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Clinical biomarkers of aging

Database
Clinical aging biomarkers

Authors:

Andrjez Bartke, Luigi Ferrucci, Vincent Giampapa

History:

Scientists are trying to determine the most definite aging biomarkers. Thus, in the 80s of the last century, Olovnikov AM has noted the telomere shortening as a potential aging biomarker. Last years it was discovered a number of molecular biomarkers. For example, the scientists from King’s College London have first identified 22 molecular aging biomarkers in blood. And specialists from Stanford University School of Medicine have discovered some substances in blood of older mice. These substances caused the changes in brain of young animals, that are typical for the brain of old animals. The level of these substances increases with aging, and they appear to inhibit brain ability to produce the new neurones, which are important for memory formation and learning ability. The researchers from the University of Liverpool have created a new technique that will help other researchers to find genes, which are responsible for aging. They managed to identify genes in different tissues of humans and animals, which were exposed to multiple aging.

Example:

Scientists tend to make possible that fact when every person will be able to control aging process in their own organism. Currently about 100 possible aging biomarkers were proposed. In our country some clinical tests for some biomarkers are available: for example, the determination of biomarkers for some kinds of age-related and oncological diseases.

Description:

Aging biomarkers can be considered at four levels: physiological, cellular, molecular and chromosomal one. Physiological biomarkers include basic indicators of body functioning: eye and hearing examination, muscle mass, flexibility, aerobic endurance and others.

In order to determine the cellular aging biomarkers it should be taken a skin biopsy from the areas of skin, which seems to be in well condition. It is necessary to determine the quantity and quality of age-related changes in the structure of all skin layers: condition of epidermis and adipose glands, collagen content and skin elasticity.

At the molecular level it is possible to determine more definite aging biomarkers. To determine the molecular aging biomarkers it should be taken the analysis of key hormones: human growth hormone, thyroid hormone, Q10, insulin sensitivity, heat shock proteins, oncogene analysis, serum levels of antioxidants.

At the chromosomal level the aging biomarkers include determination of telomeres position and DNA degradation rate.
The scientists from the International Longevity Institute have developed the blood test, which will be able to monitor the DNA damage, and it will indicate the effect of anti-aging therapy at the DNA level.
Let’s talk more detail about some prospective aging biomarkers.

Human Growth Hormone

A possible aging biomarker is a growth hormone. It is well known that with aging the level of growth hormone decreases.
This decrease of growth hormone level is believed to be responsible for age-dependent accumulation of fat tissue, and loss of muscle tissue, as well as decrease of mineral content in bones. Therefore, it could be concluded that the reduced level of growth hormone leads to accelerated aging.

Thus, the members of Andrjez Bartke’s laboratory (Department of Physiology, Medical School, University of Southern Illinois) have obtained the data which show that the mice with impaired hypophysary function have longer lifespan, and overproduction of growth hormone lead to lifespan shortening.

AGE accumulation

AGE (glycation end products) can damage cells in different ways: functional impairment of proteins through modifications, cross-linking of proteins, induction of free radical formation, activation of immune response.
AGE accumulation was demonstrated on various kinds of tissues from patients suffered from diabetes. Moreover, the researchers from the Dr. Monnier’s laboratory (Cleveland, USA) have demonstrated that AGE accumulation could be used as a marker of early death of mice.

Increase of Interleukin-6

With aging the inflammatory cytokines are significantly activated. The examples are: Interleukin-6 (IL-6), tumour necrosis factor TNF-a, IL-1. At the same time the decrease of testosterone level in blood occurs.
Dr. Luigi Ferrucci (Department of Clinical Research Hospital in Harbour) has investigated a population of 473 elderly men and analyzed the interactions between level of testosterone and IL-6.

He has found out the dependence between the testosterone level and IL-6 receptor, which increases the activity of IL-6 cytokine. However, it was not found any relations with other inflammation markers. Meanwhile, other scientists have obtained the data about the relations between increased IL-6 expression with age-related cataracts; as well as relations between increase of mortality risk in the group of elderly men and increase of IL-6 levels.

Additions and Criticism:

Scientists have identified a number of aging biomarkers, but none of them are independent: only a set of markers can demonstrate a real aspect of aging. Separately none of biomarkers provide an exact forecast, mortality estimate or exactable lifespan, as well as a choice of the optimal therapeutic intervention to treat a particular disease. Therefore, researchers are trying to find more informative aging biomarkers to estimate the risk of disease development and to predict the disease outcome.

Publications:

  • McCarrey, Anna, et al. «Interleukin-6 (IL-6) is associated with longitudinal rates of cortical thinning." Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association 9.4 (2013): P307.
  • Imbert, Isabelle. «Biomarkers and aging." Biomarkers in medicine 8.5 (2014): 621–623.
  • Zhang, Wei-Guang, et al. «Select aging biomarkers based on telomere length and chronological age to build a biological age equation." Age 36.3 (2014): 1201–1211.
  • Mishur, Robert J., and Shane L. Rea. «Applications of mass spectrometry to metabolomics and metabonomics: Detection of biomarkers of aging and of age‐related diseases." Mass spectrometry reviews 31.1 (2012): 70–95.