Telomere length elongation after weight loss intervention in obese adults

doi:10.1016/j.ymgme.2016.04.003

Molecular Genetics and Metabolism

Volume 118, Issue 2, June 2016, Pages 138-142

https://doi.org/10.1016/j.ymgme.2016.04.003 Get rights and content

Highlights

•
Telomeres are considered markers of biological aging and aging-related diseases such as obesity.
•
The relationship between obesity and telomere complex functions is still not clear.
•
Weight loss, obtained by bioenteric intragastric balloon (BIB) for 6 months, is associated to telomere lengthening.
•
Telomere lengthening is more significant in those subjects with shortest telomeres at baseline.
•
A healthy life style promotes longevity and health.

Abstract

Introduction

Telomeres may be considered markers of biological aging, shorter telomere length is associated with some age-related diseases; in several studies short telomere length has also been associated to obesity in adults and adolescents. However the relationship between telomere complex functions and obesity is still not clear. Aim of the study was to assess telomere length (TL) in adults' obese subjects before and after weight loss obtained by placement of bioenteric intragastric balloon (BIB) for 6 months.

Methods

We enrolled 42 obese subjects before and after BIB placement as weight loss intervention. Blood samples were collected in order to obtain DNA from leukocyte to measure TL by quantitative PCR.

Results

Data were analyzed only in 37 subjects with complete data; all presented important body weight loss (124.06 ± 26.7 vs 105.40 ± 23.14, p < 0.001) and more interesting they presented a significant increase in TL (3.58 ± 0.83 vs 5.61 ± 3.29, p < 0.001). Moreover we observed a significant positive correlation between TL elongation and weight loss (r = 0.44, p = 0.007) as well as an inverse correlation between TL at baseline and TL elongation (r = − 0.35, p = 0.03).The predictors of TL elongation were once again weight loss and short TL at baseline (respectively p = 0.007 and p = 0.003).

Conclusions

Our study shows that weight loss is associated to telomere lengthening in a positive correlation: the greater weight loss the greater telomere lengthening; moreover telomere lengthening is more significant in those subjects with shortest telomeres at baseline.

Introduction

Telomeres consist of repetitive DNA sequences (TTAGGG) and are located at the ends of linear chromosomes. They stabilize and protect chromosomes from erosion and from being mistaken for double-strand DNA breaks [1]. During each cell division, telomeres shorten due to the “end-replication problem” that is the DNA polymerase's inability to fully replicate the 3′ end of chromosomes. In order to limit telomere attrition, germline and some somatic cells express telomerase, a reverse transcriptase that maintains telomere length by synthesizing new DNA sequences and adding them to the end of the chromosome [2]. Telomerase is an enzymatic protein complex including the telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC) used as a template to synthesize telomere DNA. When telomeres are too short, they signal the arrest of cell proliferation.

Telomere length (TL) varies between individuals and depends on TL at birth, reflecting a genetic inheritance and on the magnitude of telomere erosion from birth onwards [3] which depends on cell replication rate as well as on aging related exposure to agents that produce DNA damage. Oxidative stress and inflammation are major contributors to aging and aging related diseases and play an important role in telomere attrition [4], [5], [6]. It is well known that obesity is a state of chronic inflammation and great oxidative stress [7].

Available data on the relationship between obesity and TL in adults have shown controversial results; some studies reported an inverse association of TL with obesity [8], [9], [11], but others did not [12], [13] as also recently reported in a review and meta-analysis [14]. Very recently two studies showed a relationship between TL elongation with weight loss as well as with a great adherence to Mediterranean diet [15], [16]. To the best of our knowledge there are no data on the relation between weight loss obtained with BIB intervention and telomere length. The Bioenteric Intragastric Balloon is an alternative gastric restrictive procedure. It is a smooth, spherical, saline-filled, silicone elastomer with a radiopaque filling valve. It is inserted endoscopically and left inflated within the stomach. Insertion can be performed under conscious sedation. It is intended to reduce weight by limiting food consumption The BIB is not permanent and should be removed endoscopically after 6 months to reduce the risk of long-term complications, such as balloon perforation or migration and peptic ulceration [17]. The aim of this study was to assess the relationship between TL and weight loss by means of placement of Bioenteritc Intragastric Balloon (BIB) for 6 months in severe obese adults. We hypothesized that a greater weight loss would lead to a greater elongation of TL as has been previously observed in adult and adolescent studies [10], [15].

Section snippets

Study population

The study population included 42 severe obese adults undergoing BIB placement for six months as weight loss intervention together with a lifestyle education program supported by a multidisciplinary team of nutritionists and psychologists. In the present study, we present data before BIB placement and after removal at 6 months. Anthropometric measurements and blood samples were collected for each patients before BIB placement and after its removal, they also underwent an abdominal US in order to

Statistical analysis

As a preliminary analysis, one-sample Kolmogorov-Smirnov test was performed, in order to detect deviations from the normal distribution in the studied variables. The test did not allow in rejecting the null hypothesis for any of the variables studied, and therefore a normal distribution was assumed for the subsequent analyses.

We used the paired t-test for comparing the parameters at baseline and after 6 months, expressed as mean ± SD. With the present patient population, power analysis showed that

Results

The results were analyzed only in a series of 37 subjects having complete data available. Table 1 summarizes the general features of the 37 study subjects at baseline and after 6 months at BIB removal.

Baseline TL was not correlated with age nor with most of the metabolic variables investigated (BMI, total cholesterol, HDL-Cholesterol) (p > 0.1, data not shown). A significant correlation was detected between TL and serum triglycerides (r = − 0.36, P = 0.028).

As shown in Table 1, all subjects did

Discussion

In this study conducted on 37 obese subjects, a significant increase in TL after 6 months of weight loss intervention was observed. Our results are consistent with previously published studies on the benefits of a healthy lifestyle such as Mediterranean diet and weight loss on telomere length [15], [16], therefore in promoting health and longevity.

Interestingly, we observed that TL elongation correlated positively with the body weight loss indicating that the lengthening rate was most pronounced

Conflict of interest

The Authors declare no conflict of interest.

Informed consent

Written consent to participate in the study was obtained from each participant. The study protocol was performed in accordance with the ethical standards of the Declaration of Helsinki and the study protocol was approved by the Institutional Ethics Committee.

No specific funding was obtained.

Acknowledgments

The Authors acknowledge the essential collaboration provided by all professionals of the Obesity clinic, Internal Medicine ward and the Endoscopy group of the Nuovo Ospedale Civile S. Agostino-Estense, Modena, Italy.

References (33)

E.H. Blackburn
Switching and signaling at the telomere
Cell
(2001)
C.W. Greider et al.
Identification of a specific telomere terminal transferase activity in Tetrahymena extracts
Cell
(1985)
I. Shalev et al.
Stress and telomere biology: a lifespan perspective
Psychoneuroendocrinology
(2013)
J. Zhang et al.
Ageing and the telomere connection: an intimate relationship with inflammation
Ageing Res. Rev.
(2016 Jan)
M. Gardner et al.
Halcyon study team (2014). Gender and telomere length: systematic review and meta-analysis
Exp. Gerontol.
(2014 Mar)
J. Lin et al.
Greater endogenous estrogen exposure is associated with longer telomeres in postmenopausal women at risk for cognitive decline
Brain Res.
(Mar 16 2011)
T. von Zglinicki
Oxidative stress shortens telomeres
Trends Biochem. Sci.
(2002)
M.M. Ouellette et al.
Subsenescent telomere lengths in fibroblasts immortalized by limiting amounts of telomerase
J. Biol. Chem.
(2000)
M.T. Teixeira et al.
Telomere length homeostasis is achieved via a switch between telomerase- extendible and - nonextendible states
Cell
(2004)
Y.M. Lee et al.
Intragastric balloon significantly improves nonalcoholic fatty liver disease activity score in obese patients with nonalcoholic steatohepatitis: a pilot study
Gastrointest. Endosc.
(2012)

K.E. Herbert et al.

Angiotensin II-mediated oxidative DNA damage accelerates cellular senescence in cultured human vascular smooth muscle cells via telomere-dependent and independent pathways

Circ. Res.

(2008)

T. Minamino et al.

A crucial role for adipose tissue p53 in the regulation of insulin resistance

Nat. Med.

(2009)

K. Suzuki et al.

Relationship between obesity and serum markers of oxidative stress and inflammation in Japanese

Asian Pac. J. Cancer Prev.

(2003)

M. Lee et al.

Inverse association between adiposity and telomere length: the Fels longitudinal study

Am. J. Hum. Biol.

(2011)

O.T. Njajou et al.

Shorter telomeres are associated with obesity and weight gain in the elderly

Int. J. Obes. (Lond)

(2012)

Y. Cui et al.

Associations of leukocyte telomere length with body anthropometric indices and weight change in Chinese women

Obesity (Silver Spring)

(2013)

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Several studies indicated leukocyte telomere length (LTL) as a biomarker of multiple sclerosis (MS) evolution. This study aimed to investigate LTL in women with multiple sclerosis (MS) compared to that in healthy women (HW) across different reproductive phases, and to evaluate its relationship with MS activity.
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Telomeres play a critical role in maintaining cellular fate through tight regulation of cell division and DNA damage or repair. Over the years, it is established that biological ageing is defined by a gradual derangement in functionality, productivity, and robustness of biological processes. The link between telomeres and ageing is highlighted when derangement in telomere biology often leads to premature ageing and concomitant accompaniment of numerous age-associated diseases. Unfortunately, given that ageing is a biologically complicated intricacy, measures to reduce morbidity and improve longevity are still largely in the infancy stage. Recently, it was discovered that dietary habits and interventions might play a role in promoting successful healthy ageing. The intricate relationship between dietary components and its potential to protect the integrity of telomeres may provide unprecedented health benefits and protection against age-related pathologies. However, more focused prospective and follow-up studies with and without interventions are needed to unequivocally link dietary interventions with telomere maintenance in humans. This review aims to summarise recent findings that investigate the roles of nutrition on telomere biology and provide enough evidence for further studies to consider the topic of nutrigenomics and its contributions toward healthy ageing and concomitant strategy against age-associated diseases.
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Telomere shortening is insignificant in the stem cell compartment, where telomerase maintains telomere length (Flores et al., 2008), like in the germline. Unfortunately, most publications about “telomere length” investigate just circulating leucocyte telomere length (Epel et al., 2004), a convenient yet (in my opinion) largely meaningless parameter reflecting the amount of telomere shortening during hematopoietic stem cell differentiation, which might reflect inflammatory status but not aging (Carulli et al., 2016; Jongbloed et al., 2019; Laimer et al., 2016). Telomeres shorten rapidly during differentiation (Flores et al., 2008), and this is a highly effective mechanism to limit the tumorigenic potential of differentiating and expanding clones of cells.
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Telomere shortening is a natural process associated with aging although health conditions modulated by oxidative stress and inflammation, such as obesity, could accelerate the process. Given that age-related diseases are more prevalent in young obese patients, it is hypothesized that obesity could accelerate telomere shortening and in some way a state of premature aging [22]. On that basis, our study first sought to investigate relative TL in a cohort of obese patients awaiting bariatric surgery.
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Telomere length elongation after weight loss intervention in obese adults

Highlights

Abstract

Introduction

Methods

Results

Conclusions

Introduction

Section snippets

Study population

Statistical analysis

Results

Discussion

Conflict of interest

Informed consent

Acknowledgments

Cell

Cell

Psychoneuroendocrinology

Ageing Res. Rev.

Exp. Gerontol.

Brain Res.

Trends Biochem. Sci.

J. Biol. Chem.

Cell

Gastrointest. Endosc.

Angiotensin II-mediated oxidative DNA damage accelerates cellular senescence in cultured human vascular smooth muscle cells via telomere-dependent and independent pathways

Circ. Res.

A crucial role for adipose tissue p53 in the regulation of insulin resistance

Nat. Med.

Relationship between obesity and serum markers of oxidative stress and inflammation in Japanese

Asian Pac. J. Cancer Prev.

Inverse association between adiposity and telomere length: the Fels longitudinal study

Am. J. Hum. Biol.

Shorter telomeres are associated with obesity and weight gain in the elderly

Int. J. Obes. (Lond)

Associations of leukocyte telomere length with body anthropometric indices and weight change in Chinese women

Obesity (Silver Spring)