Biomarkers for Aging-The Aging Process-Part XII
(5/29/09) The World Health Organization (WHO) has issued its world health statistics for 2009 in which they determine the life expectancy of a baby born in 2007 in each country of the world. Leading the life expectancy nations is Japan, where the life expectancy is 83 years.
In second place is San Morino at 82 years, followed by
Andorra, France, Israel, Monaco, New Zealand, Norway, Singapore,
Spain and Sweden at 81 years. In the United States, the life
expectancy for a baby born in 2007 is 78 years. The same life
expectancy is found in Chile, Cuba, Denmark, Kuwait, Slovenia,
and the United Arab Republic.
The WHO also indicated that children younger than 5 account for 20% of the worlds death. This plays out in the low life expectacy years in many of the third world nations, especially in Africa.
(4/10/05)-Census data indicates that the average age of the general population is creeping up. As this population increases in average age, there are domino effects. Total costs of retiree benefits are becoming a serious burden to corporations. Medicare expenditures are increasing, and we can expect a general increase in the so-called "gerontological diseases". Full social security payments could be jeopardized.
International efforts are being made by the National Institute of Aging (NIA), the Italian Ministries of Universities and Research and similar funding agencies to focus on biological markers of aging to try to stem this potential tsunami effect. While research in this area is not new, stress now is on urgency to understand the various determinants of aging, standardize gerontological studies, monitor the impact of the various interactions on the rate of aging and find ways to determine the biological age of an individual as well as estimating the life expectancy of that individual. There is a slow shift toward prevention instead of curative research. Each researcher in this area appears to have a "favorite marker" for aging. We have seen lists that contain over forty potential markers including lung capacity, systolic blood pressure, cartilage telomere, fat-corrected forearm mineral content, lens density, serum cholesterol, lipofuscin in cerebral ganglia, dehydroepiandrosterone S, iliac trabecular bone volume percentage, peak filling rate etc. (See: Robert Weales article in J of Gerontology: Biological Sciences 2005;60A(1): 35-38)
In the year 1990, Mooradian wrote an article on biomarkers of aging in which he asked, "Do we know what to look for?" (J of Gerontol 1990;45:B183-186) How do we distinguish between age dependent diseases and the aging process itself? From the primate study initiated in 1987 at the National Institute on Aging (NIA), the following criteria for defining a biomarker of aging was promulgated: (1) significant cross-sectional correlation with age; (2) significant longitudinal change in the same direction as the cross-sectional correlation; (3) significant stability of individual differences over time. Here, they were looking at calorie reduction and prolonging life, not at the process of aging itself.
Researchers have identified certain aging "forces" in the body: oxidative damage (oxidative stress), reactive oxygen species (ROS), faulty anti-oxidation system, DNA damage and faulty DNA repair process, alterations in gene expression, mitochondrial damage, protein damage and decreased rate of protein turnover, damage to lipids, glycation, neuro-hormonal deregulation, genetic programming of lifespan potential, or a synergetic effect of all these factors. Still the hunt goes on. Below you will find reference to two cell regulators that may play a central part in aging and may have the seeds for designation as markers of aging.
During normal aging, there is a decline in the ability of various tissues to tolerate thermal, oxidative, pharmacological, nutritional and hypoxic/ischemic stress. There is diminished ability to make the molecular adjustments necessary to tolerate these different types of stress. These forms of stress are cumulative, with the effects of stress not manifesting itself until some sort of protective barrier is broken (coping balance tips in a negative way). Investigators indicate that a key regulator of cellular stress response in mammals, adosenine monophosphate-activated protein kinase (AMPK), may play a protective role in response to many types of stress. Lee and his group in a study of AMPK suggest that this kinase may be decreasing with age. He showed how the ability of tissues to tolerate hypoxic stress depends on AMPKs interaction with hypoxia-inducible factor-1 transcriptional activity and its target gene expression under hypoxic (decrease in oxygen) conditions. (See: Lee M., et al AMP-activated protein kinase activity is critical for hypoxia-inducible factor-1 transcriptional activity, and its target gene expression under hypoxic conditions in DU145 cells. J. Biol Chem; 278:39653-39661)
Another factor under consideration is dolichol, a polyisoprenic molecule, omnipresent in the lipid fraction of animal tissue. Dolichol appears to act as a free-radical scavenger in the cell membrane protecting polyunsaturated fatty acids from peroxidation. During human aging, the brain shows a progressive increase in levels of dolichol, while in neurodegenerative age-associated Alzheimers disease, the situation is reversed, with decreased levels of dolichol. (See: Bizzarri R. et al New perspectives for (S)-dolichol and (S)-nordolichol synthesis and biological functions. Biogerontology 2003;4: 353-363). A decrease in tissue dolichol may be the result of acute or chronic pathological conditions and a life-long deficiency of vitamin E and polyunsaturated fatty acids that results in increased oxidative stress and not dependent on age-dependent diseases.
Yet, during aging, for every increase, there seems to be a corresponding decrease in other factors as the various systems try to maintain a homeostasis. Thus, the increase in dolichol with aging is matched by a decrease in the levels of ubiquinone and a relatively unchanged concentration of cholesterol. This is an example of synergic reactions, making it difficult to isolate single biomarkers of aging.
Go Back to Article I of Articles on
Aging-Mortality risk factors
The Aging Process-Part II-Gender Difference
Go to Part III of Articles on Aging Cellular senescence
Go to Part IV of Articles on Aging Biological aging/health strategies
Go to Part V of Articles on Aging Arteriosclerosis
The Aging Process-Part VI-Aging in Males
The Aging Process-Part VII-Aging in Women
The Aging Process-Part VIII-Infectious Disease
Process of Aging-Part IX-DHEA
The Aging Process-Part X-Skin, Skeleton and Brain
The Aging Process:-Part XI-Apotosis and the Elderly
The Aging Process- Part XIII- Body Odors
FOR AN INFORMATIVE AND PERSONAL ARTICLE ON PRACTICAL SUGGESTIONS WHEN SELECTING A NURSING HOME SEE OUR ARTICLE "HOW TO SELECT A NURSING HOME".
by Harold Rubin, MS, ABD, CRC, Guest Lecturer
updated May 29, 2009
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