Calorie Restriction and Life Span
Life Expectancy (an abstract from
One hundred and twenty years, as far as we know,
is the longest that anyone has
ever lived. A man in Japan, Shirechiyo Izumi,
reached the age of 120 years, 237 days in 1986, according to
documents that most experts think are authentic. He died after developing pneumonia.
Long lives always make us wonder: What is the secret? Does it lie in the genes? Is it where people live or the way the live - - something they do or do not do? Eat or do not eat? Most of the scientists who study aging, gerontologists, say the secret probably lies in all of the above - - heredity, environment, and lifestyle.
But gerontologists also ask other and more difficult questions. For example, if the 120 year old had not finally succumbed to illness, could he have lived on and on? Or was he approaching some built-in biological limit? Is there a maximum human life span beyond which we cannot live no matter how optimal our environment or favorable our genes?
Whether or not there is such a limit, what happens as we age? What are the
dynamics of this process and how do they make life spans short, average, or long? Once we understand these dynamics, could they be used to extend everyone's life span to 120 or even, as some scientists speculate, to much greater ages? And finally for all of us, the most important question: How can insights into longevity be used to fight the diseases and disabilities associated with old age to make sure thie period of life is healthy, active, and independent?
Average life span and live expectancy in the United States have grown dramatically in this century, from about 47 years in 1900 to about 75 years in 1990. This advance is mostly due to improvements in sanitation, the discovery of antibiotics, and medical care. Now, as scientists make headway against chronic diseases like cancer and heart disease, some think it can be extended even further.
U.S. Life Expectancy
|Source: Dept of Health and Human Services
Maximum human life span seems to be another matter. There is no evidence that it has changed for thousands of years despite fabled fountains of youth and biblical tales of long-lived patriarchs. However, very recently, the dream of extending life span has shifted from legend to laboratory. As gerontologists explore the genes, cells, and organs involved in aging, they are uncovering more and more of the secrets of longevity. As a result, life extension may now be more than the stuff of myth and the retardation of disease and disability, realistic goals.
In 1989, at Veterans Administration hospitals in Milwaukee and Chicago, a small group of men aged 60 and over began receiving injections three times a week that dramatically reversed some signs of aging. The injections increased their lean body (and
presumably muscle) mass, reduced excess fat and thickened skin. When the injections stopped, the men's new strength ebbed and signs of aging returned.
What the men were taking was recombinant human growth hormone (GH), a
synthetic version of the hormone that is produced in the pituitary gland and plays a critical part in normal childhood growth and development. Now the researchers are learning that
GH, or the
decline of GH, seems also to play a role in the aging process in at least some individuals.
The idea that hormones are linked to aging is not new. We have long known that some hormones decline with age. Human growth hormone levels decrease in about half of all adults with the passage of time. Production of the sex hormones estrogen and
testosterone tends to fall off. Hormones with less familiar names, like melatonin and
thymosin, are also not as abundant in older as in younger adults.
New territory, unexplored or only sketchily mapped, lies ahead. As
gerontologists isolate and characterize more and more longevity - and aging-related genes in laboratory animals, insights into genes and gene products important in human aging will emerge. Comparable human genes will be identified and mapped to chromosomes.
This information will be useful in designing both genetic and non-genetic
interventions to slow or even reverse some aging-related changes. Already, for example, a study by Helen Blau of Stanford University has shown that muscle cells can be
genetically modified and injected into muscle where they will produce and secrete human growth hormone. Non-genetic strategies will include the development of interventions to
reduce damage to cellular components, such as proteins, nucleic acids, and lipids.
Normal aging will be more closely defined. For instance, at NIA's
Gerontology Research Center, the behavior of the cells that line blood vessels during aging is now providing clues to the stiffening of blood vessels that occurs with age as well as insights into vascular disease. As key biomarkers of aging are identified, researchers will be able to use them to test interventions to slow aging. Studies will begin to delve more deeply into differences in aging between the sexes and among ethnic groups.
In short, gerontologists will be charting the paths
and intersections of genetic,
biochemical, and physiologic aging. What they find will reveal some of the secrets of aging. It may lead to extended life spans. It will very certainly contribute to better
health, less disability, and more independence in the second fifty years of life.
Calorie Restriction and Life Span
by Tanya Zilberter
more information of calorie restriction
Very Low Calorie Effect on Health and Life Span
A calorie restriction effect on longevity is a very well documented topic of experimental
biology. It is important to know that life span researchers deal mostly with small size
any meals since their generations change much faster than in larger size animal species. It is also important that only restriction as
serious as 30 to 60 percent of "all you can eat" amount can cause significant improvement in health and longevity.
It was first demonstrated in insects, where it yielded up to a 300% increase in life span;
then in young small size mammals such as mice and rats, where
results were more modest but still impressive. Later the results on adult animals appeared, yet more modest, but still
As to the human outcome, published epidemiological studies have reported evidence of reduced mortality rates in persons who have lost weight, regardless of whether the weight loss was due to decreased calorie intake or increased energy expenditure (1).
These data are consistent with experimental results where exercise increased average longevity of female rats, despite increased food intake (2).
This consistency is probably the reason for hopes arising from
numerous animal data
showing benefits of calorie restriction in animals, including improvement in immune status, anti-cancer defense system and decrease in the occurrence of general disease. The hope, if not for increased longevity, is at least for decreased mortality.
Can we use calorie restriction to improve health and to live longer? A daily calorie
restriction of 30 to 60 percent seems to be too hard a sacrifice. Perhaps this is why new
hope arose when preliminary information about developing an anti-aging drug mimicking effects of
semi-starvation leaked into mass media.
Dr. Masoro from the Department of Physiology and Aging Research, University of Texas, reviewed 54 scientific articles and concluded: "A spectrum of findings indicates that dietary restriction retards the
aging processes of mice and rats. It also maintains many physiological processes in a youthful state and, most strikingly, retards or prevents almost all age-associated disease processes." (3)
However, it's too soon to use the calorie restriction as a strategy to improve health and prolong life.
"Due to the interrelationships between disease and older age, and the limitations of existing research in this area, most life extension
strategies are untested hypotheses. Many strategies merit scientific inquiry, but they cannot be recommended for use. More extensive research is necessary to assess their safety, effectiveness, and
socio-economic impact, and to resolve ethical controversies before they can be considered applicable in humans." (Pharmacotherapy, 16(2):183-200, 1996)
Can Adults Benefit from Calorie Restriction?
Research results showed that when calories are restricted in older animals, an increase in life span is still observed; though not as great as that observed in the animals that were calorie restricted since they were young. The data of this research suggests there may be a level of maturity, or a stage in the aging process, after which caloric restriction no longer increases longevity. (6) Restricted nutrient intake may have beneficial effects on alults' degenerative disease, autoimmune processes, susceptibility to infection and survival rate after infection. (New Horizons, 2(2):257-63, 1994) Adult rats fed the calorie restricted yet nutritionally balanced diet ate fewer meals but consumed more food during each meal. They
also spent more time eating during each meal. The average body temperature per day was significantly lower in restricted rats. However, they moved around significantly more than the rats that were fed as much as they pleased, so they spent more energy during the day.
Is VLCD stressful?
Yes, but it seems to be a good stress. Restriction of food intake to the degree that it
extends life span is associated with same protective mechanisms mobilized by stress. In
another research conducted by the same university, results indicate that at least one
inflammatory reaction, an edema, is attenuated by food restriction (60 percent of adlibitum calories) and are consistent with the
hypothesis that food restriction enhances a
potentially protective glucocorticoid activity. (Journals of Gerontology, Series A, Biological Sciences & Medical Sciences. 50(2):B79-82, 1995)
So, How does it Work?
The mechanism of action of caloric restriction remains unknown;
owever, data suggest that cellular functions are altered in such a way that destructive by-products of
metabolism are reduced, and defense or repair systems are enhanced by this nutritional
manipulation. (Clinics in Geriatric Medicine, 11(4):553-65, 1995))
The amount of oxidative damage increases as an organism ages and is postulated to be a
major causal factor of senescence. Restriction of caloric intake lowers levels of
oxidative stress and damage, retards age associated changes, and extends the maximum life span in
mammals. Animal and human studies suggest potential benefits of
dietary restriction, exercise, antioxidants, hormones and deprenyl.
Does deprenyl mimic at least some of calorie restriction effects? Probably, thinks Dr.
Masoro. "Dietary restriction protects against oxidative damage and oxidative damage is
probably an inevitable component of fuel use." So does deprenil, though in rather narrow way. Deprenyl (selegiline) is a neuroprotective drug an inhibitor of brain
monoamine oxidase B (MAO-B). That means it inhibits a very particular enzyme
promoting oxidation of the brain chemical monoamines, which are very important in many vital functions, including cognition.
Dietary restriction was found to retard age associated decline of sensory and
movement coordination, and improve performance of aged mice on learning problems. "Studies in aged calorie restricted mice indicated that lowering of protein oxidation by calorie restriction could be reversed within a time frame of three to six weeks. These findings suggest that the beneficial effects of dietary restriction upon brain function and life span may depend upon its ability to acutely reduce steady state levels of oxidative stress." (Archives of Biochemistry & Biophysics, 333(1):189-97, 1996)
1. Annals of Internal Medicine, 119(7 Pt 2): 731-6, 1993
2. Journal of Gerontology, 48(3): B97-100, 1993).
3. "Dietary Restriction and Aging," Journal of the American Geriatrics Society, 41(9):
4. Journals of Gerontology, Series A, Biological Sciences & Medical Sciences.
50(3):B148-54, May 1995
5. Journals of Gerontology, Series A, Biological Sciences & Medical Sciences.
6. Aging. 7(2):136-9, 1995