35 Integration of physical activity, genes and health

Ajeet Jaiswal

epgp books

 

 

 

Contents

 

1.             Introduction:

2.            Genetic and Physical activity

3.            Physical activity: Role of Genes and the Environment

4.            Genetic and Environmental Influences on Leisure-Time Physical Activity

5.            Health Benefits of Physical Activity

6.            Physical Activity or Physical Fitness?

7.            How much Physical Activity is Enough?

8.            How does Physical Activity and Fitness Lead to Improved Health Outcomes?

9.            Physical inactivity—a modifiable risk factor

10.          Evidence for a role of specific genes

11.           Summary

 

Learning Objectives:

  • The course provides an introduction to the field of Integration of Physical Activity, Genes and Health
  • It includes the Basic concept of Genes and the Environment on Physical activity, Health Benefits of Physical Activity and Physical Activity or Physical Fitness
  • The study of this module enables the students at postgraduate level to understand, How much Physical Activity is Enough and How does Physical Activity and Fitness Lead to Improved Health Outcomes

    1. Introduction

 

Over 2,500 year ago, Hippocrates noted the potential health benefits of daily exercise of moderate intensity such as a simple walk. In the last six decades, and since the landmark work by Morris and coworkers (Morris et.al, 1980), the plethora of epidemiologic evidence accumulated supports unequivocally an inverse, independent, and graded association between physical activity, health, and cardiovascular and overall mortality in apparently healthy individuals (Paffenbarger et.al, 1986; Tanasescu et.al, 1994; Kujala et.al, 1998; Martinez-Gonzalez et.al, 2001; Mora et.al, 2007) and in patients with documented cardiovascular disease (Bouchard and Shephard, 1994).

 

The exercise-induced health benefits are in part related to favorable modulations of health risk factors that have been observed with increased physical activity patterns or structured exercise programs (Mora et.al, 2007). Most recently the discovery that skeletal muscles are capable of communicating with other tissues by the release of myokines into the circulation aids to our understanding of the exercise-induced health benefits on the molecular level.

 

More specifically, Bostrom et.al, (2012) identified a new hormone irisin, named after the ancient Greek goddess of the rainbow and messenger of the Olympian gods. Irisin is released into the circulation by the skeletal muscle during exercise and triggers the transformation of white fat cells to cells that behave similar to brown fat cells (brown-in-white or brite cells). Moreover, mice engineered to express high irisin levels in blood were resistant to obesity and diabetes. These findings provide a mechanistic explanation for the protection exercise offers against metabolic diseases and perhaps a network of other chronic human diseases (Bostrom et.al, 2012).

 

Epidemiological studies have revealed that physical activity can reduce risks for preventing several chronic diseases and even reducing mortality (Morris et.al, 1980; Paffenbarger et.al, 1986; Tanasescu et.al, 1994; Kujala et.al, 1998; Mora et.al, 2007). However, a substantial proportion of individuals, especially those living in the most developed countries, do not participate in sufficient physical activities and thus fail to gain the subsequent health benefits (Pratt et.al, 1999; Martinez-Gonzalez et.al, 2001). If we are to understand why some subjects fail to engage in regular physical activity in leisure time, then we need to clarify which factors underlie individual differences in physical activity behavior.

 

It is known that many different factors play a role in leisure-time physical activity behavior. Leisure-time physical activity level may partly be determined on the basis of personal traits, needs, and interests and partly on external factors such as environment and availability factors (Bouchard and Shephard, 1994; Boomsma et.al, 2002). Some of these factors may make it easier or harder for certain individuals to achieve high levels of physical activity.

 

However, it is important to remember that environmental and genetic factors always work in conjunction. In the last decades, serious attempts have been made to clarify the role of different factors in physical activity behavior. Studies have concentrated on the correlates (i.e., factors associated with physical activity) and the determinants of physical activity (i.e., factors associated with a causal relationship). No clear consensus has been achieved, although several factors such as age, sex, previous physical activity, self-efficacy, and health status do seem to be associated with current physical activity level (Bauman, et.al, 2012).

 

2.Genetic and Physical activity

 

Genetic studies are one of the new areas of physical activity research. This is logical because individual’s genetic characteristics seem to be a possible determinant of physical activity (Bauman, et.al, 2012), and advances in genetic technologies permit identification of individual genes or gene systems associated with a trait such as physical activity. These studies have attempted to determine the genetic architecture of factors contributing to an individual’s propensity to be physically active. This includes estimating the overall role of genetic factors (in contrast to all non-genetic factors). If genetic factors are shown to be relevant, work is done to identify the genes and the mode of action of the genes in physical activity. The overall contribution of genetic factors to variation in physical activity is often examined by conducting twin studies.

 

Twin study designs are popular in behavioral genetics, as they provide an opportunity to disentangle the effects of genes from those of the environment (Boomsma, et.al, 2002; Dongen, et.al, 2012). In addition to genetics, motivation is a personal characteristic that also may be one of the key factors to help understand why some people spend their leisure time undertaking physical activity. This may be the reason why motives have been widely studied.

 

Although there are cross-sectional studies examining the associations between the genetic and environmental influences, motives, and leisure-time physical activity, longitudinal studies have been less frequently conducted. However, the advantages of longitudinal study designs are that causal associations can be better revealed and that the true effects of aging may be demonstrated. To date, little is also known about whether the motives for physical activity change over the life course. Another poorly characterized area is the difference in motivational factors between active and inactive individuals.

 

The recent findings on genetic and environmental influences on the longitudinal changes of leisure-time physical activity behavior as revealed in the twin studies: first, from adolescence to young adulthood and, second, over a 6-year follow-up period in adulthood. Furthermore, the motives for leisure-time physical activity among consistently physically active and inactive people from the twin studies (Aaltonen, 2013).

 

Physical activity has been defined to be body movements produced by the skeletal muscles, which cause a substantial increase in energy demands over resting energy expenditure (Caspersen, et.al, 1985). However, the term physical activity is often used interchangeably with the terms exercise or sports although that is not correct or recommended (Caspersen, et.al, 1985). The choice of term (physical activity, exercise, or sports) may impact the results of the genetic analyses and motivational studies.

 

3.Physical activity: Role of Genes and the Environment

 

Physical inactivity is a major risk factor for complex metabolic diseases such as obesity, diabetes, and hypertension (US Department of Health & Human Services, 1996). Traditionally, these morbidities have been the specific burden of adulthood, but their diagnosis in the young is now increasing (Moran, 1999; Sinaiko, et.al, 2001). Some have suggested that, as is true for adults (Caspersen, et.al, 2000), children are becoming less physically active and that changes in lifestyle, including declining levels of physical activity, may help explain why childhood metabolic diseases are becoming more common. Thus, because physical activity appears to track from childhood through to adulthood (Telama et.al, 1997; Tammelin, 2003), and because genetic effects are potentially more discernable at a young age, comprehending the antecedents of physical inactivity in the young is important for the prevention of inactivity and related disease at all ages.

 

Some investigators have proposed that the behavior of physical activity is primarily determined by genetic factors (Tammelin, 2003). Indeed, several studies have shown familial aggregation of physical activity (Caspersen, et.al, 2000), which suggests the potential importance of genetic factors in mediating this behavior.

 

4.Genetic and Environmental Influences on Leisure-Time Physical Activity

 

In quantitative genetic modeling, physical activity is assumed to be made up of genetic and environmental contributions. Environmental influences can be divided into shared environmental influences, representing the effects of environmental factors shared, for example, by the co-twins in a pair. Specific environmental influences represent unique environmental influences and specific environmental influences result in differences between the co-twins of a pair (Rijsdijk and Sham, 2002). A number of twin studies using the quantitative genetic modeling have shown that genetic influences play an important role in explaining individual differences in leisure-time physical activity (Kaprio, 1981). However, the different studies have found very different patterns. They found that the heritability of exercise participation ranged from 48% to 71% (Stubbe, 2006). As this investigation indicates, it is clear that there is heterogeneity in the results of studies related to genetic influences on leisure-time physical activity. It can be assumed that a significant proportion of the heterogeneity may derive not only from changes in the genetic contribution to this trait indifferent aged individuals but also from culture specific, sex-specific, and period-specific effects.

 

Physical activity assessment methods may also have an influence on the heterogeneity of results. Heritability is always assessed at a particular time and age, and above all, heritability is an estimate of the genetic influences to individual differences on a population level. Longitudinal study designs are needed to reveal the age specific genetic influences on leisure-time physical activity. Simonen et al, (2004) reported change across the lifespan in heritability estimates for leisure-time physical activity in adult male twin pairs. A recent comparative study in twins revealed also age-related changes in heritability (Vink, et al, 2011). Earlier studies have also reported a shift between genetic and environmental influences in the time periods between childhood and adolescence and between adolescence and young adulthood, although at different times in different studies and in different directions.

 

In boys, genetic influences on leisure-time exercise behavior were fluctuating from age of 7 years to age of 12 years, while in girls genetic influences were more stable (Huppertz, et al, 2012). In this study, shared environmental influences mainly explained the largest part of the variance in leisure-time exercise behavior between childhood and early adolescence. The decline in the heritability estimate was noted in longitudinal studies by vanderaa et al. (2010). Genetic influences on leisure time physical activity declined from early adolescence to late adolescence in both sexes in twins and decline was also seen during a 4-year follow up among young men in their twenties (vanderaa et al. (2010). In contrast to these studies, Stubbe et al. (2005) found in their longitudinal study that between the age of 13 and the age of 16 years genetic influences were not important, whereas between the age of 19 and the age of 20 years genetic influences largely explained the individual differences in leisure-time sports participation.

 

5.Health Benefits of Physical Activity

 

Physical inactivity is a modifiable risk factor for cardiovascular disease and a widening variety of other chronic diseases, including diabetes mellitus, cancer (colon and breast), obesity, hypertension, bone and joint diseases (osteoporosis and osteoarthritis), and depression (Bauman, 2012). There is incontrovertible evidence that regular physical activity contributes to the primary and secondary prevention of several chronic diseases and is associated with a reduced risk of premature death. There appears to be a graded linear relation between the volume of physical activity and health status, such that the most physically active people are at the lowest risk.

 

However, the greatest improvements in health status are seen when people who are least fit become physically active. The current activity guidelines promoted by Health Canada appear to be sufficient to reduce health risk. People who engage in exercise at levels above those recommended in the guidelines are likely to gain further health benefits. Health promotion programs should target people of all ages, since the risk of chronic disease starts in childhood and increases with age.

 

6.Physical Activity or Physical Fitness?

 

Physical fitness refers to a physiologic state of well-being that allows one to meet the demands of daily living or that provides the basis for sport performance, or both. Health-related physical fitness involves the components of physical fitness related to health status, including cardiovascular fitness, musculoskeletal fitness, body composition and metabolism. In large epidemiologic investigations, physical activity and physical fitness are often used interchangeably, with fitness commonly being treated as a more accurate (albeit indirect) measure of physical activity than self-report (Williams, 2001).

 

Physical fitness appears to be similar to physical activity in its relation to morbidity and mortality (Booth, 2012) but is more strongly predictive of health outcomes than physical activity Williams, 2001). Most analyses have shown a reduction of at least 50% in mortality among highly fit people compared with low-fit people.

 

Nonetheless, both physical activity and fitness are strong predictors of risk of death. To obtain accurate estimates of physical activity, many fitness consultants rely on primary (criterion and “gold”) standards for the measurement of energy expenditure, such as direct observation of movement or, in the laboratory, the doubly labelled water technique or indirect calorimetry (Sirard, 2001). On a practical basis, however, measures of physical activity and energy expenditure are obtained by using heart rate monitors and motion sensors (pedometers and accelerometers). The assessment of physical fitness is often not feasible or practical in large population-based investigations. Fortunately such studies have consistently shown an inverse gradient of health risk across self-reported physical activity groups. From a public health perspective, Blair et al, (2001), have argued that it is preferable to encourage people to become more physically active rather than to become physically fit, since, as they stated, sedentary people will likely achieve the latter if they do the former.

 

7.How much Physical Activity is Enough?

 

It is apparent that physical activity is essential in the prevention of chronic disease and premature death. However, doubt remains over the optimal “volume” (frequency, duration and intensity of exercise) and the minimum volume for health benefits, in particular the effects of intensity (e.g., moderate vs vigorous) on health status. There is evidence that intensity of physical activity is inversely and linearly associated with mortality. Early work by Paffenbarger et al, (1986) revealed that regular physical activity (expending > 2000 kcal [8400 kJ] per week) was associated with an average increase in life expectancy of 1 to 2 years by the age of 80 and that the benefits were linear even at lower levels of energy expenditure.

 

Subsequent studies have shown that an average energy expenditure of about 1000 kcal (4200 kJ) per week is associated with a 20%–30% reduction in all-cause mortality. Currently, most health and fitness organizations and professionals advocate a minimum volume of exercise that expends 1000 kcal (4200 kJ) per week and acknowledge the added benefits of higher energy expenditures.

 

Recently, investigators have postulated that even lower levels of weekly energy expenditure may be associated with health benefits. A volume of exercise that is about half of what is currently recommended may be sufficient (Lee and Skerrett, 2001) particularly for people who are extremely deconditioned or are frail and elderly (Blair et.al, 2001), Future research is required to determine whether expending as little as 500 kcal (2100 kJ) per week offers health benefits. If so, then previously sedentary people may be more likely to engage in physical activity and maintain an active lifestyle.

 

The dose–response relation between physical activity and health status outlined above generally relates to cardiovascular disease and premature death from any cause. However, the same may hold true for other activity-associated health benefits. For instance, as mentioned earlier, moderately intense levels of exercise (≥5.5 METs for at least 40 minutes per week) and of cardiovascular fitness (> 31 mL oxygen per kilogram per minute) are effective preventive strategies against type 2 diabetes. In patients with type 2 diabetes, walking more than 2 hours per week has also been shown to reduce the risk of premature death. With respect to cancer, a review of the literature revealed that moderate physical activity (> 4.5 METs) for about 30–60 minutes per day had a greater protective effect against colon and breast cancer than activities of low intensity. The greatest benefit for reducing the incidence of breast cancer was observed among women who engaged in 7 or more hours of moderate-to-vigorous activity per week. Among patients with established cancer, physical activity equivalent to walking 1 or more hours per week was associated with improved survival compared with no exercise. The greatest benefit was observed among cancer survivors who performed exercise equivalent to 3–5 hours per week at an average pace. With respect to osteoporosis, the dose–response relation of physical activity is less clear. However, osteogenic adaptations appear to be load-dependent and site-specific. Accordingly, physical activities that require impact or significant loading are therefore advocated for optimal bone health. Running distances of up to 15–20 miles per week has been associated with the accrual or maintenance of bone mineral density, but longer distances may be associated with reduced bone mineral density (Mora, et.al, 2003).

 

8. How does Physical Activity and Fitness Lead to Improved Health Outcomes?

 

Several biological mechanisms may be responsible for the reduction in the risk of chronic disease and premature death associated with routine physical activity. For instance, routine physical activity has been shown to improve body composition (e.g., through reduced abdominal adiposity and improved weight control) enhance lipid lipoprotein profiles (e.g., through reduced triglyceride levels, increased high density lipoprotein [HDL] cholesterol levels and decreased low-density lipoprotein [LDL]-to-HDL ratios) (Warburton et.al, 2001), improve glucose homeostasis and insulin sensitivity, reduce blood pressure, improve autonomic tone, reduce systemic inflammation; decrease blood coagulation, improve coronary blood flow, augment cardiac function and enhance endothelial function. Chronic inflammation, as indicated by elevated circulating levels of inflammatory mediators such as C-reactive protein, has been shown to be strongly associated with most of the chronic diseases whose prevention has benefited from exercise. Recent studies have shown that exercise training may cause marked reductions in C-reactive protein levels. Each of these factors may explain directly or indirectly the reduced incidence of chronic disease and premature death among people who engage in routine physical activity. (Warburton et al, 2001).

 

Routine physical activity is also associated with improved psychological well-being (e.g., through reduced stress, anxiety and depression). Psychological well-being is particularly important for the prevention and management of cardiovascular disease, but it also has important implications for the prevention and management of other chronic diseases such as diabetes, osteoporosis, hypertension, obesity, cancer and depression.

 

Changes in endothelial function may be a particularly important adaptation to routine physical activity. Endothelial dysfunction has been observed with aging, smoking and multiple chronic disease states, including coronary artery disease, congestive heart failure, stroke, type 2 diabetes, hypertension, hypercholesterolemia and obesity. Regular aerobic activity has been found to improve vascular function in adults independent of changes in other risk factors and has been said to result in a shear-stress–mediated improvement in endothelial function, which confers a health benefit to a number of disease states.

 

Although most research into the mechanisms of how physical activity and fitness improve health outcomes has dealt with the relation between cardiovascular disease and physical activity, researchers have also evaluated the primary mechanisms responsible for decreases in the risk and severity of individual disease states. In fact, despite the adaptations that are of global benefit for multiple disease states, physical activity also results in specific adaptations that affect individual disease states. For instance, in type 2 diabetes, adaptations that affect glucose homeostasis are of great importance.

 

As reviewed by Ivy, (1997) a series of changes (independent of changes in body mass) occur as a result of regular physical activity, including increased glycogen synthase and hexokinase activity, increased GLUT-4 protein and mRNA expression, and improved muscle capillary density (resulting in improved glucose delivery to the muscle). A series of mechanisms may explain the 46% reduction in cancer rates observed with regular physical activity, including reductions in fat stores, increased energy expenditure offsetting a high fat diet, activity-related changes in sex hormone levels, immune function, insulin and insulin-like growth factors, free radical generation, and direct effects on the tumour. These acute changes indicate the important role individual exercise sessions have on health status.

 

9.Physical inactivity—a modifiable risk factor

 

Physical inactivity is the fourth leading cause of death worldwide (Kohl, et. al, 2012). It is estimated that over a third of cancers and about 80.0% of heart disease, stroke, and type 2 diabetes could be prevented by eliminating behavioral risk factors such as physical inactivity, unhealthy diet, tobacco smoking, and alcohol use. In a study designed to examine the population attributable risk of physical inactivity on death from diseases such as CHD, cancer, and diabetes, 6.0% to 10.0% of all deaths from non-communicable disease worldwide were attributed to physical inactivity. Specifically, in 5.6% of CHD, 7.0% of diabetes, 9.2% of breast cancer, 10.0% of colon cancer, and 9.1% of all-cause mortality were attributed to physical inactivity (Lee et al, 2012). These results suggest that 6.0% of the burden of non-communicable disease worldwide could be eliminated if all inactive people become active.

 

Furthermore, the public health burden of physical inactivity is similar in magnitude to that of obesity and even smoking. In 2008, it was estimated that physical inactivity contributed to 9.0% of premature mortality or more than 5.3 million of the 57.0 million deaths worldwide (Lee et.al, 2012). Health outcomes and conditions that are improved by physical activity and the proposed mechanisms they are improved by are shown in Table 1 and Table 2 (WHO, 2016).

 

10. Evidence for a role of specific genes

 

Up till now, only a few genes have been specifically associated with physical inactivity or physical activity traits in human studies focusing on this specific issue. These genes are the following: dopamine receptor D2 (DRD2), angiotensin converting enzyme (ACE), leptin receptor (LEPR),and melanocortin 4 receptor (MC4R).

  1. Summary
  •  Research indicates that the inclination to be physically active or sedentary has a biological foundation.
  • Twin and family studies confirm that physical activity-related traits are characterized by familial aggregation and influenced by genetic factors.
  • Results from animal model studies indicate that single genes can markedly influence physical activity-related behavior.
  • The first molecular genetic studies on physical activity traits in humans have been published during the last few years.
  • They support the notion that it is possible to detect relatively small, yet biologically important genetic effects impacting the tendency to be sedentary or physically active at the molecular level.
  • We are beginning to appreciate that the in utero environment and epigenetic events may play a role in postnatal physiology and behavior, but their impact on physical inactivity or physical activity level remains to be determined.
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GLOSSARY

 

Active daily living: The implementation of physical activity as an integral and meaningful part of daily living

 

Activities of daily living: The activities one engages in during daily life

 

Aerobic training: An exercise program that incorporates activities that are rhythmic in nature, using large muscle groups at moderate intensities for 3 to 5 days per week

 

Cardiovascular fitness: The ability to transport and use oxygen during prolonged, strenuous exercise or work. It reflects the combined efficiency of the lungs, heart, vascular system and exercising muscles in the transport and use of oxygen

 

Exercise: Structured and repetitive physical activity designed to maintain or improve physical fitness

 

Health-related physical fitness: The components of physical fitness that are related to health status, including cardiovascular fitness, musculoskeletal fitness, body composition and metabolism

 

Heart rate reserve: The difference between the maximum heart rate (predicted or determined directly) and the resting heart rate (HRmax — HRrest)

 

% heart rate reserve: This formula takes into account the resting and maximum heart rates to provide an appropriate target heart rate (or range) for training:

 

Training heart rate = ([HRmax — HRrest]  40%–85%) + HRrest

 

Maximum aerobic power: The maximum amount of oxygen that can be transported and used by the working muscles; also known as maximal oxygen consumption (VO2max)

 

Metabolic equivalent (MET): An estimate of one’s resting metabolic rate while sitting quietly (1 MET = 3.5 mL oxygen per kilogram per minute, or 1 kcal [4.2 kJ] per kilogram per hour)

 

Musculoskeletal fitness: The fitness of the musculoskeletal system, encompassing muscular strength, muscular endurance, muscular power, flexibility, back fitness and bone health

 

Physical activity: All leisure and non-leisure body movements resulting in an increased energy output from the resting condition

 

Physical fitness: A physiologic state of well-being that allows one to meet the demands of daily living or that provides the basis for sport performance, or both

 

Quality of life: An overall satisfaction and happiness with life. It includes the facets of physiologic, emotional, functional and spiritual well-being

 

Resistance training: An exercise program that uses repeated, progressive contractions of specific muscle groups to increase muscle strength, endurance or power

 

VO2 reserve: The difference between the maximum and resting oxygen consumption (VO2max — VO2rest)

 

% VO2 reserve: This formula takes into account the resting and maximum oxygen consumption to provide an appropriate level (or range) for training:

 

Training VO2 = ([VO2max —  40%–85%) + VO2rest

 

Interesting facts

  • Over 2,500 year ago, Hippocrates noted the potential health benefits of daily exercise of moderate intensity such as a simple walk.
  • Epidemiological studies have revealed that physical activity can reduce risks for preventing several chronic diseases and even reducing mortality
  • It is known that many different factors play a role in leisure-time physical activity behavior.
  • Genetic studies are one of the new areas of physical activity research.
  • Twin study designs are popular in behavioral genetics, as they provide an opportunity to disentangle the effects of genes from those of the environment
  • The recent findings on genetic and environmental influences on the longitudinal changes of leisure-time physical activity behavior as revealed in the twin studies
  • Physical activity has been defined to be body movements produced by the skeletal muscles, which cause a substantial increase in energy demands over resting energy expenditure
  • Physical inactivity is a major risk factor for complex metabolic diseases such as obesity, diabetes, and hypertension
  • In quantitative genetic modeling, physical activity is assumed to be made up of genetic and environmental contributions
  • Physical activity assessment methods may also have an influence on the heterogeneity of results.
  • In boys, genetic influences on leisure-time exercise behavior were fluctuating from age of 7 years to age of 12 years, while in girls genetic influences were more stable
  • Physical inactivity is a modifiable risk factor for cardiovascular disease and a widening variety of other chronic diseases, including diabetes mellitus, cancer (colon and breast), obesity, hypertension, bone and joint diseases
  • Physical fitness refers to a physiologic state of well-being that allows one to meet the demands of daily living or that provides the basis for sport performance, or both
  • It is apparent that physical activity is essential in the prevention of chronic disease and premature death.
  • Recently, investigators have postulated that even lower levels of weekly energy expenditure may be associated with health benefits.
  • Several biological mechanisms may be responsible for the reduction in the risk of chronic disease and premature death associated with routine physical activity.
  • Routine physical activity is also associated with improved psychological well-being.
  • Physical inactivity is the fourth leading cause of death worldwide
  • Up till now, only a few genes have been specifically associated with physical inactivity or physical activity traits in human studies focusing on this specific issue.

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