc.
Logo: Life’s blood flows through the hourglass; the stopcock represents the alteration of aging and disease as biomedical research progresses.
March 2007 www.orentreich.org
Life Span Extension advanced age? The answer is that the degree of food
restriction necessary to extend life is so intense that
by Diet animals fed such diets are constantly hungry, and it is
unlikely that human beings would subject themselves to
such profound lifelong discomfort in order to live longer.
The goal of medical care has always been to extend life
either by preventing or treating individual diseases on a However, scientists have continued over the past 50 years
disease-by-disease basis. In fact, though, the overall effect to examine caloric restriction in the hopes of identifying
of completely eradicating a single age-related disease like mechanisms through which this remarkable life span
atherosclerosis or cancer would be an increase of only a extension takes place. If the mechanisms were identified, it
few years in average life expectancy might be possible to invoke them
in the population. Imagine instead that through some other intervention, i.e.,
the rate of aging itself could be The structure of Methionine a caloric restriction mimetic that would
slowed, so that all diseases occurred be more acceptable to people. The
later in life. The result would be a challenge in this approach is that
radical increase in life span far beyond energy is used in so many places and
that which could be achieved by in so many ways that it is
curing some single disease. extraordinarily difficult to single out
key places where reduced energy
Extending Life Span to intake causes life extension.
168 Years
Surprisingly, scientists have known for
An Alternative to
almost 100 years how to slow aging Energy Restriction Emerges
sufficiently to extend life span by Imagine, then, the excitement when
approximately 40%. That corresponds scientists at OFAS discovered another
to a maximum life span in human dietary intervention that extends life
beings of 168 years and an average Figure 1. but which is characterized by well-
life span of approximately 105. Not known metabolic pathways that are
only is life extended, but there is a matching extension in more amenable to analysis. This novel intervention
the quality of life in animals who have been subjected to involves lowering the dietary content of the amino acid
this treatment. What is this seemingly magical treatment? methionine to a level that reduces growth somewhat but
In the early part of the 20th century researchers found that markedly extends life span.
by markedly underfeeding animals they survived longer. By
the mid 1930’s this had been carefully studied, and it was All proteins are composed of chains of building blocks
clear that a reduction in food intake could produce a 40% called amino acids. There are a limited number of
increase in life span in rats. different amino acids that are used to make proteins, and
they can be divided into two broad categories: essential
Since that groundbreaking study scientists have exposed a amino acids, those that an organism cannot make itself but
variety of species to a variety of feeding strategies, and it must ingest, and non-essential amino acids, which can be
has become clear that in all species studied the key is to made internally and so do not need to be consumed. Of
reduce energy (calorie) intake throughout life in order to the essential amino acids, methionine ranks as one of the
achieve a marked increase in survival time. most important since it is used to begin the synthesis of all
proteins. The metabolic pathways that use and degrade
Not surprisingly, most age-related maladies are minimized methionine have been thoroughly studied in many species,
or delayed by long term energy restriction. For example, in including human beings.
rats fed 60% of their normal caloric intake, all cancers
appear approximately 40% later in life, and the animals live, The remarkable thing about dietary methionine restriction
not coincidentally, 40% longer. It is important to note that the is that animals consuming this diet are free to eat all they
range of tumors does not change, only their time of onset. wish and typically consume more calories than usual. This
rules out energy restriction as the explanation for the life
Why is energy reduction not commonly used to retard span extension phenomenon of methionine restriction.
aging and delay the appearance of the diseases of Further, since the animals eat all they want, they are not
hungry! They behave normally but survive 40-45% longer impossible to assemble and consume a low-methionine
than animals consuming “normal” levels of methionine. As diet. Nearly all meat, dairy, and vegetable proteins are rich
expected with any age-slowing intervention, age-related in methionine. Those few that are naturally of low
diseases appear with the usual frequency for the species, methionine content, e.g., soy, as noted above, are usually
just 40-45% later in life, and markers of important processed by the food industry with added methionine to
functions such as immunocompetence are preserved convert them into high-quality proteins. In addition to
further into old age. difficulty in finding and consuming such a diet, there is no
assurance that low-methionine ingestion will be without
In a variety of studies, short term moderate methionine some negative side effects. For example, female rodents
restriction has been shown to produce a variety of receiving this diet are unable to reproduce, and all animals
beneficial actions in animals. For many years it has been fed this diet from a young age are undersized.
known, for example, that reduced methionine intake
sharply retards the growth of solid An even more important question
tumors, most of which are dependent Daily requirement of essential about dietary manipulation of life
on ample methionine availability for amino acids (for college-age males). span concerns the validity of results
growth and invasion. As you might (Other species frequently have other in experimental animals to human
expect, there is research in progress essential amino acid requirements, but beings, i.e., results attained in
to convert this observation into a methionine is always essential.) rodents might not be duplicated in
usable clinical approach to cancer. human beings consuming similar
Name Grams
Vegetarians have known for many diets. There is no certain answer to
Arginine 0†
years that consuming the majority of this problem other than to note that
Histidine Unknown‡
their protein in the form of soy protein both caloric and methionine
Isoleucine 1.30
keeps total body fat low. It is now restriction have been tested in a
Leucine 2.02
clear that this effect is due to the low wide variety of species (ranging from
Lysine 1.50
level of methionine in soy protein and yeast to primates) with good
Methionine 2.02
that enriching soy with methionine success. There are currently studies
Phenylalanine 2.02
increases fat depots. Thus, underway of energy restriction in
Threonine 0.91
methionine probably extends life span monkeys, but since these animals
Tryptophan 0.46
through a combination of effects— live longer than rodents, it will take
Valine 1.50
some specific to specific physiological †Required by infants and growing children. many years to determine whether
conditions, others acting to retard ‡Essential, but the precise requirement is not yet primates respond to energy
aging so that most causes of illness established. restriction with life span extension.
and death are delayed. Early results indicate that some
Table 1.
metabolic changes resemble those
Scientists now have two interventions that slow aging: seen in rodents fed low-energy diets, so there is some
energy and methionine restriction. One of these hope that the longer-term studies will be successful.
mechanisms (energy restriction) is characterized by diffuse
sites of utilization; the other (methionine restriction) must On the assumption that caloric or methionine restriction is
be occurring through some of the well-known pathways of effective in human beings, is there hope for those of us
methionine metabolism. Therefore, it is possible to who have already passed through youth and would like to
compare these two interventions and, hopefully to identify extend whatever remains of our lives with high quality?
key metabolic points amenable to direct specific Drawing from animal experiments, there is some reason
manipulation without the imposition of difficult-to-follow for optimism. In animals, caloric restriction has been
dietary regimens. shown to extend life span even when begun later in life,
although the effect is considerably less robust, and the
Why bother trying to identify the key events involved in life duration of the extension is less than that seen when the
span extension from methionine restriction? Why not just restriction is initiated early in life. Similarly, methionine
consume a low-methionine diet to achieve longer life? The restriction has some life-extending properties when begun
answer to these important questions is that it is virtually in adulthood, but early is much more effective.
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