The relationship between peripheral blood mononuclear cells telomere length and diet - unexpected effect of red meat

Telomeres are special structures consisting of repeating DNA chain sequences (TTAGGG) and a complex of few proteins. They are located at the ends of chromosomes and play a role in covering the cell genome and controlling number of cell divisions. Thus, affect cell lifespan. When shortening of telomeres during cell division reaches a critical length, cellular senescence is triggered. Since cellular longevity is affected by telomere length, individuals with longer telomeres should expect higher life expectancy. Very short telomere lengths may activate different repair mechanisms e.g. unlock telomerase – enzyme that can rebuild telomere sequences or ALT (Alternative Lengthening of Telomeres), which can lead to cell immortalization and tumor growth.

Numerous factors can affect shortening and rebuilding of telomeres [1–4], but previous studies did not yield a clear answer to the question what is a relationship between telomere length and some disorders [5, 6] or life expectancy [7, 8].

Diet is a common variable that can have significant impact on human health. Compliance with dietary pyramid is required for maintaining wellbeing. At the top of the pyramid is red meat, which should be eaten with moderation, preferably two or three times a week. Red meat is a good source of high amounts of protein and vitamins, especially B₁, B₁₂, PP and easily assimilable iron. Excessive consumption of red meat is accompanied by an increased ingestion of dietary fat with low level of polyunsaturated fatty acids (PUFA), and toxic substances formed during thermal treatment of meat. It may also affect the serum lipid profile while raising LDL concentration – which is widely recognized as a risk factor for cardiovascular diseases [9]. Several studies have shown that high red meat consumption can increase the incidence of colorectal and breast cancer [10–14], and DNA damage. Greater intake of red meat can induce DNA damage and may have an impact on the “Telomere Length” (TL). Main sources of DNA damage are oxidative stress [15] and inflammation. Heme iron from meat can cause DNA damage in vitro through lipid peroxidation products [16]. Increased intake of saturated fatty acids (SFA) may induce oxidative stress and thus enhance DNA-damage [17, 18].

The aim of this 3-year prospective observational study was to determine the effect of diet, smoking habit, physical activity and education on telomere length of peripheral blood mononuclear cells (PBMC). Results of a cross-sectional analysis of baseline data are presented.

This study established a relationship between the relative length of telomeres in peripheral blood mononuclear cells and the frequency of eating red meat. This finding differs from those published by Lee YJ et al. [21] on the impact of dietary patterns on telomere length. This study showed that diet rich with red meat can decrease leucocyte telomere length 10 years after receiving diet data. Our participants had had blood samples collected just after filling out food frequency questionnaire. Hence we analyzed the relationship without any time shift. Our study population was a little younger (18–65 vs. 40–69 at baseline) and eating habits differ between Poland and Korea. Similarly to Lee YJ et al., a relationship was observed in colonocytes of patients who consume higher amounts of red meat [22] but not in those who ate white meat. As mentioned in the introduction, substances that enter the body along with red meat (lipids, heme iron, N-nitroso compounds) can damage the genetic material. This process is well researched in cells directly related to the digestion of red meat products, in terms particularly of carcinogenesis [23–25] can damage the genetic material. Cooking, frying and especially grilling generates substances with mutagenic activity: heterocyclic amines (HCA), polycyclic aromatic hydrocarbons (PAH), lipid peroxides, wherein the amount is dependent on the temperature of meat processing [26]. Increased consumption of processed meat correlates positively with the likelihood of breast cancer [27, 28] and negatively with leucocyte telomere length [29]. Telomere sequences may also be the site of DNA damage [15]. However, some lipid peroxidation products can reduce the risk of carcinogenesis [30]. Carnosine, a dipeptide found in red meat may have a protective effect on telomeres [31]. There is also a published study indicating the negative influence of diet devoid of meat on health status, especially increased incidence of cancer and mental health disorders [32]. This finding can support the concept of positive effects of red meat on health and is also consistent with the results of our study. The positive relationship between diet rich in red meat and the occurrence of tumors of distant organs from the digestive tract may be due to activity of red meat derivatives in the whole body. Peripheral blood mononuclear cells seem to be a good material for the analysis of the impact of red meat derivatives on the body. They are easy to isolate and count. They circulate all over the body and are exposed to the nutrient. Analysis of genetic material derived from these cells allows detection of factors that can influence changes in the genome of other tissues [33].

Our study on a small group of people managed to demonstrate the relationship between the frequency of consumption of red meat and telomere length. Although no attempt was made to estimate the amount of food products. Some studies indicate the risk of underestimating the amount of food products when using the food frequency questionnaires [34]. Micronutrients (e.g. vitamins) can be related to telomere biology, although there are large discrepancies in publications [35–39]. Our study included healthy subjects without symptoms of vitamin deficiency and who were not taking vitamin supplement. At baseline we did not measure micronutrient levels, assuming that there will not be any differences between physiological values in healthy subjects.

Age-related telomere shortening also occurs in PBMC, but there is a large variation in individual - reduction, stabilization and even increase in length [40] and it is still not fully explained [41]. Intake of food rich in small-to-medium-chain saturated fatty acids (SMSFA: milk, butter, cheese) may be associated with PBMC telomere length – inversely relative [42]. In our study we did not find such a relation (dairy products p = 0.81). Small amounts of SMSFA contained in the meat or used for its preparation (e.g. frying with use of butter) can be one of the TL-modifying factors mentioned above. Although high levels of LDL and HDL concentrations are associated with increased risk of cardiovascular diseases, we did not find any association between these parameters and telomere length. Similar findings were noted in other publications [43].

The study did not confirm negative effect of smoking on telomere length. This finding is probably associated with insufficient sample size. Statistical analysis also excluded the effects of smoking as a covariate modifying the TL among red meat consumers. The observation study continues and we expect changes after its completion.

Physical activity of participants did not correlate with telomere length. Two study participants with the highest physical activity had longer telomere length than others, but this difference could not be included in statistical calculations. This may suggest that only intense physical effort as opposed to mild or moderate may modify the biology of telomeres [44, 45]. Body mass index (BMI) can be associated with telomere length and there are studies in large groups of people defining the rate of TL change per BMI unit [46, 47]. We did not find any anthropometric associations – straight or reverse. Adjusting data with BMI or WHR as continuous factors did not significantly change red meat diet impact on PBMC telomere length.

Many studies indicate the relationship between TL and education level [48–50]. Less educated people are on lower incomes, often consume poor-quality foods (stale or processed) [51] containing harmful substances, which damage the genetic material. Our participants did not differ in TL among education levels, mentioned studies were based on the analysis of large populations where identifying weak dependence is easier and effect of covariates is smaller. Additionally - in contrast to our study - tests were performed among groups of people with similar age.

In conclusion, our study findings are at the baseline of further observations of TL changes in response to food and behavior factors. Although we found a relatively strong relationship, it should be treated as a guide for further research on a larger group of people.

ALT, Alternative Lengthening of Telomeres; ANCOVA, analysis of covariance; ANOVA, analysis of variance; BMI, Body Mass Index; CI, coefficient interval; EDTA, ethylenediaminetetraacetic acid; FFQ, food frequency questionnaire; HCA, heterocyclic amines; HDL, high-density lipoprotein; HSD, honest significant difference; LDL, low-density lipoprotein; PAH, polycyclic aromatic hydrocarbons; PBMC, peripheral blood mononuclear cells; PUFA, polyunsaturated fatty acids; rtPCR, quantitive real-time polymerase chain reaction; SD, standard deviation; SFA, saturated fatty acids; SMSFA, small-to-medium-chain saturated fatty acids; T/S, telomere to single (copy gene); TL, telomere length; WHR, Waist-Hip Ratio