Telomeres and lifestyle factors: Roles in cellular aging

doi:10.1016/j.mrfmmm.2011.08.003

Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis

Volume 730, Issues 1–2, 1 February 2012, Pages 85-89

https://doi.org/10.1016/j.mrfmmm.2011.08.003 Get rights and content

Abstract

Recent research has demonstrated that telomere maintenance might be a key integrating point for the cumulative effects of genetic, environmental and lifestyle factors on aging and aging-related diseases. It is timely to ‘take stock’ of where this work has led the field. This review summarizes studies that have examined associations between lifestyle factors and telomere length and telomerase activity. In most of the studies described in this chapter, telomere length was measured in leukocytes (LTL) or peripheral blood mononuclear cells (PBMCs), taken from blood draws from the study subjects. Much of this chapter focuses on psychological stress, a widespread factor often intimately tied in with lifestyle or behavioral factors that in turn are related to risks of clinical diseases. Together, these findings suggest that cellular aging is linked to a range of influences, with an individual's life events and lifestyle parameters playing significant roles. Lastly, we propose possible biochemical mechanisms that mediate these associations and discuss future directions.

Highlights

► Leukocyte telomere length and telomerase activity are linked to a wide variety of aging-related diseases and their risks. ► Telomere maintenance may integrate the effects of genetic, environmental and life style factors on aging-related diseases. ► Psychological stress, as an important life style and behavioral factor, is associated with shorter telomere length. ► Stress hormones, inflammation and oxidative stress are proposed mechanisms that mediate the above-mentioned associations.

Section snippets

Perceived stress and adverse life events

Severe or chronic psychological stress is known to accelerate biological aging, as defined in broad sense, although the mechanisms by which this occurs have been elusive. A 2004 study by Epel et al. first reported a novel correlation between short telomere length, low telomerase activity and perceived chronic psychological stress in mothers, some who had a healthy child and some who were caregivers of chronically sick children [1]. Those who scored high on a 10-item questionnaire assessing

Stress and stress-related psychiatric conditions

Depression and post-traumatic stress disorder (PTSD) are closely linked to, and attributable to, exposure to chronic or severe psychological stress (reviewed by [19]. Several reports have found shorter telomere length in patients with mood disorders including major depressive disorder, and bipolar depressive disorder with and without anxiety [20], [21], [22]. In a small study, Wolkowitz et al. found only marginally shorter telomeres in individuals with major clinical depression compared with

Telomere length and temperament

Damjanovic et al., when examining LTL in older caregivers, found that simply being a caregiver was related to shorter LTL and our recent study on dementia caregivers replicates this finding (O’Donovan et al., under review). However, many studies of stressor exposure find that it is individual differences, such as perception of stress, or personality, that are linked to stress-related physiology. For example, Epel et al.’s 2004 study first demonstrated that level of perceived stress, as opposed

Dietary biomarkers and nutritional intake

Unhealthy life style factors including smoking [25], [26], [27], [28], [29], [30], consumption of processed meat [31] and high BMI [32], [33], [34], [35], [36], [37] have been reported to correlate with short telomere length. Several studies have now reported relationships between dietary biomarkers and telomere length. Higher plasma vitamin D level was associated with longer telomere length in women [38]. Another study reported high plasma homocysteine was associated with shorter telomere

Interventions

Cross-sectional correlations between healthy life style factors and telomere length and telomerase activity have been reported in various studies, and provide the compelling possibility that LTL is malleable and partly under our control. For example, in a sample of 318 subjects, 40–64 years old, with no previous diagnosis of coronary heart disease, stroke, diabetes or cancer, shorter LTL was related to presence of coronary artery calcium (CAC) [43]. However, greater fruit and vegetable

Possible mechanisms mediating relationships between life style factors and telomere length

What potential mechanisms and pathways mediate the relationship between life style factors and telomere length? Research has focused on several inter-related biochemical pathways: stress hormones, inflammation and oxidative stress. Treatment of stimulated T-cells with the stress hormone cortisol in vitro causes decreases in cell proliferation, decreased telomerase activity and lower hTERT mRNA levels after cell activation [48]. In vivo, elevated levels of epinephrine, norepinephrine and

Is telomerase activation a compensatory mechanism induced by telomere shortness?

The Epel et al. 2004 study showed that low basal telomerase activity in unstimulated PBMCs is associated with worse stress in women without frank disease. This correlation was confirmed in a more recent study with women caregivers of dementia patients by the same author [65] as well as in other studies that showed increases in telomerase activity over a 3 month period were associated with improved health profiles [46], [47]. However, other studies have found the opposite relationship. In a

Future directions

While cross-sectional studies are abundant, there have been very few longitudinal studies of telomere length [72], [73], [74], [75], [76], [77]. One consistent finding from the published longitudinal data is that the rate of telomere length change over time is inversely related to the baseline telomere length [72], [76], [77]. The mechanisms that regulate this phenomenon are of great interest. The available studies have shown that telomere length trajectory over time predicts health outcome.

Conflict of interest

Drs. Jue Lin, Elissa Epel and Elizabeth Blackburn are co-founders of Telome Health Inc., a diagnostic company measuring telomere biology.

References (83)

A.R Tyrka et al.
Childhood maltreatment and telomere shortening: preliminary support for an effect of early stress on cellular aging
Biol. Psychiatry
(2010)
N.M Simon et al.
Telomere shortening and mood disorders: preliminary support for a chronic stress model of accelerated aging
Biol. Psychiatry
(2006)
A. O’Donovan et al.
Pessimism correlates with leukocyte telomere shortness and elevated interleukin-6 in post-menopausal women
Brain Behav. Immun.
(2009)
A.M. Valdes et al.
Obesity, cigarette smoking, and telomere length in women
Lancet
(2005)
J.A. Nettleton et al.
Associations between microalbuminuria and animal foods, plant foods, and dietary patterns in the Multiethnic Study of Atherosclerosis
Am. J. Clin. Nutr.
(2008)
R.Y. Zee et al.
Mean leukocyte telomere length shortening and type 2 diabetes mellitus: a case-control study
Transl. Res.
(2010)
J.B Richards et al.
Higher serum vitamin D concentrations are associated with longer leukocyte telomere length in women
Am. J. Clin. Nutr.
(2007)
J.B. Richards et al.
Homocysteine levels and leukocyte telomere length
Atherosclerosis
(2008)
L. Paul et al.
Telomere length in peripheral blood mononuclear cells is associated with folate status in men
J. Nutr.
(2009)
V.A. Diaz et al.
Effect of healthy lifestyle behaviors on the association between leukocyte telomere length and coronary artery calcium
Am. J. Cardiol.
(2010)

D. Ornish et al.

Increased telomerase activity and comprehensive lifestyle changes: a pilot study

Lancet Oncol.

(2008)

T.L. Jacobs et al.

Intensive meditation training, immune cell telomerase activity, and psychological mediators

Psychoneuroendocrinology

(2011)

J. Choi et al.

Reduced telomerase activity in human T lymphocytes exposed to cortisol

Brain Behav. Immun.

(2008)

E.S. Epel et al.

Cell aging in relation to stress arousal and cardiovascular disease risk factors

Psychoneuroendocrinology

(2006)

M. Irie et al.

Depressive state relates to female oxidative DNA damage via neutrophil activation

Biochem. Biophys. Res. Commun.

(2003)

H. Tsuboi et al.

Depressive symptoms are independently correlated with lipid peroxidation in a female population: comparison with vitamins and carotenoids

J. Psychosom. Res.

(2004)

T. von Zglinicki

Oxidative stress shortens telomeres

Trends Biochem. Sci.

(2002)

C.A Jolly et al.

Life span is prolonged in food-restricted autoimmune-prone (NZB × NZW)F(1) mice fed a diet enriched with (n-3) fatty acids

J. Nutr.

(2001)

J.E Graham et al.

Stress, age, and immune function: toward a lifespan approach

J. Behav. Med.

(2006)

J.P Liu et al.

Regulation of telomerase activity by apparently opposing elements

Ageing Res. Rev.

(2010)

E.S Epel et al.

Dynamics of telomerase activity in response to acute psychological stress

Brain Behav. Immun.

(2010)

M.T Teixeira et al.

Telomere length homeostasis is achieved via a switch between telomerase-extendible and -nonextendible states

Cell

(2004)

B. Britt-Compton et al.

Short telomeres are preferentially elongated by telomerase in human cells

FEBS Lett.

(2009)

M. Vasa-Nicotera et al.

Mapping of a major locus that determines telomere length in humans

Am. J. Hum. Genet.

(2005)

T. Andrew et al.

Mapping genetic loci that determine leukocyte telomere length in a large sample of unselected female sibling pairs

Am. J. Hum. Genet.

(2006)

E.S. Epel et al.

Accelerated telomere shortening in response to life stress

Proc. Natl. Acad. Sci. U.S.A.

(2004)

A.K Damjanovic et al.

Accelerated telomere erosion is associated with a declining immune function of caregivers of Alzheimer's disease patients

J. Immunol.

(2007)

L.F. Cherkas et al.

The effects of social status on biological aging as measured by white-blood-cell telomere length

Aging Cell

(2006)

A. Steptoe et al.

Educational attainment but not measures of current socioeconomic circumstances are associated with leukocyte telomere length in healthy older men and women

Brain Behav. Immun.

(2011)

J. Adams et al.

No association between socio-economic status and white blood cell telomere length

Aging Cell

(2007)

G.D Batty et al.

Socioeconomic status and telomere length: the West of Scotland Coronary Prevention Study

J. Epidemiol. Community Health

(2009)

R.A. Risques et al.

Leukocyte telomere length is associated with disability in older U.S. Population

J. Am. Geriatr. Soc.

(2010)

J. Woo et al.

Older men with higher self-rated socioeconomic status have shorter telomeres

Age Ageing

(2009)

A. Aviv

Telomeres, sex, reactive oxygen species, and human cardiovascular aging

J. Mol. Med.

(2002)

A. Aviv et al.

The longevity gender gap: are telomeres the explanation?

Sci. Aging Knowl. Environ.

(2005)

S.C. Hunt et al.

Leukocyte telomeres are longer in african americans than in whites: the national heart, lung, and blood institute family heart study and the Bogalusa Heart Study

Aging Cell

(2008)

J. Humphreys et al.

Telomere shortening in formerly abused and never abused women

Biol. Res. Nurs.

(2011)

L. Kananen et al.

Childhood adversities are associated with shorter telomere length at adult age both in individuals with an anxiety disorder and controls

PLoS One

(2010)

J.K Kiecolt-Glaser et al.

Childhood adversity heightens the impact of later-life caregiving stress on telomere length and inflammation

Psychosom. Med.

(2011)

A. O’Donovan et al.

Childhood Trauma Associated with Short Leukocyte Telomere Length in Posttraumatic Stress Disorder

Biol. Psychiatry

(2011)

P.G. Surtees et al.

Life Stress, Emotional Health, and Mean Telomere Length in the European Prospective Investigation into Cancer (EPIC)-Norfolk Population Study

J. Gerontol. A. Biol. Sci. Med. Sci.

(2011)

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Erratum: Does Late-Life Depression Accelerate Aging? (The American Journal of Geriatric Psychiatry (2023) 31(1) (10–13), (S1064748122005139), (10.1016/j.jagp.2022.09.003))
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The fetal programming of telomere biology hypothesis
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Adverse prenatal environmental conditions, including stress, infections, and obesity, are known to be developmental risk factors for certain diseases in later life. This chapter discusses numerous studies from our group that elucidate the effects of prenatal maternal stress on the offspring's susceptibility to disease, the biological mechanisms that drive these effects, and possible ways to prevent or reverse them. In these studies, maternal stress was found to alter several physiological functions—including immune, endocrine, cognitive, and metabolic functions—of the offspring in a manner that predisposes them to a range of diseases in later life. Prenatal maternal stress and higher immune activation resulted in significantly shorter telomeres in offspring tissues, suggesting that the effects of maternal stress on the offspring's susceptibility to disease may in part be mediated by alterations in telomere biology. We submit that telomere biology represents a process of particular interest in the context of fetal programming of health and disease risk. First, this system represents an antecedent cellular phenotype for common age-related disorders. Second, its initial (newborn) setting appears to be particularly important for its long-term effects; and third, its initial setting appears to be plastic and under developmental regulation. We propose that the effects of suboptimal intrauterine conditions on the initial setting of telomere length and telomerase expression/activity capacity may be mediated by the programming actions of stress-related maternal-placental-fetal stress-related pathways in a manner that may ultimately accelerate cellular dysfunction, aging, and disease susceptibility over the lifespan. Overall, the studies discussed in this chapter highlight the importance of maternal mental wellbeing during pregnancy to prevent adverse outcomes in the mother, the offspring, and perhaps future generations too.
Does Late-Life Depression Accelerate Aging?
2023, American Journal of Geriatric Psychiatry
Accelerated telomere erosion in schizophrenia: A literature review
2021, Encephale
La schizophrénie est associée à une espérance de vie diminuée de plus de dix ans. Dans la population générale, l’espérance de vie est fortement corrélée à la longueur des télomères. Une érosion prématurée des télomères pourrait donc rendre compte de cette espérance de vie diminuée dans la schizophrénie. Nous avons réalisé une revue de la littérature portant sur la longueur des télomères dans la schizophrénie, détaillée les différents mécanismes physiopathologiques pouvant sous-tendre une telle association, et enfin dégagé des perspectives thérapeutiques. La littérature montre une diminution de la longueur des télomères chez les sujets souffrant de schizophrénie, mais pas chez les premiers épisodes psychotiques. Ceci suggère que le raccourcissement prématuré des télomères se produit au cours de l’évolution de la maladie via l’activation de phénomènes inflammatoires et oxydatifs qui pourraient être une conséquence physiopathologique de la schizophrénie ou plus vraisemblablement être dus à une exposition répétée des individus à des facteurs de stress. L’érosion prématurée de la longueur des télomères dans la schizophrénie ouvre des perspectives thérapeutiques comme l’utilisation de molécules ayant des actions anti-inflammatoires. Un exercice physique régulier, une alimentation saine, un sommeil de qualité et une meilleure gestion du stress seraient capables de diminuer l’érosion des télomères. Les thérapies de « pleine conscience » semblent également prometteuses dans ce cadre. Enfin, une meilleure compréhension des liens entre stress, inflammation et télomères pourrait avoir un grand intérêt pour mieux comprendre la physiopathologie de la schizophrénie, la morbi-mortalité élevée, améliorer le diagnostic précoce et potentiellement ouvrir des pistes en matière de prévention et de traitement.
Schizophrenia is associated with a weighted average of 14.5 years of potential life lost according to a recent meta-analysis. This is partly explained by high rates of suicide and a high prevalence of non-psychiatric comorbidity (cardiovascular diseases, diabetes, cancers…). However, all these causes could not fully explain the loss of life expectancy in people suffering from schizophrenia. Life expectancy has been strongly correlated with telomere length (TL). Telomeres are noncoding structures consisting of DNA TTAGGG tandem repeats and associated proteins located at the end of the chromosomes. Their role is to help preserve genome stability by protecting chromosomal ends from the loss of genetic material. The progressive loss of telomeric material during cell divisions has led researchers to consider telomeres as molecular clocks that measure the number of divisions left until cellular death. The fact that both shorter telomeres and schizophrenia have been associated with a decrease in life expectancy has fueled the interest in the study of TL in schizophrenia. In this article, after a detailed review of the literature on the relationships between telomere length and schizophrenia, we discuss the different pathophysiological mechanisms which might explain this association. Based on this analysis, in the last part of the article we discuss potential research, therapeutic and prevention prospects. To date, the majority of the studies and meta-analyses found a decrease in TL in subjects with schizophrenia compared to control subjects. Conversely, all the studies exploring the TL in subjects suffering from first episode psychosis (FEP) have shown no significant difference from TL in control subjects. This suggests that excessive shortening of telomeres occurs during the course of the disease, thus it seems more probable that schizophrenia (or processes associated with it) affects TL rather than telomere erosion being a cause of the disorder. Several pathophysiological, non-mutually exclusive mechanisms have been proposed to explain the observed data. A first hypothesis to explain the acceleration of the physiological process of telomere erosion in schizophrenia is the activation of inflammation processes and oxidative stress as a consequence of schizophrenia per se. However, it seems more probable that reduced TL may be a result of cumulative exposure to chronic stress related to schizophrenia. Indeed, in healthy individuals a growing body of evidence has linked chronic stress to accelerated shortening of TL. This might explain why telomere erosion is too small to be detected in FEP patients who are younger and have a shorter duration of illness than subjects with schizophrenia. Based on these both explanations, telomere alterations may be considered as a biomarker of illness progression and might be useful for illness staging. Identifying processes associated with TL reduction might improve our understanding of the increased mortality and morbidity in schizophrenia, improve reliability of diagnosis, and hopefully suggest means for prevention and/or treatment. Treatments that prevent exposure and/or vulnerability to stressful life events that ameliorate schizophrenia may also prevent or decelerate telomere erosion. In this perspective, engaging subjects suffering from schizophrenia in a healthy diet and regular activity could be both promising strategies to protect telomere maintenance and improve health span at old age. In addition, the inflammatory process and oxidative stress involved in the physiopathology in at least a subgroup of subjects with schizophrenia could also be responsible for telomere erosion. Thus, an efficient anti-inflammatory therapeutic approach that targets these specific pathways could be of interest in this subgroup to limit telomere erosion. Mindfulness-based stress reduction (MBSR) therapies have been shown to reduce telomere erosion by increasing telomerase activity, although these psychological therapies should be used carefully in psychosis. Finally, advancing our understanding of the relationship between stress, inflammation and TL is of great interest for psychiatric research and for understanding stress effects in this population.
Increased telomerase activity in major depressive disorder with melancholic features: Possible role of pro-inflammatory cytokines and the brain-derived neurotrophic factor
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Citation Excerpt :
Some studies have concluded that the increase in pro-inflammatory cytokine levels in depressive patients without medication and during depressive episodes is negatively related to telomere length (Damjanovic et al., 2007; Wolkowitz et al., 2010; Wolkowitz et al., 2011). Lin, Epel, and Blackburn (2012) suggest that an excessive increase in inflammatory processes shortens cellular life and causes destruction, and this situation is regulated by a balancing system such as increased telomerase activity. Studies have found that levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1 (IL-1) are significantly higher in MDD patients than in healthy people (Dowlati et al., 2010; Howren et al., 2009; Irwin and Miller, 2007).
The biological mechanisms responsible for depression symptoms are not yet understood. For this reason, it is important to reveal the etiopathogenetic mechanisms in this disease. This study aims to compare the levels of pro-inflammatory cytokines, Brain-Derived Neurotrophic Factor (BDNF), and telomerase activity in patients with major depressive disorder (MDD) and healthy controls. Plasma BDNF, interleukin-6 (IL-6), IL-1beta, and Tumor Necrosis Factor-alpha (TNF-alpha) levels, and telomerase activity were measured in 39 patients with major depression and 39 healthy controls matched with patients in terms of age, gender, and education year. Plasma concentration of BDNF, IL-6 levels, and telomerase activity was significantly different between patients with MDD and healthy controls. Correlation analysis showed a positive trend between plasma BDNF levels and plasma IL-6 levels in patients with MDD with melancholic features. Furthermore, the path analysis results showed that the telomerase activity was indirectly affected by gender, IL-1β, IL-6, BDNF, and BMI, via the severity of depression and anxiety and MDD status as the mediators. Further studies are needed to examine the molecular mechanism of the telomerase activity and the role of BDNF and pro-inflammatory cytokines in the telomerase activation in MDD.
Deterioration of nuclear morphology and architecture: A hallmark of senescence and aging
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The metazoan nucleus is a highly structured organelle containing several well-defined sub-organelles. It is the largest organelle inside a cell taking up from one tenth to half of entire cell volume. This makes it one of the easiest organelles to identify and study under the microscope. Abnormalities in the nuclear morphology and architecture are commonly observed in an aged and senescent cell. For example, the nuclei enlarge, loose their shape, appear lobulated, harbour nuclear membrane invaginations, carry enlarged/fragmented nucleolus, loose heterochromatin, etc. In this review we discuss about the age-related changes in nuclear features and elaborate upon the molecular reasons driving the change. Many of these changes can be easily imaged under a microscope and analysed in silico. Thus, computational image analysis of nuclear features appears to be a promising tool to evaluate physiological age of a cell and offers to be a legitimate biomarker. It can be used to examine progression of age-related diseases and evaluate therapies.

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ReviewTelomeres and lifestyle factors: Roles in cellular aging

Abstract

Highlights

Section snippets

Perceived stress and adverse life events

Stress and stress-related psychiatric conditions

Telomere length and temperament

Dietary biomarkers and nutritional intake

Interventions

Possible mechanisms mediating relationships between life style factors and telomere length

Is telomerase activation a compensatory mechanism induced by telomere shortness?

Future directions

Conflict of interest

Biol. Psychiatry

Biol. Psychiatry

Brain Behav. Immun.

Lancet

Am. J. Clin. Nutr.

Transl. Res.

Am. J. Clin. Nutr.

Atherosclerosis

J. Nutr.

Am. J. Cardiol.

Lancet Oncol.

Psychoneuroendocrinology

Brain Behav. Immun.

Psychoneuroendocrinology

Biochem. Biophys. Res. Commun.

J. Psychosom. Res.

Trends Biochem. Sci.

J. Nutr.

J. Behav. Med.

Ageing Res. Rev.

Brain Behav. Immun.

Cell

FEBS Lett.

Am. J. Hum. Genet.

Am. J. Hum. Genet.

Accelerated telomere shortening in response to life stress

Proc. Natl. Acad. Sci. U.S.A.

Accelerated telomere erosion is associated with a declining immune function of caregivers of Alzheimer's disease patients

J. Immunol.

The effects of social status on biological aging as measured by white-blood-cell telomere length

Aging Cell

Educational attainment but not measures of current socioeconomic circumstances are associated with leukocyte telomere length in healthy older men and women

Brain Behav. Immun.

No association between socio-economic status and white blood cell telomere length

Aging Cell

Socioeconomic status and telomere length: the West of Scotland Coronary Prevention Study

J. Epidemiol. Community Health

Leukocyte telomere length is associated with disability in older U.S. Population

J. Am. Geriatr. Soc.

Older men with higher self-rated socioeconomic status have shorter telomeres

Age Ageing

Telomeres, sex, reactive oxygen species, and human cardiovascular aging

J. Mol. Med.

The longevity gender gap: are telomeres the explanation?

Sci. Aging Knowl. Environ.

Leukocyte telomeres are longer in african americans than in whites: the national heart, lung, and blood institute family heart study and the Bogalusa Heart Study

Aging Cell

Telomere shortening in formerly abused and never abused women

Biol. Res. Nurs.

Childhood adversities are associated with shorter telomere length at adult age both in individuals with an anxiety disorder and controls

PLoS One

Childhood adversity heightens the impact of later-life caregiving stress on telomere length and inflammation

Psychosom. Med.

Childhood Trauma Associated with Short Leukocyte Telomere Length in Posttraumatic Stress Disorder

Biol. Psychiatry

Life Stress, Emotional Health, and Mean Telomere Length in the European Prospective Investigation into Cancer (EPIC)-Norfolk Population Study

J. Gerontol. A. Biol. Sci. Med. Sci.

Review
Telomeres and lifestyle factors: Roles in cellular aging