Telomere length: where your real age is hidden!

Written by on September 9th, 2013. Posted in Articles

In 2009 three American scientists—Elizabeth Blackburn, Carol Greider and Jack Szostak—shared the Nobel prize for in Medicine for their research and discoveries of how chromosomes are protected by telomeres and the enzyme telomerase. These findings were very promising for prevention of age-related diseases and achievement of a long and healthy live. Recently related discoveries have expanded not only scientists’ interest but also that of common people who are looking to find the secrets of longevity. We have known for quite few years the protective role of telomeres and their association with cellular aging, however the current insights into the specific molecular mechanisms of telomeres function made scientific community speaking even for the ability to reverse aging process. But is that possible and to what extend?
Telomeres: “the tips at the end of shoelaces”
DNA is our genetic blueprint, encoding the genetic instructions necessary for the function and development our cells and whole organism. Our genetic material defines every aspect of our life, right from the definition of our physical features to our “gifts”, our disadvantages and our susceptibility to disease. And because of its crucial role, it is of great significance for the genome to be protected from a numerous of factors “threatening” its structure and stability. One of the protective mechanisms is lying in presence of telomeres.
Telomeres are a complex of specific and repeated DNA sequence (TTAGGG in humans) with proteins (the shelterin complex) lying at the end of each chromosome (in both chromatids). This structure despite it does not contain genetic information it is essential to protect genome from degradation, unnecessary recombination, repair, and fusion between neighboring chromosomes. During cell division, DNA is replicated by DNA polymerase but this enzyme does not have the ability to replicate the very end sequences of telomeres (known as the “end-replication problem”). Thus after each replication cycle the telomeres are shortened. It is fairly estimated that with each cell cycle between 50 and 200 nucleotides are lost. The enzyme complex of telomerase is responsible to add telomeric sequences at the end of chromosomes. However its activity is very low or even lost in most somatic cells so it cannot compensate adequately the lost sequence (telomerase activity is preserved for obvious reasons in germline and stem cells. Also telomerase is thought to be reactivated in high levels in cancer cells which are immortalized).
When telomere length reaches a threshold, the cell becomes unable to replicate, entering a phase of cellular growth arrest termed replicative senescence. On average senescence occurs after 50 divisions (Hayflick limit). The senescent phase may then progress to cell death or apoptosis, and consequently to what we see and call “aging” (1,2,3).

Telomeres length variation: the secret of our biological age and its association with disease

Telomere ends are estimated at an average of 15000bp at birth and 5000bp at the time of death. However an important variation is observed among individuals even at birth which is influenced by race and gender (e.g. women have longer telomeres than men, and African-Americans have longer telomeres than Caucasians and Indians) (3). But the striking discoveries that come daily into the light are the associations of telomere length (TL) with pace of aging and certain age-related diseases. Studies have shown that shorter telomere length is associated with cardiovascular disease (heart failure, atherosclerosis, heart attack, hypertension) (3,4,5), diabetes (6,7) and cancer (2,8). Moreover there is evidence that shorter telomeres may also relate to reduced Bone Mineral Density and osteoporosis (9,10), inflammatory diseases (2,11), dementia and even mood disorders (12,13).
And since our physical appearance is the mirror of our age, premature skin aging (with early formation of wrinkles, skin slacking, etc.) seems also to be associated with telomere length (14,15).

On the other hand longer telomeres have been associated with healthier living years. Despite it would be unorthodox to state that TL predicts our lifespan- since life expectancy is influenced by a numerous of factors- it is at least fair to say that longer telomeres are a strong indicator of our biological age, representing an internal “biological clock” (2,16).

Telomere length is dynamic and affected significantly by the oxidative DNA damage induced by environmental risk factors. In fact the normal phenomenon of telomere shortening due to the “end-replication problem” is small and constant in each cell. On the other hand the shortening caused by oxidative stress is proportional to telomere length, as longer telomeres are larger targets for free radicals. Thus environmental factors (lifestyle habits, stress, smoking and many others) inducing oxidative DNA damage have shown to cause important increase of TL shortening (2,7,17).

What is the benefit of knowing our biological age?

Until recently testing of telomere length was only carried out for scientific research studies. However the development of laboratory technology and protocols, the recent strong evidence of TL association with health status and the interest of general population to preventive medicine, has led to the first “telomere tests” available in market. These tests usually focus on measuring the average telomere length in specific cell populations. The data derived is then compared to the average lengths in the general population of the same age. Thus estimation is made whether an individual’s biological is relatively below, above or equal to his/her chronological age. Such tests are not diagnostic, but have an important predictive value (18).

The interesting and most important benefit of knowing our biological age lies on the dynamic nature of telomeres. It has been shown in extensive research studies that our lifestyle affects significantly the rate of telomere shortening. Among the several factors we could note the most important being: diet, physical activity, obesity, smoking and stress. In general, people who follow a healthy diet (low fat, rich in fibers, in fruits and vegetables, in ω-3 fatty acids, etc.), have a normal weight and waist-hip circumference ration, are physical active, avoid smoking and manage stress factors, tend to have importantly longer telomeres. Moreover there is evidence for certain nutritional supplementation that could help avoid extended and premature telomeres shortening (19-27).

Data derived from telomere testing when evaluated by specialized health professionals will provide us with vital information on which lifestyle changes can expand our healthy living years by delaying aging process and preventing earlier onset of age-related diseases. Despite we cannot “turn back time” we have currently the tools to “read our real age written in our cells” and take the appropriate corrective actions to delay the pace of aging –from skin to whole body function-.


1. Njajou OT, Hsueh WC, Blackburn EH, Newman AB, Wu SH, Li R et al.: Association between telomere length, specific causes of death, and years of healthy life in health, aging, and body composition, a population-based cohort study. J Gerontol A Biol Sci Med Sci. (2009); 64(8):860-4.
2. Shammas MA.: Telomeres, lifestyle, cancer, and aging. Curr Opin Clin Nutr Metab Care. (2011); 14(1):28-34.
3. Sajidah Khan, Datshana P Naidoo and Anil A Chuturgoon: Telomeres and atherosclerosis. Cardiovasc J Afr. (2012); 23(10): 563-571.
4. Chimenti C, Kajstura J, Torella D, Urbanek K, Heleniak H, Colussi C et al.: Senescence and death of primitive cells and myocytes lead to premature cardiac aging and heart failure. Circ Res. (2003); 3: 93(7):604-13.
5. Gleichmann U, Gleichmann US, Gleichmann S.: From cardiovascular prevention to anti-aging medicine: influence on telomere and cell aging. Dtsch Med Wochenschr. (2011) ;136(38):1913-6.
6. Kuhlow D, Florian S, von Figura G, Weimer S, Schulz N, Petzke KJ, Zarse K et al.: Telomerase deficiency impairs glucose metabolism and insulin secretion. Aging (Albany NY) (2010); 2(10):650-8.
7. Sampson MJ, Winterbone MS, Hughes JC, et al.: Monocyte telomere shortening and oxidative DNA damage in type 2 diabetes. Diabetes Care. (2006); 29:283–289.
8. Donate LE, Blasco MA.: Telomeres in cancer and ageing. Philos Trans R Soc Lond B Biol Sci. (2011); 366(1561):76-84.
9. Valdes AM, Richards JB, Gardner JP, et al.: Telomere length in leukocytes correlates with bone mineral density and is shorter in women with osteoporosis. Osteoporos Int. (2007); 18: 1203–1210.
10. Bekaert S, Van Pottelbergh I, De Meyer T, Zmierczak H, Kaufman JM, Van Oostveldt P, Goemaere S. : Telomere length versus hormonal and bone mineral status in healthy elderly men. Mech Ageing Dev. (2005); 126(10):1115-22.
11. Steffens JP, Masi S, D’Aiuto F, Spolidorio LC.: Telomere length and its relationship with chronic diseases – New perspectives for periodontal research. Arch Oral Biol. (2012); pii: S0003-9969(12)00330-5. doi: 10.1016/j.archoralbio.2012.09.009.
12. Tim De Meyer: Telomere Length Integrates Psychological Factors in the Successful Aging Story, But What About the Biology? Psychosomatic Medicine September (2011); 73(7): 524-527.
13. Ma SL, Lau ES, Suen EW, Lam LC, Leung PC, Woo J, Tang NL.: Telomere length and cognitive function in southern Chinese community-dwelling male elders. Age Ageing (2013); 42(4):450-455.
14. Buckingham EM, Klingelhutz AJ. The role of telomeres in the ageing of human skin. Exp Dermatol. ( 2011) ;20(4):297-302.
15. Krunic D, Moshir S, Greulich-Bode KM, Figueroa R, Cerezo A, Stammer H, et al.: Tissue context-activated telomerase in human epidermis correlates with little age-dependent telomere loss. Biochim Biophys Acta. (2009); 1792(4):297-308.
16. Njajou OT, Hsueh WC, Blackburn EH, Newman AB, Wu SH, Li R et al.: Association between telomere length, specific causes of death, and years of healthy life in health, aging, and body composition, a population-based cohort study. J Gerontol A Biol Sci Med Sci. (2009); 64(8):860-4.
17. Wolkowitz OM, Mellon SH, Epel ES, Lin J, Dhabhar FS, et al. Leukocyte Telomere Length in Major Depression: Correlations with Chronicity, Inflammation and Oxidative Stress – Preliminary Findings. PLoS ONE (2011); 6(3): e17837. doi:10.1371/journal.pone.0017837
18. Howard Wolinsky: Testing time for telomeres. EMBO Rep.(2011); 12(9): 897-900.
19. Aedín Cassidy, Immaculata De Vivo, Yan Liu, Jiali Han, Jennifer Prescott et al.: Associations between diet, lifestyle factors, and telomere length in women. Am J Clin Nutr 2010;91:1273–80.
20. García-Calzón S, Gea A, Razquin C, Corella D, Lamuela-Raventós RM, Martínez JA, Martínez-González MA et al.: Longitudinal association of telomere length and obesity indices in an intervention study with a Mediterranean diet: the PREDIMED-NAVARRA trial. Int J Obes (Lond). (2013); doi: 10.1038/ijo.2013.68.
21. Østhus IBØ, Sgura A, Berardinelli F, Alsnes IV, Brønstad E, et al. (2012) Telomere Length and Long-Term Endurance Exercise: Does Exercise Training Affect Biological Age? A Pilot Study. PLoS ONE 7(12): e52769. doi:10.1371/journal.pone.0052769.
22. Puterman E, Lin J, Blackburn E, O’Donovan A, Adler N, et al. (2010) The Power of Exercise: Buffering the Effect of Chronic Stress on Telomere Length. PLoS ONE 5(5): e10837. doi:10.1371/journal.pone.0010837.
23. Ornish D, Lin J, Daubenmier J, Weidner G, Epel E, Kemp C et al.: Increased telomerase activity and comprehensive lifestyle changes: a pilot study. Lancet Oncol. (2008); 9(11):1048-57.
24. Valdes AM, Andrew T, Gardner JP, Kimura M, Oelsner E, Cherkas LF et al.: Obesity, cigarette smoking, and telomere length in women. Lancet. (2005); 366(9486):662-4.
25. Liang G, Schernhammer E, Qi L, Gao X, De Vivo I, et al. (2011) Associations between Rotating Night Shifts, Sleep Duration, and Telomere Length in Women. PLoS ONE 6(8): e23462. doi:10.1371/journal.pone.0023462.
26. McGrath M, Wong JY, Michaud D, Hunter DJ, De Vivo I.: Telomere length, cigarette smoking, and bladder cancer risk in men and women. Cancer Epidemiol Biomarkers Prev. (2007) ;16(4):815-9.
27. Zannolli R, Mohn A, Buoni S, Pietrobelli A, Messina M, Chiarelli F, Miracco C.: Telomere length and obesity. Acta Paediatr. (2008); 97(7):952-4.

Autoimmune diseases: How can you protect your body from itself?

Written by on September 12th, 2012. Posted in Articles

Autoimmune disorders include an extensive number of medical conditions with clinical symptoms that may vary from mild to severe. Despite autoimmune diseases affect variable tissues, organs or systems; the common characteristic of such conditions is that the body inappropriately attacks its own cells.

Immune system is highly complex, with several types of cells and organs cooperating to ensure that we are adequately protected from harmful “foreign” substances, called antigens, like bacteria, viruses, toxins, cancer cells, and blood or tissues from another person or species. Antibodies and other crucial proteins are produced to fight and eliminate such “invaders”. Inflammation is the response of the organism to remove the antigens and to initiate the healing process. We have all experienced common symptoms of local inflammation like redness, swelling, pain. However in cases of autoimmune disorders our immune system incorrectly recognizes its own cells as antigens and attacks them, triggering the inflammatory cascade and other biochemical processes that damage its own tissues.

Autoimmune conditions are included in the complex multi-factorial diseases. Both genetic make up and environmental factors contribute synergistically to manifestation of such disorders. Currently scientific research has revealed several variations in genes which predispose to inappropriate immune response or excessive inflammation.
Certain polymorphisms in genes involved in immune response like HLA-DRB1 [1,2,3], STAT4 [4,5], TRAF1-C5 [6,7] , have been associated with increased risk for Rheumatoid Arthritis; a condition characterized from pain and swelling in joints leading even to joints deformity overtime. Another relatively common autoimmune disease affecting joints in spine, as well as tendons and ligaments around bones is Anklylosing Spondylitis. Patients suffer from back pain that varies from impermanent to spinal stiffness overtime. Certain genetic variants predispose individuals to this condition; with the presence of HLA-B27 [being the most important genetic risk factor (around 80% of patients share this type of genetic polymorphism) [8,9,10]. Multiple sclerosis, a serious neurological disorder, is caused by inflammation due to inappropriate attack of immune system to the nerve cells. Severe damage to the myelin sheath – a protecting covering of nerve cells- results to decrease of nerve signals. A patient may experience almost any neurological symptom; loss of sensation, muscle weakness, coordination and balance (ataxia) difficulties, visual problems, fatigue, acute or chronic pain, and bladder and bowel difficulties. Again genetic make up is involved in manifestation of the disease, since genetic variants in IL7R [ 11,12,13] and HLA-DRA [12,14] have been associated with higher risk. Psoriasis, another disease in the extensive list of autoimmune conditions, affects the skin by accelerating abnormally the skin cells cycle. The characteristic silvery white scales are among the most common signs of the disease (other symptoms are red lesions in face and arms, psoriatic arthritis and neuropathy). Polymorphisms in genes HLA-C, IL12B, IL23R [18,16,17,18,19] have been associated with defects in immune response and increased risk for psoriasis.

Despite the complex genetic mechanisms behind the scenes, the role of environmental factors in autoimmune disorders should not be in anyway underestimated. Primarily dietary habits are crucial for appropriate function of the immune system. In particular a diet that is rich in Vitamins A, B complex, C, D, E, (available in fresh colored fruits and green leafy vegetables) as well as a diet rich in poly-unsaturated fatty acids (available from oily fish, walnuts, almonds, peanuts, etc.) enhances our body defense and eliminates inflammation. Physical exercise has also a significant role in regulation of immune function and inflammation. On the other hand a diet that is rich in trans-fats (found primarily in processed foods), smoking, stress and sedentary lifestyle can all have significantly harmful effects in developing an autoimmune condition, especially in case an individual has already a genetic profile that is associated with higher risk [20,21,22,23].

Autoimmune conditions – especially when not diagnosed early- can have detrimental effects in patients and close friends and families. They reduce importantly the quality of life with chronic surveillance and management being necessary. Despite we cannot change our genetic make up, we can take all the effective measures to reduce our genetic risk and even prevent the development of an auto-immune disease. Nowadays it is feasible to know our personal genetic profile by taking a simple DNA test that will reveal if we carry the so far known genetic variants associated with autoimmune disorders. With scientific consultation by specialized health professionals (clinicians, dieticians, etc.) an individual with higher genetic risk for such conditions can be guided appropriately with preventive lifestyle interventions and clinical surveillance recommendations.


1. Weyand CM, Xie C, Goronzy JJ. Homozygosity for the HLA-DRB1 allele selects for extraarticular manifestations in rheumatoid arthritis. J Clin Invest. 1992;89(6):2033-9.
2. Roudier J. HLA-DRB1 genes and extraarticular rheumatoid arthritis. Arthritis Res Ther. 2006;8(1):103.
3. Gorman JD, David-Vaudey E, Pai M, Lum RF, Criswell LA. Particular HLA-DRB1 shared epitope genotypes are strongly associated with rheumatoid vasculitis. Arthritis Rheum. 2004;50(11):3476-84.
4. Liang YL, Wu H, Shen X, et al. Association of STAT4 rs7574865 polymorphism with autoimmune diseases: a meta-analysis. Mol Biol Rep. 2012;39(9):8873-82.
5. Orozco G, Alizadeh BZ, Delgado-Vega AM, et al. Association of STAT4 with rheumatoid arthritis: a replication study in three European populations. Arthritis Rheum. 2008;58(7):1974-80.
6. Plenge RM, Seielstad M, Padyukov L, et al. TRAF1-C5 as a risk locus for rheumatoid arthritis–a genomewide study. N Engl J Med. 2007;357(12):1199-209.
7. Zervou MI, Sidiropoulos P, Petraki E, et al. Association of a TRAF1 and a STAT4 gene polymorphism with increased risk for rheumatoid arthritis in a genetically homogeneous population. Hum Immunol. 2008;69(9):567-71.
8. Seipp MT, Erali M, Wies RL, Wittwer C. HLA-B27 typing: evaluation of an allele-specific PCR melting assay and two flow cytometric antigen assays. Cytometry B Clin Cytom. 2005;63(1):10-5.
9. Sayer DC, Cassell HS, Christiansen FT. HLA-B*27 typing by sequence specific amplification without DNA extraction. Mol Pathol. 1999;52(5):300-1.
10. Rahman P, Inman RD, Gladman DD, Reeve JP, Peddle L, Maksymowych WP. Association of interleukin-23 receptor variants with ankylosing spondylitis. Arthritis Rheum. 2008 Apr;58(4):1020-5.
11. Zhang R, Duan L, Jiang Y, et al. Association between the IL7R T244I polymorphism and multiple sclerosis: a meta-analysis. Mol Biol Rep. 2011;38(8):5079-84.
12. Lander ES, Daly MJ, De Jager PL, et al. Risk alleles for multiple sclerosis identified by a genomewide study. N Engl J Med. 2007;357(9):851-62.
13. Alcina A, Fedetz M, Ndagire D, Fernández O, Leyva L, Guerrero M, Arnal C, Delgado C, Matesanz F. The T244I variant of the interleukin-7 receptor-alpha gene and multiple sclerosis. Tissue Antigens. 2008;72(2):158-61.
14. Rasmussen HB, Kelly MA, Clausen J. Additive effect of the HLA-DR15 haplotype on susceptibility to multiple sclerosis. Mult Scler. 2001;7(2):91-3.
15. Liu Y, Helms C, Liao W, et al. A genome-wide association study of psoriasis and psoriatic arthritis identifies new disease loci. PLoS Genet. 2008;4(3):e1000041.
16. Filer C, Ho P, Smith RL, et al. Investigation of association of the IL12B and IL23R genes with psoriatic arthritis. Arthritis Rheum. 2008;58(12):3705-9.
17. Cargill M, Schrodi SJ, Chang M, et al. A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. Am J Hum Genet. 2007;80(2):273-90.
18. Nair RP, Duffin KC, Helms C, et al. Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nat Genet. 2009;41(2):199-204.
19. Nair RP, Ruether A, Stuart PE, et al. Polymorphisms of the IL12B and IL23R genes are associated with psoriasis. J Invest Dermatol. 2008;128(7):1653-61.
20. Fernandes G. Dietary lipids and risk of autoimmune disease. Clin Immunol Immunopathol. 1994;72(2):193-7.
21. Costenbader KH, Karlson EW. Cigarette smoking and autoimmune disease: what can we learn from epidemiology? Lupus. 2006;15(11):737-45.
22. Simopoulos AP. Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr. 2002 Dec;21(6):495-505.
23. Shephard RJ, Shek PN. Autoimmune disorders, physical activity, and training, with particular reference to rheumatoid arthritis. Exerc Immunol Rev. 1997;3:53-67.

Predictive Genomics for Alzheimer’s disease

Written by on May 2nd, 2012. Posted in Articles

Alzheimer’s disease (AD) is an irreversible neurodegenerative disorder. Being the most common type of dementia, 35.6 million people worldwide were affected in 2010 and the number is estimated to double every 20 years. It affects primarily people above the age of 65, with a low rate of the patients being younger.  The condition is characterized by loss of neurons and synapses in the brain, caused by development of amyloid plaques and neurofibrillary tangles.

Currently there is no cure for Alzheimer’s disease, and management of patients is significantly costly, especially in Europe and the United States. Moreover due to the nature of the disease, psychological burden for people close to patients is a serious effect. Thus scientist’s efforts have been for years focused on understanding the roots of the condition that could lead to an effective treatment and/or even prevention (1,2).

Genetics research has enlightened over the past few years the role of genes in manifestation of the condition. Early onset of the condition (hereditary-familial form) is caused by rare, fully penetrant mutations in three different genes. However for the vast majority of cases (90%), the exact cause of the disease on a molecular level remains unclear (3).

The most recent research evidence leads scientists to list Alzheimer’s disease among the multi-factorial conditions, where both genetic and environmental factors playing a crucial role. Genome-wide association studies (GWAS) of late-onset Alzheimer disease have consistently observed strong association with polymorphisms (SNPs) in gene APOE (4,5,6). Specifically it has been shown that carriers of the allele e4 (resulting from a haplotype of two SNPs in APOE), deal with significantly increased risk for Alzheimer’s. APOE is the major cholesterol carrier in brain and the presence of the allele e4 is shown to disrupt cholesterol regulation and β-amyloid degradation. This results to β-amyloid accumulation in brain supporting the most established theory for β-amyloid deposits being the main cause of the condition.  However this gene variant seems to explain approximately 50% of the cases. Strong association was also found for a SNP in APOC1, which modulates the function of the APOE gene (7,8). Such evidence suggested a strong link between cholesterol regulatory pathway and Alzheimer’s condition. Other genetic variants have been also implicated in Alzheimer’s disease, which act rather in a more synergistic way, conferring a risk that could be considered important when combined with the presence of APOE4 allele.

Moreover increased plasma homocysteine levels are implicated in the disorder. MTHFD1L encodes an enzyme in one of the steps for homocysteine conversion to methionine. A gene variant in MTHFD1L has been associated with increased risk for Alzheimer’s disease, indicating that an additional molecular pathway involved in Alzheimer’s disease is homocysteine metabolism (9).

Assessing an individual’s genetic profile by testing for the polymorphisms known to affect risk for AD, could have a key role in prevention of the disorder. An estimated increased genetic risk -compared to the general population- will motivate individuals to get advice from health professionals for appropriate and effective guidelines. Based on the DNA results, certain nutritional recommendations that focus mainly on low saturated fat diet and low sugar intake can be importantly beneficial for brain function. Regular check up of cholesterol and homocysteine levels will help individuals at risk for better and efficient monitoring of those substances which are implicated in AD manifestation. Moreover regular physical exercise has shown tremendous benefits in AD prevention. The most stunning results however can be achieved with brain gymnastics (reading, crossword puzzles, board games, etc.) according to Neurologists, since mental practice can reduce up to 70% the risk for AD. The future of preventive rather than invasive medicine is very promising; identifying the personalized risk of individuals allows the implement of early and effective adjustments that address to personal genetic needs.


1. National Institutes of Health. National Institute on Aging. Alzheimer’s diseases Education and Referral Center. Alzheimer’s Disease Fact Sheet. Available at (Accessed on: April 23, 2012).

2. Alzheimer’s Disease International. Dementia statistics. Available at (Accessed on April 20, 2012).

3. Stephen C. Waring, Roger N. Rosenberg. Genome-Wide Association Studies in Alzheimer Disease. Arch Neurol 2008;65(3):329-334.

4. W J Strittmatter, A M Saunders, D Schmechel, M Pericak-Vance, J Enghild, G S Salvesen, and A D Roses. Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci 1993; 90: 1977-1981.

5. Eden R Martin, Eric H. Lai, John R. Gilbert, Allison R. Rogala, A. J. Afshari, John Riley, et al. SNPing Away at Complex Diseases: Analysis of Single-Nucleotide Polymorphisms around APOE in Alzheimer. Am J  Hum  Genet 2000; 67:383–394.

6. Andrew Grupe, Richard Abraham, Yonghong Li, Charles Rowland, Paul Hollingworth, Angharad Morgan, et al. Evidence for novel susceptibility genes for late-onset Alzheimer’s disease from a genome-wide association study of putative functional variants. Hum Mol Genet 2007; 16 (8): 865-873.

7. Li H, Wetten S, Li L, St Jean PL, Upmanyu R, Surh L, Hosford D, et al. Candidate single-nucleotide polymorphisms from a genomewide association study of Alzheimer disease. Arch Neurol 2008;65(1):45-53.

8. Bertram L, Lange C, Mullin K, Parkinson M, Hsiao M, Hogan MF, et al. Genome-wide association analysis reveals putative Alzheimer’s disease susceptibility loci in addition to APOE. Am J Hum Genet. 2008;83(5):623-32.

9. Naj AC, Beecham GW, Martin ER, Gallins PJ, Powell EH, Konidari I, et al. Dementia revealed: novel chromosome 6 locus for late-onset Alzheimer disease provides genetic evidence for folate-pathway abnormalities. PLoS Genet 2010; 6(9). pii: e1001130.

10. Alzheimer’s Research & Prevention Foundation. Alzheimer’s Prevention. Available at (Accessed on: April 23, 2012).

Defenses against Skin Aging process from the inside out

Written by on September 8th, 2011. Posted in Articles

Aging is a normal process of the cells and the human body in general. As we get older our natural defenses are reduced, free radicals are less deactivated, resulting to internal damages. Cells’ proliferation rate is reduced, and cells’ death increases, something obvious in our skin appearance. A similar process occurs inside our body, and several conditions threat our health.

In many cases aging begins to show its signs earlier in life than expected. This is observed primarily in our skin condition, as this outer layer of epidermis is the most exposed to several environmental pollutants. Other factors, like unhealthy nutrition poor in vitamins, smoking, sunlight, and air pollution contribute significantly to premature forming of wrinkles and skin slacking.

However we often come across people who -in contrast to their old age- show a very good skin health, maintaining a youthful appearance. This can be -to an extent- the result of the cosmetic products available nowadays, which contain important ingredients for the skin protection and rejuvenation. But this alone is not sufficient to lead to a youthful skin looking, as genes play also a significant role.

The human body has numerous of mechanisms to ensure its survival. Anti-oxidation and Detoxification systems are of the most important, protecting our cells from free radicals. These reactive oxygen species are produced either as natural by-products from several functions in the cells, or come from toxins that the body, like environmental pollutants and drugs’ compounds. Free radicals can cause a condition known as oxidative stress, when their production exceeds their deactivation. This harms seriously the cells, causing significant damage to its genetic material, DNA. And as DNA contains the necessary information for all the normal functions of the body, such harmful effects are responsible for many diseases, from cancer to neurological disorders (1,2).

Genetic research over the past years has revealed several gene mutations which can cause defects in processes of anti-oxidation and detoxification, like GSTT1, GPX1, CAT and several others (3,4,5,6). People carrying such mutations are less protected to skin cells’ damages and more susceptible to premature skin aging.

Moreover genes like MTHFR, MTR and MTRR are involved in folic acid metabolism. Mutations in such genes can results to serious defects in DNA synthesis and repair, causing earlier cells’ death and again earlier development of skin aging (7,8).

Collagen is a structural protein of the skin that gives the smoothness and youth to this layer of epidermis. As we grow older, collagen production is importantly reduced in contrast to collagen breakdown which is increased. Genetic background is also very important for the age of skin aging onset, as gene mutations involved in collagen synthesis and/or breakdown may lead to early skin slacking and other signs of skin aging (9,10).

Increased exposure to sunlight can also harm seriously the health of skin cells. UV irradiation causes DNA damages that lead to early formation of skin wrinkles, freckles and even skin cancer. Some people however are more vulnerable to such harmful effects of the sun than the general population due to their genetic profile.

Nowadays that we can be aware -at some important extent- of the roots of the aging process, people can be more properly guided to avoid early symptoms of aging. One aspect is the use of the appropriate cosmetic products (creams that purify the skin and clean from toxins, and sunscreens with increased SPF) that address to their personal needs as indicated by their genetic profile.

Furthermore individuals can follow what is called a personal Nutritional Plan based on their genetic needs. Based on their genetic profile they can be provided with appropriate nutritional recommendations (e.g. for increased intake of fresh fruits and vegetables) or guidance for supplements with certain bioactive compounds. Thus they can enhance the battle against aging, from the inside out, targeting to internal systems of the body.

Type 2 Diabetes: when genes make sugar taste bitter

Written by on September 8th, 2011. Posted in Articles

Diabetes Mellitus belongs to the most common medical conditions worldwide, showing importantly increasing rates. Data from the WHO (World Health Organization) are far from being pessimistic for the future as more than 400 millions of people around the world are expected to suffer from the condition in the next 2 decades (1).

When we eat, glucose (commonly known as sugar) coming from food metabolism is released in blood circulation and is ready to be used from the body, as it is the most important energy source for the cells. Insulin – a hormone produced in pancreas and released in blood circulation- is responsible for the absorption of glucose from fat, muscle and liver cells. Diabetes occurs when either insulin production from pancreas is not sufficient or insulin is not effectively used by the body. Consequently glucose levels in blood are excessively increased with serious health implications. Cardiovascular disease, nephropathy, foot damage are some of the complications of diabetes, which lead to death millions of people annually.

There are two types of diabetes mellitus. Type 1 is due to defective insulin production and requires daily administration of insulin. The cause has not been yet clear, but genes play a dominant role. Usually symptoms begin from childhood and prevention measures seem to have only limited effects.

Type 2 Diabetes is the most common form of diabetes, with 90% of cases being characterized as such. It occurs either because cells become resistant to insulin signaling (insulin resistance) resulting to a not properly absorption of the glucose, or because pancreas stops to produce/release adequate insulin. Environmental factors, like nutritional habits, being overweight and following a sedentary lifestyle play a significant role in development of the condition. However genetic background of an individual can also increase his/her risk to Type 2 Diabetes (1,2).

DNA is our genetic blueprint and despite 99.9% of it is identical among people, the remaining 0.1% defines our individuality: from physical characteristics to disease susceptibility. These tiny variants are called polymorphisms/mutations and scientists in the fields of Medical Genetics and Predictive Genomics have focused to identify their effects primarily in health. Knowing the roots of the problem leads to a better understanding of the causing mechanisms and thus to more efficient preventive measures.

Genetic composition is a strong factor for predicting an individual’s risk to Type 2 Diabetes. Scientists have over the past years identified several polymorphisms in genes associated with higher risk for Type 2 diabetes. Mutations in genes known to affect the sensitivity / response of cells to insulin (like PPAR-γ, CDKAL1, HHEX, IGF2BP2, SLC630A8) have been found to increase the risk for a person who carries them (3,4,5,6,7).  Moreover – and a bit unexpected- genes involved to inflammatory conditions seem to have a strong effect on blood glucose levels. Certain variants in genes like TNF-a, IL-6 (8,9,10,11) have shown to affect the risk for this metabolic disorder. More data will be definitely available in the future, contributing even more to the efforts of scientists involved in Medical Genetics.

The ultimate purpose of Predictive Genomics is to pave the way for the appropriate, early, and as much as possible individualized and personalized actions to help individuals to reduce disease risks. This also applies to the case of Type 2 Diabetes test, since – as stated before – environmental factors can importantly alter a person’s risk. In case an individual is assessed with a higher risk compared to the general population appropriate Medical, Pharmacological, Nutritional and Environmental pre-symptomatic measures –addressing to the personal genetic risk of the individual- and therapies can be implemented for prevention or delay of disease onset.

Optimal Bones Health: A long-standing process

Written by on September 8th, 2011. Posted in Articles

Bones have crucial and multiple roles: support and protect the organs of the body, produce red and white blood cells, store minerals. Therefore bone health is very important to ensure the general normal function of the body. However as we get older, bones tissue begins to lose some of its abilities to support sufficiently the body, resulting to health problems.

Osteoporosis is a common condition, characterized by low bone mineral density-BMD.  The bones resorption exceeds bone formation, resulting to progressive loss of bone mass. Bone tissue structure deteriorates and individuals deal with increased risk for fractures. This condition is observed more often in women, especially after menopause, due to estrogen deficiency. Also it can result from other exogenous reasons, like under-nutrition and use of corticosteroids.

Fracture rates depend importantly on lifestyle factors. Sufficient intake of Calcium and Vitamin D can protect significantly from acceleration of osteoporosis and reduce the risk for serious fracture. In fact, such dietary factors play a crucial role from the very early time in a person’s life. Especially for girls, who acquire most of their skeletal mass by their 20’s, it is crucial to supply their bodies with sufficient nutrients even from childhood.

Moreover physical activity has been proved to be very beneficial in preventing osteoporosis. Regular exercise that includes weight bearing activities (like walking, basketball, jogging, dancing and weight lifting) improves muscles and bones structure and better body support.  A proper plan for physical activity should be again -like the nutritional one- followed from early in life, to ensure optimal bone health in adulthood (1,2).

However the risk for osteoporosis is not only a matter of lifestyle. Genetic research has shown that some people deal with increased risk compared to the general population, due to their genetic background. Despite we all share approximately 99.9% of common genetic material, there are DNA variants in the genes, which can affect importantly the susceptibility to health conditions.

VDR is a protein involved in Vitamin D and calcium absorption, having an important role in proper bones structure and function. However certain DNA changes in the gene encoding for this protein have been associated with defects in the normal function of VDR and thus increased risk for bones problems (3,4,5,6).

CTR which binds to calcitonin, also functions to ensure calcium homeostasis, particularly with regard to bone metabolism. During the normal process of bone turnover, a microscopic amount of bone is removed (bone resorption) and then replaced by new tissue. Scientists have found that when CTR variants are present in the gene an individual may deal with problems in calcium homeostasis and thus increased risk for osteoporosis (7,8,9).

In skeletal homeostastis LPR5 protein has also an important role. Several disorders related to bone density (like osteoporosis) are caused by mutations in the gene that encodes this protein (10,11,12).

With all the major steps made the past few years in Genetics field, people are able to know their genetic profile (regarding the mentioned and other mutations) and if their genes increase their susceptibility to osteoporosis.

Such knowledge can have tremendous results in prevention of the condition. Personalized nutritional and general lifestyle consultation is nowadays more feasible than ever, since it is based not only to clinical and biochemical data (“what we see”) but also on the precious (“hidden”) information that genes provide. Thus the effectiveness of prophylactic measures can increase substantially.  Moreover appropriate medical and nutritional advice can be implemented as earlier as possible, without waiting for the first clinical symptoms. But even in cases the conditions develops, knowing the genetic background will provide health professionals with important information regarding the roots of the problem, giving the option for therapies with more effective results.

Obesity: is it an inevitable hereditary disorder?

Written by on September 8th, 2011. Posted in Articles

Obesity has increased dramatically over the past years -mostly in industrialized but also in developing countries- and is classified by the WHO (World Health Organization) as epidemic. With major consequences in health, public health, economy and society, an important effort has been made by scientists to discover the cause for this phenomenon (1).

In order to classify individuals as overweight or obese, a measurement called BMI (Body Mass Index) is used. BMI is the individual’s body weight (kg) divided by the square of the height (m). A person with a BMI between 25 and 30 is considered as overweight, whereas one who has exceeded 30 is considered as obese. There are also other markers taken into account, like fat accumulation versus muscle mass, but BMI is the most commonly and well accepted measurement to distinguish people who exceed the normal weight.

Being overweight or obese does not only affect the self-esteem of an individual, but has serious implications for the health. Importantly increased risk for cardiovascular disease, diabetes, hypertension, obstructive sleep apnea, even certain types of cancer.

Contrary to conventional wisdom, being overweight or obese is not just because of overeating. It is the result of many factors, as obesity is nowadays characterized as a multi-factorial, polygenic disorder. What and how we eat is determined by a numerous of factors, not all of them being obvious. Scientific research has revealed that apart from environmental factors, genetic background plays also an important role, as certain gene mutations can make some people more susceptible to obesity.

A group of such mutations are found in genes that are involved in appetite regulation, feeding behavior and metabolism. It is not surprising that most of these genes produce proteins in hypothalamous, the portion of brain that regulates hanger and others that are produced in adipose (fat) tissue.

FTO (2,3,4) is an example of such genes, as mutations can cause defects in energy intake regulation and satiety. In simple words a person who carries such mutations, may be unable to control his/her appetite, and know when he/she had enough of food.

ACDC (5,6) gene produces a hormone in adipose tissue involved in fatty acid breakdown and glucose regulation. Mutations in this gene have shown to cause increased fat storage. This results to reduced insulin levels and increased glucose levels in plasma, leading individuals to easier weight gain and higher BMI.

LEPR (7,8,9) is also involved in regulation of adipose (fat) tissue mass. Its functions in hypothalamus influence the feeling of satiety and energy balance. The type of the gene affects the feeding behavior and the susceptibility of individuals to weight gain and obesity. Mutations in LEPR result to higher circulating levels of leptin. Despite Leptin levels within normal rates are beneficial as they reduce appetite, high levels lead to Leptin resistance and consequently appetite is not properly regulated.

MC4R (10,11) produces a protein that binds to the hormone melanocortin, involved in regulation of appetite and metabolism. Certain mutations have been associated with increased susceptibility to weight gain and obesity.

The group of genes taking part in feeding behavior and the mutations found in such genes creates a panel of genetic variants, like the ones mentioned above, for which nowadays an individual can be tested to know whether his/her genetic profile increase the risk to be obese. It is of outmost importance that for the majority of the genes, the effect of such mutations is modifiable with the appropriate corrective actions. Next step for a person found to have a genetic profile of increased risk, will be to imply the appropriate recommendations in everyday life which can prevent excessive gain weight.

Numerous guidelines by health organizations are available in order to prevent obesity, and worldwide campaigns are trying to motivate people, and especially children, to follow a healthy diet combined with physical exercise. But one could wonder if such strategies have the shown expected results or there is a deeper root for this condition. Undoubtedly following such recommendations for a healthy lifestyle, can cause no harm. But these apply to the general population, taking into account only one aspect of the problem. Nowadays an individual can be provided with a personalized approach, which takes into account not only the person’s lifestyle habits, but also his/her genetic makeup. Nutritional consultation and suggestions on certain supplementation (like appetite suppressants) that will address to an individual’s genetic needs can have far more effective and long-standing results in prevention of obesity and maintenance of normal weight.

Predictive Genomics in service of the Heart health

Written by on September 8th, 2011. Posted in Articles

In recent years the concept of Predictive Genomics has attracted increasingly the interest not only of health professionals but most importantly of the general population. The numerous developments in the field of medical genetics have offered the chance to individuals to have an access to their genetic makeup and understand what kind of information is “hidden” in their genes. A very simple –in procedural way- DNA test can reveal whether a person has increased genetic risk for common conditions compared to the risk of the general population. Identifying genetic changes (mutations) which are involved in certain diseases and thus access a person’s risk based on the genetic profile can provide health professionals with crucial information on prevention and more effective treatments.

The leading causes of death worldwide are diseases which are multi-factorial, for which genetic background as well as environmental factors has a crucial role. Cardiovascular disease is an outstanding example of such conditions.

Cardiovascular disease refers to a defective function of heart and/or vessels. The major cause is atherosclerosis, a condition in which the arteries are thickened, due to accumulation of fatty acids on their walls forming atheromatous plaques. This is very dangerous as progressively the plaque can rupture and block the blood supply to heart or brain and lead to heart attack or stroke respectively. During the past years cardiovascular system problems have increased dramatically –mostly in Western communities- and in some countries have led to death more people than cancer.

Despite the medical community has provided the past years with lifestyle guidelines to prevent cardiovascular risk, these measures apply to the general population, without taking into account the personal genetic profile of individuals. However scientific research has revealed specific DNA alterations that increase importantly the risk for cardiovascular disease, making a person who carries them more susceptible and increasing the need for personalized corrective actions that can modify this higher risk.

A group of such DNA changes are in genes involved in lipids metabolism, like APOA1, APOE, PON1, and CETP (1,2,3,4). Such mutations increase the risk for reduced levels of HDL (good cholesterol) and increased levels of LDL and triglycerides, resulting to higher risk for atheromatosis. Of course we cannot change our genes; however it is of outmost importance that the effect of such mutations can be modified if we apply the appropriate guidelines (like specific dietary habits, exercise and certain clinical screening tests), addressing to our personal genetic background. Limitation of saturated fatty acids and increased intake of ω-3 fatty acids has been proved to be one of the most efficient ways to reduce the cardiovascular risk, even if the genes do not function properly.

Another example is the group of genes involved in homocysteine metabolism, like MTHFR, MTR and CBS (5,6,7,8). DNA changes in such genes are associated with higher homocysteine blood levels, another risk factor for cardiovascular disease.  Again certain personalized guidelines apply to an individual who has a genetic profile indicative of possible defects in homocysteine metabolism. Regular test of folic acid and homocysteine levels, and increase intake of folic acid through diet along with other measures could help individuals overcome such genetic defects.

The list of newly added polymorphisms involved in certain diseases is daily increasing, making the personalized genomic medicine more promising than ever. Nutritional guidelines that address to the specific genetic needs of an individual can undoubtedly be a much more efficient approach in prevention of cardiovascular risk compared to measures for the general population. Nutritional consultation based on an individual’s genetic makeup will be targeted to the roots of the risk and can be implied even from early youth years importantly earlier before atherosclerosis develops. Moreover nutritional supplementation can be proposed to enhance the cardiovascular health, providing the individuals with increased intake of certain vitamins and substances that the person tested needs, instead of overloading the body with excessive compounds.

Endurance performance: from genes to training

Written by on September 8th, 2011. Posted in Articles

Talent is a term frequently used to describe a natural ability for which some people are distinguished, referring to an innate component to perform at higher than the median level of population at a certain work/task. The question whether an elite athlete is born with a natural talent or is “made” through adaptation to training has for many years concerned scientists and professionals involved in sports. Nowadays it is well accepted that there are many factors determining elite athletes; genetic makeup and environment (training, social environment, nutrition) playing both a crucial role. These factors determine also the type of sport where an individual shows a better level of competence, either a sport requiring increased endurance capacity and/or muscle performance.

Focusing on endurance, there are many factors that affect a person’s performance. VO2 max is the most often mentioned when analyzing endurance performance. It refers to maximal oxygen uptake (or aerobic capacity) and is defined as the maximum capacity of the body to transport and use oxygen during exercise. Athletes of endurance sports (e.g. long distance running, swimming, cycling, etc.) performing at high levels of competition have been genetically “gifted”, carrying often specific DNA variants (polymorphisms) in genes involved in metabolism, energy production and muscles formation. Such DNA variations can provide a person with an increased innate ability to have a higher VO2 max, increased exercise economy, and increased aerobic energy production.

Regarding VO2max related genes, VEGF is an example. This gene is involved in angiogenesis. The cells of vascular system, in which blood flows, receive a signal to grow and multiply. This is crucial before and after intensive exercise when blood flow needs to provide the muscle tissues with more oxygen. The type of the gene is associated with the oxygen supplies in muscles and affects the endurance capacity of individuals.

ACE is a well examined gene in relation to endurance capacity, due to its role in cardiovascular system. ACE encodes an enzyme that converts Angiotensin I to Angiotensin II and is involved in the function of cardiovascular system and muscle performance. The levels of the enzyme affect the regulation of blood pressure and are associated with the levels of lipids, glucose and total cholesterol in blood. One of the polymorphisms extensively studied is the I/D, referring to an insertion (I) in the gene. Individuals who carry the variant I, are shown to have increased rate of energy production during incremental exercise, which permits the muscles to perform better in activities with longer duration.

Another polymorphism in gene HIF-1 is associated with a significant advantage of endurance capacity, affecting the oxygen and energy supplies in muscles. This variant results to increased activation of other genes involved in energy metabolism and transport of oxygen to muscles. Athletes seem also to respond very good to high altitude training.

Moreover polymorphisms in genes involved energy production and expenditure energy either from carbohydrates and/or, like PPARD and ADRB2, can affect importantly the genetic tendency of an individual regarding endurance performance levels.

The panel of polymorphisms affecting endurance constantly is constantly enriched with new research data. However for a number of DNA variants the scientific data are quite strong. DNA tests available in the market worldwide offer the chance for individuals to discover their personal genetic advantages or barriers regarding performance in endurance sports. Such tests do not only address to professional athletes but also to amateurs, who just wish to make the right choice of sport or enhance their performance in the sport they are already involved in.

What needs to be emphasized when analyzing the effect of such DNA variants, is that despite the fact that our genetic makeup is something we carry for a lifetime and cannot be altered, it is possible to modify to an important extent the effect of certain polymorphisms. Individualized consultation regarding endurance training strategies based on the genetic profile is now feasible. With the appropriate guidance even people who carry disadvantageous polymorphisms can increase importantly their VO2 max and exercise economy. Adaptation to endurance training will be significantly more effective when sports professionals are aware of the genetic limits of their athlete.

Moreover knowing the genetic needs of an athlete, makes it much easier to choose the appropriate supplementation that will address to the personal needs for certain nutrients.

Undoubtedly sports’ training is moving towards a much more personalized approach of the athlete, taking advantage of the genetic “insight” that science nowadays offers.

DNA & Genes: we look alike but we are not the same

Written by on September 8th, 2011. Posted in Articles

All human characteristics – from the colour of our hair and even our personality to our physical condition and vulnerability to disease – are to a significant degree defined by the genetic information hidden in our DNA! Genes ­ which are particular segments of the DNA – control traits, characteristics and overall health. Although more than 99% of human DNA is identical among all people, it is the remaining 1% that makes us each unique. These tiny differences are called mutations.

Predictive Genomics is the field of medicine that deals with the detection of such mutations which are associated with certain traits, characteristics or common polygenic – multifactorial diseases.

The Predictive Genomics DNA Testing aims to reveal important information on the genetic profile of an individual regarding health risks and general physical condition. Such testing mainly focus on mutations which are relevant to certain biological systems and can – to a significant degree – be modifiable by appliance of Medical, Nutritional and general lifestyle guidelines. These measurers based on an individual’s genetic profile have the major advantage of being personalized and thus have are significantly more efficient compared to guidelines addressing to the general population.

Genetic risks and Nutrition

Over the past few years the scientific research in genetics has revealed several variants in the genome which can increase risks for certain health conditions, increase sensitivity to weight gain and predispose to problems in feeding behavior. These mutations are not proven to be causative, but they rather act accumulatively, increasing the risk for disease. In such cases the role of dietary habits becomes crucial, as they can trigger or prevent the manifestation of certain conditions.

For example a person may be found with an increased risk for cardiovascular disease due to accumulation of mutations in genes regulating lipid levels, like APOA1, APOE, PON1, and CETP (1,2,3,4). The dietary habits should be adjusted properly in order to reduce the risk indicated by the genetic profile. Increase intake of ω-3 fatty acids, found in fish, is proved to be a significant ally in prevention of a heart attack or stroke, as they can modify the expression of genes involved in atherosclerosis. On the other hand the increased consumption of saturated fats, found in red meat and full-fat dairy products, affects negatively the function of the cardiovascular system.

Another example is a woman’s genetic profile that is associated with increased risk for osteoporosis. In this case the studies have shown that increased intake of Calcium and Vitamin D confers importantly in prevention of the disease, or even if osteoporosis develops it could prevent severe symptoms, like frequent and serious bone fractures (5,6,7).

Genetic needs & Nutrition

Apart from reducing the risks for certain conditions, the genetic profile can indicate increased needs of an individual for specific nutrients.

There are specific genes with a crucial role in detoxification and anti-oxidation. These are very important functions for cells in order to deactivate toxic substances, which are either by-products of metabolism or came into the body from the environment. Such substances if not removed can cause serious damages in the DNA with harmful consequences to the health, like development of cancer. In case a genetic profile is indicative of risk for defects in anti-oxidation and detoxifications (with several mutations in genes like GSTT1, GSTM1, CAT), then the individual has increased needs for foods rich in antioxidants, like Vitamins A, C, E, found in fresh fruits and vegetables, nuts, etc. (8,9,10).

Scientific research in human genome has shown already significant evidence regarding the ways that genes interact with nutrition. Therefore it is becoming crucial for Nutritionists and other health professionals to use this knowledge when address to an individual, offering advice that serves certain and personalized needs.