The enzyme telomerase, through its influence on telomere length, is associated with health and mortality. Four pioneering randomized control trials, including a total of 190 participants, provided information on the effect of mindfulness meditation on telomerase. A meta-analytic effect size of d=0.46 indicated that mindfulness meditation leads to increased telomerase activity in peripheral blood mononuclear cells. These results suggest the need for further large-scale trials investigating optimal implementation of mindfulness meditation to facilitate telomerase functioning.

It is well established that the telomeres at the ends of chromosomes are composed of long arrays of (TTAGGG)n x (CCCTAA)n that form a nucleoprotein complex required for the replication and protection of chromosome ends. Throughout the cell cycle, telomeres also contain a protein component related to the proto-oncogene Myb that is known as TRF1 (telomere TTAGGG repeat binding factor 1) that binds to the duplex array of TTAGGG repeats in the telomere. Previous studies have shown that TRF1 appears to play a role in controlling the length of telomeres by acting as an inhibitor of telomerase. The amount of each of the TRF1(C-19)&TRF1(N-19) was identical to the amount of telomere of the same organ of the same apparently normal individual. Using synthesized basic unit of TTAGGG, as well as CCCTAA, as separate reference control substances for the Bi-Digital O-Ring Test of Resonance Phenomenon between 2 identical substances, we were able to non-invasively measure the approximate amount of TTAGGG and CCCTAA units, in both normal and cancerous human cells. We examined about 30 apparently normal subjects (both Asian and Caucasian in both sex). The subjects' ages ranged from infancy to 76 years. Each subject was first examined using TTAGGG as a control substance and then examined using CCCTAA as a control substance. The amount of telomere in various cancer tissues are almost always higher than that of normal tissue of the same organ. The measured amounts of both TTAGGG and CCCTAA were found to be in an average of 1500-1600 ng for human fetus or infancy and decreased with the advance of age in both sex with the exception of the heart, brain, eyes (retina), testes, and ovaries, which usually remain at the level of the infant, or reduced very little. Individuals in the same age group had a similar range of amounts of both TTAGGG and CCCTAA in the same organ of the same individual, (except for those with unusually low telomeres often had chronic degenerative diseases, and those who had exceptionally high telomere levels often had excellent physical conditions or mental acumen). The amounts of measured TTAGGG and CCCTAA molecules before and after acupuncture on St. 36 in adenocarcinomas and small cell carcinoma coexisting in the lung of a 54-yr.-old Asian male were: telomere in adenocarcinoma decreased from 950 ng to 750 ng and telomere in small cell carcinoma decreased from 770 ng to 600 ng. When the cancer treatment is effective, the amount of telomere is reduced towards the value of the normal internal organ. We found that acupuncture on St.36 on apparently normal subjects increased the telomere levels up to a maximum of more than 2 times their telomere levels prior to the treatment, depending on the method of treatment, but frequently increases were between 60% to 100%. Strong Shiatsu performed on St. 36 produced a somewhat lesser effect than acupuncture. We also determined the amounts of TTAGGG and CCCTAA molecules non-invasively in 3 mummified Egyptian sisters from the 8th Century BC on exhibit at the Museo Egizio in Turin, Italy in order to estimate their approximate ages (at the time of death). The amounts of body telomere were 500 ng, 550 ng, and 750 ng. For the prehistoric Iceman (about 3350 B.C. to 3310 B.C) discovered in 1991 in the Italian Otzal Alps at about 3,200 meters altitude, estimated body telomere was about 400 ng and telomere in brain and heart was 1600 ng, similar to that of a contemporary human being. Although these studies are preliminary, the findings may have potential applications not only in anti-aging, cancer treatments, and pathophysiology of brain and heart, but also for the estimation of the difference in the ages of cadavers studied in archeology and forensic medicine.

It is well established that the telomeres at the ends of chromosomes are composed of long arrays of (TTAGGG)n x (CCCTAA)n that form a nucleoprotein complex required for the replication and protection of chromosome ends. Throughout the cell cycle, telomeres also contain a protein component related to the proto-oncogene Myb that is known as TRF1 (telomere TTAGGG repeat binding factor 1) that binds to the duplex array of TTAGGG repeats in the telomere. Previous studies have shown that TRF1 appears to play a role in controlling the length of telomeres by acting as an inhibitor of telomerase. The amount of each of the TRF1(C-19)&TRF1(N-19) was identical to the amount of telomere of the same organ of the same apparently normal individual. Using synthesized basic unit of TTAGGG, as well as CCCTAA, as separate reference control substances for the Bi-Digital O-Ring Test of Resonance Phenomenon between 2 identical substances, we were able to non-invasively measure the approximate amount of TTAGGG and CCCTAA units, in both normal and cancerous human cells. We examined about 30 apparently normal subjects (both Asian and Caucasian in both sex). The subjects' ages ranged from infancy to 76 years. Each subject was first examined using TTAGGG as a control substance and then examined using CCCTAA as a control substance. The amount of telomere in various cancer tissues are almost always higher than that of normal tissue of the same organ. The measured amounts of both TTAGGG and CCCTAA were found to be in an average of 1500-1600 ng for human fetus or infancy and decreased with the advance of age in both sex with the exception of the heart, brain, eyes (retina), testes, and ovaries, which usually remain at the level of the infant, or reduced very little. Individuals in the same age group had a similar range of amounts of both TTAGGG and CCCTAA in the same organ of the same individual, (except for those with unusually low telomeres often had chronic degenerative diseases, and those who had exceptionally high telomere levels often had excellent physical conditions or mental acumen). The amounts of measured TTAGGG and CCCTAA molecules before and after acupuncture on St. 36 in adenocarcinomas and small cell carcinoma coexisting in the lung of a 54-yr.-old Asian male were: telomere in adenocarcinoma decreased from 950 ng to 750 ng and telomere in small cell carcinoma decreased from 770 ng to 600 ng. When the cancer treatment is effective, the amount of telomere is reduced towards the value of the normal internal organ. We found that acupuncture on St.36 on apparently normal subjects increased the telomere levels up to a maximum of more than 2 times their telomere levels prior to the treatment, depending on the method of treatment, but frequently increases were between 60% to 100%. Strong Shiatsu performed on St. 36 produced a somewhat lesser effect than acupuncture. We also determined the amounts of TTAGGG and CCCTAA molecules non-invasively in 3 mummified Egyptian sisters from the 8th Century BC on exhibit at the Museo Egizio in Turin, Italy in order to estimate their approximate ages (at the time of death). The amounts of body telomere were 500 ng, 550 ng, and 750 ng. For the prehistoric Iceman (about 3350 B.C. to 3310 B.C) discovered in 1991 in the Italian Otzal Alps at about 3,200 meters altitude, estimated body telomere was about 400 ng and telomere in brain and heart was 1600 ng, similar to that of a contemporary human being. Although these studies are preliminary, the findings may have potential applications not only in anti-aging, cancer treatments, and pathophysiology of brain and heart, but also for the estimation of the difference in the ages of cadavers studied in archeology and forensic medicine.

BACKGROUND:Telomeres are protective DNA-protein complexes at the end of linear chromosomes that promote chromosomal stability. Telomere shortness in human beings is emerging as a prognostic marker of disease risk, progression, and premature mortality in many types of cancer, including breast, prostate, colorectal, bladder, head and neck, lung, and renal cell. Telomere shortening is counteracted by the cellular enzyme telomerase. Lifestyle factors known to promote cancer and cardiovascular disease might also adversely affect telomerase function. However, previous studies have not addressed whether improvements in nutrition and lifestyle are associated with increases in telomerase activity. We aimed to assess whether 3 months of intensive lifestyle changes increased telomerase activity in peripheral blood mononuclear cells (PBMC).

METHODS:30 men with biopsy-diagnosed low-risk prostate cancer were asked to make comprehensive lifestyle changes. The primary endpoint was telomerase enzymatic activity per viable cell, measured at baseline and after 3 months. 24 patients had sufficient PBMCs needed for longitudinal analysis. This study is registered on the ClinicalTrials.gov website, number NCT00739791.

FINDINGS:PBMC telomerase activity expressed as natural logarithms increased from 2.00 (SD 0.44) to 2.22 (SD 0.49; p=0.031). Raw values of telomerase increased from 8.05 (SD 3.50) standard arbitrary units to 10.38 (SD 6.01) standard arbitrary units. The increases in telomerase activity were significantly associated with decreases in low-density lipoprotein (LDL) cholesterol (r=-0.36, p=0.041) and decreases in psychological distress (r=-0.35, p=0.047).

INTERPRETATION:Comprehensive lifestyle changes significantly increase telomerase activity and consequently telomere maintenance capacity in human immune-system cells. Given this finding and the pilot nature of this study, we report these increases in telomerase activity as a significant association rather than inferring causation. Larger randomised controlled trials are warranted to confirm the findings of this study.

Mindfulness-based stress reduction (MBSR) reduces symptoms of depression, anxiety, and fear of recurrence among breast cancer (BC) survivors. However, the effects of MBSR (BC) on telomere length (TL) and telomerase activity (TA), known markers of cellular aging, psychological stress, and disease risk, are not known. This randomized, wait-listed, controlled study, nested within a larger trial, investigated the effects of MBSR (BC) on TL and TA. BC patients (142) with Stages 0-III cancer who had completed adjuvant treatment with radiation and/or chemotherapy at least 2 weeks prior to enrollment and within 2 years of completion of treatment with lumpectomy and/or mastectomy were randomly assigned to either a 6-week MBSR for BC program or a usual care. Assessments of TA and TL were obtained along with psychological measurements at baseline, 6 weeks, and 12 weeks after completing the MBSR(BC) program. The mean age of 142 participants was 55.3 years; 72% were non-Hispanic White; 78% had Stage I or II cancer; and 36% received both chemotherapy and radiation. In analyses adjusted for baseline TA and psychological status, TA increased steadily over 12 weeks in the MBSR(BC) group (approximately 17%) compared to essentially no increase in the control group (approximately 3%, p<.01). In contrast, no between-group difference was observed for TL (p = .92). These results provide preliminary evidence that MBSR(BC) increases TA in peripheral blood mononuclear cells from BC patients and have implications for understanding how MBSR(BC) may extend cell longevity at the cellular level.

BACKGROUND: Telomerase activity is a predictor of long-term cellular viability, which decreases with chronic psychological distress (Epel et al., 2004). Buddhist traditions claim that meditation decreases psychological distress and promotes well-being (e.g., Dalai Lama and Cutler, 2009). Therefore, we investigated the effects of a 3-month meditation retreat on telomerase activity and two major contributors to the experience of stress: Perceived Control (associated with decreased stress) and Neuroticism (associated with increased subjective distress). We used mediation models to test whether changes in Perceived Control and Neuroticism explained meditation retreat effects on telomerase activity. In addition, we investigated whether two qualities developed by meditative practice, increased Mindfulness and Purpose in Life, accounted for retreat-related changes in the two stress-related variables and in telomerase activity. METHODS: Retreat participants (n=30) meditated for∼6h daily for 3 months and were compared with a wait-list control group (n=30) matched for age, sex, body mass index, and prior meditation experience. Retreat participants received instruction in concentrative meditation techniques and complementary practices used to cultivate benevolent states ofmind (Wallace, 2006). Psychological measures were assessed pre- and post-retreat. Peripheral blood mononuclear cell samples were collected post-retreat for telomerase activity. Because there were clear, a priori hypotheses, 1-tailed significance criteria were used throughout. RESULTS: Telomerase activity was significantly greater in retreat participants than in controls at the end of the retreat (p<0.05). Increases in Perceived Control, decreases in Neuroticism, and increases in both Mindfulness and Purpose in Life were greater in the retreat group (p<0.01). Mediation analyses indicated that the effect of the retreat on telomerase was mediated by increased Perceived Control and decreased Neuroticism. In turn, changes in Perceived Control and Neuroticism were both partially mediated by increased Mindfulness and Purpose in Life. Additionally, increases in Purpose in Life directly mediated the telomerase group difference, whereas increases in Mindfulness did not. CONCLUSIONS: This is the first study to link meditation and positive psychological change with telomerase activity. Although we did not measure baseline telomerase activity, the data suggest that increases in perceived control and decreases in negative affectivity contributed to an increase in telomerase activity, with implications for telomere length and immune cell longevity. Further, Purpose in Life is influenced by meditative practice and directly affects both perceived control and negative emotionality, affecting telomerase activity directly as well as indirectly.

Relatively short telomere length may serve as a marker of accelerated aging, and shorter telomeres have been linked to chronic stress. Specific lifestyle behaviors that can mitigate the effects of stress might be associated with longer telomere lengths. Previous research suggests a link between behaviors that focus on the well-being of others, such as volunteering and caregiving, and overall health and longevity. We examined relative telomere length in a group of individuals experienced in Loving-Kindness Meditation (LKM), a practice derived from the Buddhist tradition which utilizes a focus on unselfish kindness and warmth towards all people, and control participants who had done no meditation. Blood was collected by venipuncture, and Genomic DNA was extracted from peripheral blood leukocytes. Quantitative real time PCR was used to measure relative telomere length (RTL) (Cawthon, 2002) in fifteen LKM practitioners and 22 control participants. There were no significant differences in age, gender, race, education, or exposure to trauma, but the control group had a higher mean body mass index (BMI) and lower rates of past depression. The LKM practitioners had longer RTL than controls at the trend level (p=.083); among women, the LKM practitioners had significantly longer RTL than controls, (p=.007), which remained significant even after controlling for BMI and past depression. Although limited by small sample size, these results offer the intriguing possibility that LKM practice, especially in women, might alter RTL, a biomarker associated with longevity.

Relatively short telomere length may serve as a marker of accelerated aging, and shorter telomeres have been linked to chronic stress. Specific lifestyle behaviors that can mitigate the effects of stress might be associated with longer telomere lengths. Previous research suggests a link between behaviors that focus on the well-being of others, such as volunteering and caregiving, and overall health and longevity. We examined relative telomere length in a group of individuals experienced in Loving-Kindness Meditation (LKM), a practice derived from the Buddhist tradition which utilizes a focus on unselfish kindness and warmth towards all people, and control participants who had done no meditation. Blood was collected by venipuncture, and Genomic DNA was extracted from peripheral blood leukocytes. Quantitative real time PCR was used to measure relative telomere length (RTL) (Cawthon, 2002) in fifteen LKM practitioners and 22 control participants. There were no significant differences in age, gender, race, education, or exposure to trauma, but the control group had a higher mean body mass index (BMI) and lower rates of past depression. The LKM practitioners had longer RTL than controls at the trend level (p=.083); among women, the LKM practitioners had significantly longer RTL than controls, (p=.007), which remained significant even after controlling for BMI and past depression. Although limited by small sample size, these results offer the intriguing possibility that LKM practice, especially in women, might alter RTL, a biomarker associated with longevity.

BACKGROUND:Telomere length may be a marker of biological aging. Multivitamin supplements represent a major source of micronutrients, which may affect telomere length by modulating oxidative stress and chronic inflammation.

OBJECTIVE:The objective was to examine whether multivitamin use is associated with longer telomeres in women.

DESIGN:We performed a cross-sectional analysis of data from 586 early participants (age 35-74 y) in the Sister Study. Multivitamin use and nutrient intakes were assessed with a 146-item food-frequency questionnaire, and relative telomere length of leukocyte DNA was measured by quantitative polymerase chain reaction.

RESULTS:After age and other potential confounders were adjusted for, multivitamin use was associated with longer telomeres. Compared with nonusers, the relative telomere length of leukocyte DNA was on average 5.1% longer among daily multivitamin users (P for trend = 0.002). In the analysis of micronutrients, higher intakes of vitamins C and E from foods were each associated with longer telomeres, even after adjustment for multivitamin use. Furthermore, intakes of both nutrients were associated with telomere length among women who did not take multivitamins.

CONCLUSION:This study provides the first epidemiologic evidence that multivitamin use is associated with longer telomere length among women.

Epidemiological studies indicate that among other early life challenges, maternal infection with influenza during pregnancy increased the risk of developing schizophrenia in the child. One morphological manifestation of schizophrenia is hippocampal atrophy. In the hippocampus, playing a key role in learning and memory formation, new granule cell neurons are produced throughout life from resident precursor cells. We hypothesize that individuals exposed to a maternal anti-viral immune response would presumably enter life with a challenged neural precursor cell pool and might later be susceptible to psychiatric pathologies due to reduced adult neurogenesis. We used the injection of double-stranded RNA (polyriboinosinicpolyribocytidylic acid - PolyI:C) in pregnant C57Bl/6 and nestin-GFP reporter mice to induce a maternal viral-like infection and schizophrenia-like behavior in the offspring. In the progeny we found impairments in the open field test and in sensorimotor gating as measured by pre-pulse inhibition of the startle response. The behaviorial deficits were accompanied by reduced baseline adult hippocampal neurogenesis. Telomerase activity in neural precursor cells was reduced from birth on and telomere shortening was found in the same cell type in adult life. When we subjected the progeny of viral-like infected dams to voluntary exercise, a known stimulus of adult hippocampal neurogenesis, we could rescue the phenotype in behavior, adult neurogenesis, and cellular senescence. In summary, maternal viral-like immune response reduced telomerase activity and resulted in telomere shortening in neural precursor cells. Further we demonstrate that beneficial behavioral and cellular effects induced by exercise can be studied in a rodent model of schizophrenia.

OBJECTIVE:To summarise and discuss the association between telomerase activity and psychological stress, mental disorders and lifestyle factors.

METHOD:A systematic review was carried out to identify prospective or retrospective studies and interventions published up to June 2015 that reported associations between telomerase activity and psychological stress, mental disorders and lifestyle factors. Electronic data bases of PubMed, ProQuest, CINAHL and Google Scholar were searched.

RESULTS:Twenty six studies on humans measured telomerase activity in peripheral blood mononuclear cells (PBMCs) or leukocytes and examined its association with psychological stress, mental disorders and lifestyle factors. Of those studies, three reported significantly decreased telomerase activity in individuals under chronic psychological stress. Interestingly, one of the three studies found that acute laboratory psychological stress significantly increased telomerase activity. Nine studies reported mixed results on association between mental disorders and telomerase activity. Of the nine studies, five reported that major depressive disorder (MDD) was associated with significantly increased telomerase activity. In thirteen out of fourteen studies on lifestyle factors, it was reported that physical exercise, diet micronutrient supplementation, mindfulness meditation, Qigong practice or yoga mediation resulted in increase in telomerase activity. In addition, two studies on animal models showed that depression-like behaviour was associated with decreased hippocampus telomerase activity. Five animal studies showed that physical exercise increased telomerase activity by cell-type-specific and genotype-specific manners.

CONCLUSION:Although multi-facet results were reported on the association between telomerase activity and psychological stress, mental disorders and lifestyle factors, there were some consistent findings in humans such as (1) decreased telomerase activity in individuals under chronic stress, (2) increased telomerase activity in individuals with MDD, and (3) increased telomerase activity in individuals under lifestyle interventions. Animal studies showed that physical exercise increased telomerase activity in specific cell-types. However, the exact mechanisms for the changes in telomerase activity have not been elucidated. We propose conglomerate models connecting chronic psychological stress, depression, mediation and physical exercise to telomerase activation. Several areas for future research are suggested.

BACKGROUND:Telomeres are potential markers of mitotic cellular age and are associated with physical ageing process. Long-term endurance training and higher aerobic exercise capacity (VO(2max)) are associated with improved survival, and dynamic effects of exercise are evident with ageing. However, the association of telomere length with exercise training and VO(2max) has so far been inconsistent. Our aim was to assess whether muscle telomere length is associated with endurance exercise training and VO(2max) in younger and older people.

METHODS:Twenty men; 10 young (22-27 years) and 10 old (66-77 years), were studied in this cross-sectional study. Five out of 10 young adults and 5 out of 10 older were endurance athletes, while other halves were exercising at a medium level of activity. Mean telomere length was measured as telomere/single copy gene-ratio (T/S-ratio) using quantitative real time polymerase chain reaction. VO(2max) was measured directly running on a treadmill.

RESULTS:Older endurance trained athletes had longer telomere length compared with older people with medium activity levels (T/S ratio 1.12±0.1 vs. 0.92±0.2, p = 0.04). Telomere length of young endurance trained athletes was not different than young non-athletes (1.47±0.2 vs. 1.33±0.1, p = 0.12). Overall, there was a positive association between T/S ratio and VO(2max) (r = 0.70, p = 0.001). Among endurance trained athletes, we found a strong correlation between VO(2max) and T/S ratio (r = 0.78, p = 0.02). However, corresponding association among non-athlete participants was relatively weak (r = 0.58, p = 0.09).

CONCLUSION:Our data suggest that VO(2max) is positively associated with telomere length, and we found that long-term endurance exercise training may provide a protective effect on muscle telomere length in older people.

Cell sheet engineering has been developed as an alternative approach to improve mesenchymal stem cell-mediated tissue regeneration. In this study, we found that vitamin C (Vc) was capable of inducing telomerase activity in periodontal ligament stem cells (PDLSCs), leading to the up-regulated expression of extracellular matrix type I collagen, fibronectin, and integrinβ1, stem cell markers Oct4, Sox2, and Nanog as well as osteogenic markers RUNX2, ALP, OCN. Under Vc treatment, PDLSCs can form cell sheet structures because of increased cell matrix production. Interestingly, PDLSC sheets demonstrated a significant improvement in tissue regeneration compared with untreated control dissociated PDLSCs and offered an effective treatment for periodontal defects in a swine model. In addition, bone marrow mesenchymal stem cell sheets and umbilical cord mesenchymal stem cell sheets were also well constructed using this method. The development of Vc-mediated mesenchymal stem cell sheets may provide an easy and practical approach for cell-based tissue regeneration.