Perhaps it is almost laughable to think of the 15th century explorer Ponce de Leon and his search for the Fountain of Youth. Popular folklore contends the Spanish explorer found Florida instead of his intended discovery. Yet today the quest for youth and longevity must be at least a trillion-dollar industry as individuals and companies alike seek to discover anti-aging remedies.
Is there a balm for the aging process? Can we live not only longer, but also retain the health, vigor, and appearance associated with youth? The answers to those questions are not entirely known; however, scientists are earnestly trying to identify the biological factors responsible for aging.
Dr. Suresh Rattan of Denmark derived a formula that summarizes the elements of which we are now aware that influence aging. Rattan’s formula consists of the following: E=GMC2, where E is eternal life;
G represents genes; M stands for milieu or the environment in which organisms live; and C is chance.
E equals caloric restriction
It has been known for more than 70 years that caloric restriction with adequate nutrition extends lifespan. Caloric restriction may be defined as a dietary regimen that limits the intake of calories without incurring malnutrition. The reduction in total food intake can involve restriction of major food categories, such as proteins, fats, or carbohydrates as well as periodic fasting. Dietary or caloric restriction (CR) is the sole intervention documented to increase lifespan in a variety of species, including yeast, flies, fish, mice, and dogs. The results from model organisms may be applicable to humans, and currently, specific findings related to dietary restriction are being studied in human volunteers.
CR appears to protect against diabetes, cancer, and cardiovascular disease. The basic mechanisms of these effects are not well understood; however, the insulin-signaling pathway appears to mediate and regulate CR. Insulin regulates the blood glucose level through a complex signaling cascade — insulin/IGF-1/growth hormone axis — that includes insulin-like growth factor (IGF-1), similar in protein structure to insulin, and growth hormone.
G is for Genes
Research delineating the genetic basis of aging is in the early stages, but scientific evidence indicates that genes are only part of the equation. Genes can be influenced and acted upon by external conditions, such as CR, physical activity, sun (ultraviolet radiation), amount of sleep, and even the availability of oxygen to the tissues and cells. Genes associated with aging and increased lifespan have a variety of functions in a range of biochemical pathways involving maintenance and repair responses (MRSs) including stress and immunity. Other examples of MRS functions are wound healing and replacement of dead cells. Although many genes may show evolutionary conservation, the challenge remains to determine which ones will be useful in human anti-aging therapies and solutions.
Milieu or Environment
The milieu consists of the biochemical environment in which living organisms function and encompasses other factors that influence the aging process beyond genes. One such factor is the field of epigenetics. Epigenetics refers to heritable changes in the phenotype in which the DNA sequence is unaltered. By heritable changes, it is thought that these variations persist during cell division, but are not necessarily passed on to future generations from parents to child.
Telomere shortening is also thought to be involved in aging, although the precise mechanisms are still being researched. Telomeres are unique structures at the end of linear chromosomes, composed of repetitive DNA, which protects the chromosome ends from deterioration. Shortening of telomeres can lead to chromosomal breakage and changes in gene expression over time.
Adult stem cells may also play a role in mammalian aging. An adult stem cell is defined as an undifferentiated cell, found among differentiated cells in a tissue or organ, capable of renewing itself with the potential to differentiate into some or all of the major cell types of the tissue or organ. The controversial theory is that as a consequence of stem cell aging and/loss, tissue maintenance and repair are decreased, resulting in the overall aging of the organism.
Chance
The final component of the Rattan formula is chance. Chance involves randomness, and events beyond the control of mere mortals. Living to 100 years has a genetic component, but it is combined with happenstance, which by definition cannot be regulated.
Maintenance and repair systems (MRSs) keep living organisms in a dynamic state of balance, responding to environmental and metabolic stresses. By identifying the factors that interfere with MRSs and thereby contribute to aging, scientists hope to establish a basis for the formulation of interventions and strategies to alleviate functional decline.
References and Read-more-about-it:
1. Rattan SI. 2007. The science of healthy aging: genes, milieu, and chance. Ann N Y Acad Sci, 1114:1-10. Review.
2. Fontana L, Partridge L, Longo VD. 2010. Extending healthy life span--from yeast to humans. Science. 328(5976):321-6.
3. Katewar SD, Kapahi P. 2009. Dietary restriction and aging. Aging Cell, 9: 105-112.
4. Wilson A, Shehadeh LA, Yu H, Webster KA. 2010. Age-related molecular genetic changes of murine bone marrow mesenchymal stem cells. BMC Genomics, 11:229.
5. Passos JF, Saretzki G, von Zglinicki T. 2007. DNA damage in telomeres and mitochondria during cellular senescence: is there a connection? Nucleic Acids Res, 35(22):7505-13.
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