Telomeres, Nutrition and Mortality: Risk Factors for the Rate of Telomere Length Decline and the Associations Between Telomere Length, Nutrition and Mortality

Introduction: Telomeres are nucleoprotein structures located at the ends of eukaryotic chromosomes, thought to protect the DNA from damage. As a person experiences stressors, harmful exposures, and other diseases throughout their life, telomeres are thought to become damaged and their length shortened, decreasing their ability to protect the DNA. Nutrition is an important aspect of healthy aging. Preservation of telomere length (TL) is thought to be one of the mechanisms by which good nutrition can delay or prevent the development of chronic disease and death. Recent evidence of preservation of TL with good nutrition is promising. Thus, the aim of this dissertation is to study the relationship of TL with nutrition and mortality, which will be accomplished through three distinct, but ancillary aims. The first aim of this research is to examine rates of age-related TL change and evaluate variability in the rate by gender, chronic stress, and chronic diseases. The second aim is to comprehensively examine the linear associations between different macro- and micro-nutrients and healthy eating and TL. The third aim is to assess the associations of TL with survival and lifespan. Methods: For the first and second study aim, cross-sectional data on individuals, aged ≥ 20 years with a TL measurement available, were included from the National Health and Nutrition Examination Survey, years 1999-2002. Crude and adjusted linear regression models were used to estimate the rate of decline in TL across 10-year age categories, and any variations in the decline with respect to sex, measure of chronic stress, and presence of chronic diseases. To evaluate the associations between TL and a variety of macro- and micro-nutrients, and healthy eating, multivariate linear regression models using energy-adjusted nutrients were implemented. For the third aim of the study, data on 328 elderly (oldest-old) men from the Zutphen (The Netherlands) and Cretan (Greece) Elderly Study, with available TL measurement in 2000 were included.Follow-up for vital status was available until September 2015. Kaplan-Meier survival estimation assessed differences in survival between men with short and long TL. Univariate and multivariable Cox proportional hazard models assessed the associations of TL (standardized continuous measure) on survival. Linear regression models assessed the relation of TL on age at death. Results: In an adjusted model, the population rate of decline in TL with age was consistent and linear for only three age categories: 20-29 (β=-0.0196, 95% CI: -0.0360, -0.0032), 50-59 (β=-0.0200, 95% CI: -0.0326, -0.0074) and 70-79 (β=-0.0164, 95% CI: -0.0318, -0.0010) years. The population rate of decline in TL with age was significantly greater for males and those with high allostatic load (a measure of chronic stress) and a history of comorbidities. When the population rate of decline in TL was analyzed by gender in 10-year age bins, a fairly consistent yet statistically non-significant decline for males was observed; however, a trough in the rate was observed for females in the age categories 20-29 years (β=-0.0283, 95% CI: -0.0468, -0.0099) and 50-59 years (β=-0.0216, 95% CI: -0.0396, -0.0036). To further elucidate the gender difference observed in the primary analyses, secondary analyses were conducted with reproductive and hormonal status; a significant inverse association was found between TL and parity, menopause, and age at menopause. In a linear regression model to study associations between TL and nutrients, adjusted for demographics and health-related behaviors, of the macronutrients examined, total fat (β= -83.24, 95% CI: -153.31, -13.17), mono-unsaturated (β= -107.40, 95% CI: -175.39, -39.40) and poly-unsaturated fatty acids (β=-54.01, 95% CI: -99.81, -8.19) were inversely associated with TL. Of the micro-nutrients examined, potassium was the only element (β= 90.17, 95% CI: 7.54, 172.79) and riboflavin or Vitamin B2 (β= 85.04, 95% CI: 1.53, 168.54) was the only vitamin that was significantly associated with TL in fully adjusted models. However, Vitamin A, B12, and E were inversely associated with TL in energy adjusted models. After adjustment for total calorie, demographic, and health-related behaviors, the overall healthy eating index (HEI) score was positively associated with TL (β= 3.42, 95% CI: 0.29, 6.53, p-value=0.033); every unit increase in HEI score increased the TL by 3.42 base pairs. In the mortality study, all but nine men were deceased by the end of the study period. TL was not related to socio-demographic factors, lifestyle factors and prevalent chronic diseases. Kaplan-Meier survival analysis did not show statistically significant differences in all-cause or cardiovascular mortality between long and short TL groups. In Cox proportional hazards models, long TL was not associated with all-cause (HR: 0.90, 95%CI: 0.68 - 1.17) and cardiovascular mortality (HR: 0.96, 95%CI 0.62 - 1.50). In linear regression models, TL was not a significant predictor of age at death. Findings were also not significant when analyzed separately for the Zutphen and Cretan cohort. Conclusions: TL was shorter with increasing age and this decline was modified by gender, chronic stress and comorbidities; individuals with chronic morbidity and/or chronic stress and females in their twenties and fifties experienced greater decline. Female reproductive factors, i.e., parity and menopause, were associated with TL. Certain nutrients, as well as healthy eating in general, are associated with preservation of TL. Health gains associated with telomere preservation could potentially be achieved relatively easily through promotion of healthy and adequate diets. Finally, the lack of associations of TL with mortality and lifespan in the elderly men from Zutphen and Crete is consistent with previous literature

Decline in Telomere Length by Age and Effect Modification by Gender, Allostatic Load and Comorbidities in National Health and Nutrition Examination Survey (1999-2002)

Background: This study aims to assess the decline in telomere length (TL) with age and evaluate effect modification by gender, chronic stress, and comorbidity in a representative sample of the US population. Methods: Cross-sectional data on 7826 adults with a TL measurement, were included from the National Health and Nutrition Examination Survey, years 1999–2002. The population rate of decline in TL across 10-year age categories was estimated using crude and adjusted regression. Results: In an adjusted model, the population rate of decline in TL with age was consistent and linear for only three age categories: 20–29 (β = -0.0172, 95% CI: -0.0342, -0.0002), 50–59 (β = -0.0182, 95% CI: -0.0311, -0.0054) and 70–79 (β = -0.0170, 95% CI: -0.0329, -0.0011) years. The population rate of decline in TL with age was significantly greater for males and those with high allostatic load and a history of comorbidities. When the population rate of decline in TL was analyzed by gender in 10-year age bins, a fairly consistent yet statistically non-significant decline for males was observed; however, a trough in the rate was observed for females in the age categories 20–29 years (β = -0.0284, 95% CI: -0.0464, -0.0103) and 50–59 years (β = -0.0211, 95% CI: -0.0391, -0.0032). To further elucidate the gender difference observed in the primary analyses, secondary analyses were conducted with reproductive and hormonal status; a significant inverse association was found between TL and parity, menopause, and age at menopause. Conclusions: TL was shorter with increasing age and this decline was modified by gender, chronic stress and comorbidities; individuals with chronic morbidity and/or chronic stress and females in their twenties and fifties experienced greater decline. Female reproductive factors, i.e., parity and menopause, were associated with TL

Practice and Lived Experience of Menstrual Exiles (Chhaupadi) among Adolescent Girls in Far Western Nepal. December 2018

Background: Menstrual exile, also known as Chhaupadi, is a tradition of “untouchability” in far-western Nepal. Forbidden from touching other people and objects, women and girls are required to live away from the community, typically in a livestock shed, during menstruation. We assessed the lived experiences of Chhaupadi among Nepalese adolescent girls in the far-western Achham district of Nepal, observed the safety and sanitation of their living spaces during Chhaupadi, and assessed the perceptions of local adult stakeholders towards the practice of Chhaupadi. Methods: We collected data from 107 adolescent girls using a self-administered survey in two local schools in Achham. We also conducted a focus group discussion with seven girls, held key informant interviews, and observed the girls’ living spaces during Chhaupadi, using a checklist. Descriptive statistics of the quantitative survey and thematic analyses of qualitative interviews are presented. Results: The majority of the girls (n = 77, 72%) practiced exile, or Chhaupadi, during their menstruation, including 3 (4%) exiled to traditional Chhau sheds, 63 (82%) to livestock sheds, and 11 (14%) to courtyards outside their home. The remaining girls (n = 30, 28%) stayed inside the house, yet practiced some form of menstrual taboos. Of the 77 observed living spaces where the girls stayed during exile, only 30% (n = 23) had a toilet facility. Most exiled girls (97.4%) were restricted from eating dairy products. Participants reported having various psychological problems, including lonliness and difficulty sleeping while practicing Chhaupadi. Three of the girls were physically abused; nine were bitten by a snake. Notably high proportions of the living spaces lacked ventilation/windows (n = 20, 26%), electricity (n = 29, 38%), toilets (n = 54, 70%) and a warm blanket and mattress for sleeping (n = 29, 38%). Our qualitative findings supported our quantitative results. Conclusions: Chhaupadi has been condemned by human rights organizations. While the government has banned the practice, implementation on the ban is proceeding slowly, especially in far-western Nepal. Thus, as a temporary measure, public health professionals must work towards promoting the health and safety of Nepalese women and girls still practicing Chhaupadi

Burden of Diabetes and Prediabetes in Nepal: A Systematic Review and Meta-Analysis

Unhealthy behaviors, such as energy-dense food choices and a sedentary lifestyle, both of which are established risk factors for diabetes, are common and increasing among Nepalese adults. Previous studies have reported a wide variation in the prevalence of prediabetes and diabetes in Nepal, and thus a more reliable pooled estimate is needed. Furthermore, Nepal underwent federalization in 2015, and the province-specific prevalence, which is necessary for the de novo provincial government to formulate local health policies, is lacking. This study aims to provide a comprehensive summary of the current literature on various aspects of diabetes in Nepal, i.e., the prevalence of prediabetes and diabetes as well as of the awareness, treatment, and control of diabetes in Nepal.This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched three electronic databases-PubMed, Scopus, and Web of Science-using a comprehensive search strategy to identify eligible studies published up to April 2, 2020. Data on prevalence estimates of prediabetes and diabetes were extracted and pooled in a meta-analysis using a random effect model. Subgroup analyses and meta-regression were conducted to assess heterogeneity across the studies. The quality of included studies was assessed using the New Castle-Ottawa scale.We included 14 eligible studies that comprised a total of 44,129 participants and 3517 diabetes cases. Half of the included studies had good quality. Overall, the prevalence of prediabetes and diabetes was 9.2% (95% CI 6.6-12.6%) and 8.5% (95% CI 6.9-10.4%), respectively. Among the participants with diabetes, only 52.7% (95% CI 41.7-63.4%) were aware of their diabetes status, and 45.3% (95% CI 31.6-59.8%) were taking antidiabetic medications. Nearly one-third of those under antidiabetic treatment (36.7%; 95% CI 21.3-53.3%) had their blood glucose under control. The prevalence of prediabetes and diabetes gradually increased with increasing age and was more prevalent among males and urban residents. There was a wide variation in diabetes prevalence across the provinces in Nepal, the lowest 2% in Province 6 to the highest 10% in Province 3 and Province 4.The prevalence of prediabetes and diabetes was high in Nepal, while its awareness, treatment, and control were low. Our findings call for urgent nationwide public health action in Nepal

Nutritional Assessment of Community-Dwelling Older Adults in Rural Nepal

Demographic transition in Nepal, like in many developing countries, has resulted in a burgeoning elderly population whose health status is not currently monitored. One pillar of health is adequate nutrition. Yet, little is known about the nutritional health status of the elderly in Nepal. The financial, material, and personnel limitations in Nepal’s health delivery services necessitate health screening instruments that require minimal clinical staff and resources. To our knowledge, no such nutritional assessment tool has been validated in Nepal. Therefore, our aims are two-fold: To assess the nutritional status of the elderly population in one typical Nepali village, Okharpauwa, in Nuwakot District, Nepal; and concurrently, to validate the Mini Nutritional Assessment (MNA) tool...(See full text for complete abstract

Health Care Utilization and Health Care Expenditure of Nepali Older Adults

Introduction: Aging is associated with multiple chronic conditions. In older age, health needs and demand for health services utilization increase. There are limited data in Nepal on the health care utilization as well as health care costs among the elderly population. Therefore, it is imperative to explore the factors hindering access to health care among Nepalese older adults. Our study aims to explore the health care utilization and expenditure among Nepali older adults.Method: A community-based cross-sectional survey was conducted among 401 older adults residing in Pokhara Lekhnath metropolitan of Nepal. The survey tool was adapted from the Study on Global Aging and Adult Health (SAGE)'s questions on “Health Care Utilization.” The predictors of health care utilization were assessed in binary logistic regression models.Results: Study participants, mean (±SD) age 70.2 (±8.0) years, had various preexisting conditions such as hypertension (37.7 %), gastritis (28.4 %), asthma (25.4 %), and arthritis (23.4%) reported in the past 12 months but only 70% visited a health facility. A notable proportion (30%) of participants didn't utilize health services despite having a health problem. The utilization of out-patient and in-patient health services were 87.5 and 14.6% respectively. The use of private health facilities (56.4%) was high compared to the use of government health facilities (35.7%). Privileged ethnicity, living with a partner, higher annual income, knowledge of social insurance, and multi-morbidity were associated with higher odds of utilizing health services. Participants of privileged ethnicity, with higher household income, attending private health facility, and having multi-morbidities had significantly higher out of pocket health expenditures.Conclusions: A notable proportion of elderly participants did not utilize health services despite having a health problem. The public health system must develop effective strategies to attract this segment of the society. High dependency on private health facilities, as noted in the study, will only lead toward higher out of pocket health expenditures. The health benefits of regular health screenings must be disseminated among the elderly population. Developing quality and affordable health care services for older adults to ensure equity in accessibility will be a major task for the public health system in Nepal

Prevalence of non-communicable chronic conditions, multimorbidity and its correlates among older adults in rural Nepal : a cross-sectional study

Objectives This study's objectives were to estimate the prevalence of major non-communicable conditions and multimorbidity among older adults in rural Nepal and examine the associated socioeconomic and behavioural risk factors. Design This was a community-based cross-sectional study conducted between January and April 2018. Setting Rural municipalities of Sunsari and Morang districts in eastern Nepal. Participants 794 older Nepalese adults, 60 years and older, were recruited using a multistage cluster sampling approach. Primary outcome measure(s) Prevalence of four major non-communicable chronic conditions (osteoarthritis, cardiovascular disease, diabetes and chronic obstructive pulmonary disease (COPD) and multimorbidity. Results Almost half (48.9%: men 45.3%; women 52.4%) of the participants had at least one of four non-communicable chronic conditions, and 14.6% (men 12.5%; women 16.8%) had two or more conditions. The prevalence of individual conditions included: osteoarthritis-41.7% (men 37.5%; women 45.9%), cardiovascular disease-2.4% (men 2.8%; women 2.0%), diabetes-5.3% (men 6.0%; women 4.6%) and COPD-15.4% (men 13.3%; women 17.5%). In the adjusted model, older adults aged 70-79 years (adjusted OR (AOR): 1.62; 95% CI: 1.04 to 2.54), those from Madhesi and other ethnic groups (AOR: 1.08; 95% CI: 1.02 to 1.72), without a history of alcohol drinking (AOR: 1.53; 95% CI: 1.18 to 2.01) and those physically inactive (AOR: 5.02; 95% CI: 1.47 to 17.17) had significantly higher odds of multimorbidity. Conclusions This study found one in seven study participants had multimorbidity. The prevalence of multimorbidity and associated socioeconomic and behavioural correlates need to be addressed by integrating social programmes with health prevention and management at multiple levels. Moreover, a longitudinal study is suggested to understand the temporal relationship between lifestyle predictors and multimorbidity among older Nepalese adults

Geographic and Socio-Economic Variation in Markers of Indoor air Pollution in Nepal: Evidence From a Nationally-Representative Data

Background: In low-income countries such as Nepal, indoor air pollution (IAP), generated by the indoor burning of biomass fuels, is the top-fourth risk factor driving overall morbidity and mortality. We present the first assessment of geographic and socio-economic determinants of the markers of IAP (specifically fuel types, cooking practices, and indoor smoking) in a nationally-representative sample of Nepalese households. Methods: Household level data on 11,040 households, obtained from the 2016 Nepal Demographic and Health Survey, were analyzed.Binary logistic regression analyses were conducted to assess the use of fuel types, indoor cooking practices, indoor smoking and IAP with respect to socio-economic indicators and geographic location of the household. Results: More than 80% of the households had at least one marker of IAP: 66% of the household used unclean fuel, 45% did not have a separate kitchen to cook in, and 43% had indoor smoking. In adjusted binary logistic regression, female and educational attainment of household’s head favored cleaner indoor environment, i.e., using clean fuel, cooking in a separate kitchen, not smoking indoors, and subsequently no indoor pollution. In contrast, households belonging to lower wealth quintile and rural areas did not favor a cleaner indoor environment. Households in Province 2, compared to Province 1, were particularly prone to indoor pollution due to unclean fuel use, no separate kitchen to cook in, and smoking indoors. Most of the districts had a high burden of IAP and its markers.Conclusions: Fuel choice and clean indoor practices are dependent on household socio-economic status. The geographical disparity in the distribution of markers of IAP calls for public health interventions targeting households that are poor and located in rural areas

The burden and correlates of multiple cardiometabolic risk factors in a semi-urban population of Nepal:a community-based cross-sectional study

This study assessed the burden and correlates of three cardiometabolic risk factors, (hypertension, diabetes, and overweight/obesity), and their possible clustering patterns in a semi-urban population of Nepal. Data were obtained from a community-based management of non-communicable disease in Nepal (COBIN) Wave II study, which included 2,310 adults aged 25-64 years in a semi-urban area of Pokhara Metropolitan City of Nepal, using the World Health Organization-STEPS questionnaire. Unadjusted and adjusted binary logistic regression models were used to study the correlates of the individual risk factors and their clustering. The prevalence of hypertension, diabetes, and overweight/obesity was 34.5%, 11.7%, and 52.9%, respectively. In total, 68.2% of the participants had at least one risk factor and many participants had two risks in combination: 6.8% for 'hypertension and diabetes', 7.4% for 'diabetes and overweight/obesity' and 21.4% for 'hypertension and overweight/obesity'. In total, 4.7% had all three risk factors. Janajati ethnicity (1.4-2.1 times), male gender (1.5 times) and family history of diabetes (1.4-3.4 times) were associated with presence of individual risk factors. Similarly, Janajati ethnicity (aOR: 4.31, 95% CI: 2.53-7.32), current smoking (aOR: 4.81, 95% CI: 2.27-10.21), and family history of diabetes (aOR: 4.60, 95% CI: 2.67-7.91) were associated with presence of all three risk factors. Our study found a high prevalence of all single and combined cardiometabolic risk factors in Nepal. It underlines the need to manage risk factors in aggregate and plan prevention activities targeting multiple risk factors

Perceived change in tobacco use and its associated factors among older adults residing in Rohingya refugee camps during the COVID-19 pandemic in Bangladesh

This study explored the perceived change in tobacco use during the COVID-19 pandemic and its associated factors among older adults residing in Rohingya refugee camps, also referred to as Forcibly Displaced Myanmar Nationals in Bangladesh. The study followed a cross-sectional design and was conducted in October 2020 among 416 older adults aged 60 years and above. A purposive sampling technique was applied to identify eligible participants, and face-to-face interviews were conducted using a pre-tested semi-structured questionnaire to collect the data. Participants were asked if they noted any change in their tobacco use patterns (smoking or smokeless tobacco) during the COVID-19 pandemic compared to pre-pandemic. Binary logistic regression models determined the factors associated with the perceived change in tobacco use. More than one in five participants (22.4%) were current tobacco users, of whom 40.8% reported a perceived increase in tobacco use during the COVID-19 pandemic. Adjusted analysis revealed that participants who were concerned about COVID-19 had significantly (p < 0.05) lower odds of perceived increase in tobacco use (aOR = 0.22, 95% CI: 0.06–0.73), while older adults who were overwhelmed by COVID-19 (aOR = 0.26, 95% CI: 0.06–1.18) and communicated less frequently with others during the pandemic than before (aOR = 0.19, 95% CI: 0.03–1.20) had marginally significantly (p < 0.1) lower odds of perceived increase in tobacco use during this pandemic. Relevant stakeholders, policymakers, and practitioners need to focus on strengthening awareness-raising initiatives as part of an emergency preparedness plan to control tobacco use during such a crisis period