Tag Archives: gerontology

Caloric Restriction: The defense against aging

Caloric Restriction: The defense against aging

Worried about getting old? It’s simple. Eat less and you could live longer. This is the view held by an increasing number of medical professionals, scientists and nutritionists around the world including experts at the Calorie Restriction Society. These beliefs are based on extensive research which suggests that caloric restriction (CR) can actually slow aging and reduce the incidence of disease, ultimately prolonging life!

CR has been investigated by gerontologists for more than 60 years and provides the only intervention tested to date in mammals (typically mice and rats) that repeatedly and strongly increases maximum life span while retarding the appearance of age-associated pathologic and biologic changes. Although the large majority of rodent studies have initiated CR early in life (1-3 mo of age), CR started in mid-adulthood (at 12 mo) also extended maximum life span in mice. There is evidence to suggest that age-associated increases in oxidative damage may represent a primary aging process that is weakened by CR. With regards to testing on primates, recent studies in monkeys subjected to CR support the notion of human translatability.

CR should not be confused with regular weight loss diets. In fact, weight loss is regarded as a side effect, not a goal. The main objective is to achieve a longer and healthier life by eating fewer calories, while maintaining a regular balance of vitamins, minerals and other essential nutrients. Following this diet brings about a reduction in the white adipose tissue mass and this has been proposed as a principal factor in longevity.

The pathways influenced by caloric restriction

The proteins altered by CR seem to be associated with several different cycles, including the glucose and lipid metabolic pathways which were consistent with increased lipid biosynthesis. The expression of proteins involved in the production of Oxalacetate and NADPH and in lipolysis and lipid biosynthesis was enhanced. In addition, certain insulin receptors were also increased by CR which was consistent with a higher response to lipogenic stimuli.

Other protein expression changes induced by CR gave improved protection against oxidative stress by halting the age-associated reduction in the levels of several antioxidant enzymes and decreasing the levels of stress-induced proteins.

Both CR and aging also changed the expression of proteins involved in the cytoskeleton, iron storage and energy metabolism as well as other proteins with currently unknown functions in adipose tissue.

The CR-induced changes are in line with reported microarray studies and will help to understand the molecular mechanisms behind the lifetime extension and the suppression of the effects of aging.

In the long term, the results could also lead to the identification of novel biomarkers of aging and possible targets for mimetics of CR that could provide the same outcome: an extended lifespan, without having to follow a rigorous and controlled diet.

Read more about calorie restriction and the molecular pathways that slow aging, improve health

Maria Konovalenko


Filed under Article, Life Extension, Science

Reverse Aging of Human Muscle Tissue

In this article, we re-examine a study by scientists from the University of California, Berkeley that had identified critical biochemical pathways linked to the aging of human muscle. By manipulating these pathways, the researchers were able to turn back the clock on old human muscle, restoring its ability to repair itself!

The study shows that the ability of old human muscle to be maintained and repaired by muscle stem cells can be restored to youthful vigor given the right mix of biochemical signals. Professor Irina Conboy, a faculty member in the graduate bioengineering program that is run jointly by UC Berkeley and UC San Francisco, is the head of the research team that conducted the study.

Previous research that Conboy had done in animals, revealed that the ability of adult stem cells to repair and replace damaged tissue is governed by the molecular signals they get from surrounding muscle tissue, and that those signals change with age in ways that preclude productive tissue repair. Those studies also demonstrated that the regenerative function in old stem cells can be revived given the appropriate biochemical signals!

What was not clear until this study was whether similar rules applied for humans.  Unlike humans, laboratory animals are bred to have identical genes and are raised in similar environments.  Moreover,  the typical human lifespan lasts seven to eight decades,  while lab mice are reaching the end of their lives by age 2.

Working in collaboration with Dr. Michael Kjaer and his research group at the Institute of Sports Medicine and Centre of Healthy Aging at the University of Copenhagen in Denmark, the UC Berkeley researchers compared samples of muscle tissue from nearly 30 healthy men who participated in an exercise physiology study. The young subjects ranged from age 21 to 24 and averaged 22.6 years of age, while the old study participants averaged 71.3 years, with a span of 68 to 74 years of age.

The researchers discovered that in the legs that remained immobile, mature stem cells used for repairing muscle tissue and restoration were present in quantities of roughly half as much in older muscle tissue as they were in the youthful samples. The variance was even more wide spread when the exercise period was factored in. The youthful tissue had approximately four times the amount of redevelopment cells that would vigorously mend damaged tissue when evaluated against the aged muscle tissue that contained vigorous stem cell activity.

The researchers further examined the response of the human muscle to biochemical signals. They learned from previous studies that adult muscle stem cells have a receptor called Notch, which triggers growth when activated. Those stem cells also have a receptor for the protein TGF-beta that, when excessively activated, sets off a chain reaction that ultimately inhibits a cell’s ability to divide. The researchers said that aging in mice is associated in part with the progressive decline of Notch and increased levels of TGF-beta, ultimately blocking the stem cells’ capacity to effectively rebuild the body.
This study revealed that the same pathways are at play in human muscle, but also showed for the first time that mitogen-activated protein (MAP) kinase was an important positive regulator of Notch activity essential for human muscle repair, and that it was rendered inactive in old tissue.

MAP kinase [or MAPK] is commonly known to biologists in the developmental field due to it being an essential enzyme where organ growth is concerned in various species, some as atypical as nematodes, fruit flies and rodents. For aged muscle in humans, MAPK quantities are reduced so the Notch connection corridor remains un-stimulated and the stem cells don’t carry out the muscle restoration work as preprogrammed.

Conboy says: “Thanks to these discoveries, we now know that the MAPK pathway plays a key role in regulation and aging of human tissue regeneration. In practical terms, we know that to enhance regeneration of old human muscle and restore tissue health, we can either target the MAPK or the Notch pathways”

Read more about the Berkely study and the reverse aging of human muscle tissue.

Maria Konovalenko


Filed under Article, Science, Tissue rejuvenation

I refuse the invitation to my grave

In the September issue of Scientific American, Tom Kirkwood came out with an article about human aging named “Why can’t we live forever?” His disposable soma theory says that the body is mortal because its cells are specialized. He believes the Body makes a choice where to allocate resources: to immortality or reproduction. However, right now people have unlimited resources and evolution is faster as it has switched to a large extent to the intellectual level.

It’s not obvious how the disposable soma theory explains the fact that women live longer on average, although reproduction is much more expensive as compared to men in terms of resources. Another remarkable example is the queen of social insects (bees, termites, ants). Despite devoting a huge portion of resources to reproduction of thousands of offspring, the queen can live hundreds of times longer than sterile female workers that serve to her needs.

I fundamentally disagree with the following idea made by the author: “The goal of gerontology research in humans, however, is always improving health at the end of life, rather than achieving Methuselean life spans.”

This is a traditional stance taken by the hawks of the conservative wing of gerontologists: to oppose the quality of life to longevity. This is the biggest mistake in gerontology. The quality of life and longevity are closely related. If the quality of life is high in the biomedical sense, then why would the person suddenly die? Besides, many experiments on model animals show that the interventions leading to life extension also led to improved reproduction and increased activity. Essentially, an improved quality of life for the animal.

The reasoning behind such statements is based on an “acceptance of one’s own death”, which the author is calling for. Since we cannot radically increase longevity right now, then let’s consider it as ‘unnecessary’.

Fighting for longevity automatically means fighting for an increase of the quality period of life. Human life is the absolute value. Therefore a decrease in viability and declined health cannot serve as consent to die. Just because a man is unable to walk, doesn’t mean he should give up on life. Quite the opposite, our goal should be to find a way to restore living functions.

Denial of the radical life extension idea amounts to intellectual cowardice or fear to be perceived as a ‘black sheep’, and ignoring the advances of modern science. Nematode, drosophila and life spans in mice were significantly increased. Yes, human anatomy / biology is way more complex, but no sensible person would claim that life extension is a simple task. Tom Kirkwood says: “Solutions will not come easily, despite the claims made by the merchants of immortality who assert that caloric restriction or dietary supplements, such as Resveratrol, may allow us to live longer.” One shouldn’t confuse supporters of human immortality with the merchants of curative elixirs.

We, the supporters of radical human life extension, are the first to affirm that solving the problem of aging is an extremely complicated task. Implementation of a complex interdisciplinary research program into aging, significantly enlarging the scope of the field and also increasing public awareness about the goals of biogerontology are urgently needed. We believe that development of regenerative medicine and research into genome regulation can generate impressive results within a relatively short period of time – as soon as the next decade. The pace of this important research is to a large extent dependant on the position, the definition of objectives and overall mutual agreement within the global scientific community that:

«The goal of gerontological research on humans is radical human life extension».


Filed under Immortalism