Forgotten Influences and Reflections on Exercise and on the End of the Year 2017
2017; Elsevier BV; Volume: 39; Issue: 12 Linguagem: Inglês
10.1016/j.clinthera.2017.11.003
ISSN1879-114X
Autores Tópico(s)Childhood Cancer Survivors' Quality of Life
ResumoThis Editor’s Creed and Sentiments for 2018Fulfillment is attained when one’s ideas, words, and deeds benefit others. An Exercise in Humor“Can you believe it? I just burned over 3000 calories!” “How,” you ask? “I made an apple pie and left it in the oven too long!” In my last Editor-in-Chief’s Note, I expressed concern about potential untoward consequences from the extensive use of smartphones and social media by youth.1Shader R.I. Musings on social media and GIST (gastrointestinal stromal cancer).Clin Ther. 2017; 39: 2122-2124Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar What I did not recall when I was crafting that piece was how much time I had spent in my own formative years listening on the radio to Lone Ranger, Roy Rogers, and other similar programs. I also did not remember my strong connection to them as a loyal and devoted fan. I belonged to the Roy Rogers Riders Club, and I sent away for the Lone Ranger Creed. In these same years, I was also a Cub Scout. Although I cannot know this with certainty, I suspect that these involvements played a significant role in my personal moral development. I wonder how many of today’s youth have had similar experiences from their social media and smartphone use. I am unaware of any current Marvel Comics or video game heroes who reach out to youth through inspiring codes, pledges, or creeds. One positive change is that American scouting is currently making efforts to be more diverse and inclusive. I searched the internet to find the oaths I pledged in those impressionable years. These are some of the elements that stand out for me: (1) from the Roy Rogers Riders Club Rules—“Protect the weak and help them” and “Study hard and learn all you can”2Roy Rogers Riders Club Rules. http://www.royrogers.com/happy_trails-index.html. Accessed November 6, 2017.Google Scholar; (2) from The Cub Scouts pledge— “To help other people at all times”3Boy Scout Oath, Law, Motto and Slogan and the Outdoor Code. http://www.usscouts.org/advance/boyscout/bsoathlaw.asp. Accessed November 6, 2017.Google Scholar; and (3) from the Lone Ranger Creed written in 1933— “That to have a friend, a man must be one” and “That all men are created equal and that everyone has within himself the power to make this a better world.”4The Lone Ranger Creed. http://loneranger.wikia.com/wiki/Lone_Ranger_Creed. Accessed November 6, 2017.Google Scholar At the time, I did not pick up on the male-biased language of these expectations. In addition, the Creed contained two ideas that I probably did not understand at the time. They now seem prescient and important— “That all things change but truth, and that truth alone, lives on forever” and “That sooner or later … somewhere … somehow … we must settle with the world and make payment for what we have taken.”4The Lone Ranger Creed. http://loneranger.wikia.com/wiki/Lone_Ranger_Creed. Accessed November 6, 2017.Google Scholar Through my search, I also came across additional wording added in early 2017 to the Australian Scout’s pledge: “To be true to my spiritual beliefs” and “To contribute to my community and our world.”5Scouts Australia. http://www.scouts.com.au. Accessed November 6, 2017.Google Scholar These alternative wordings were added to make scouting more acceptable to youth from a broader range of backgrounds. I applaud these efforts to increase the inclusiveness of scouting. On the other hand, I was appalled to read that an 11-year-old Cub was expelled from his den in Broomfield, Colorado because he asked a state senator why she was against common-sense gun laws, ones that would not allow domestic-violence offenders to have guns.6Hauser C. Cub scout is exiled after pressing legislator on guns and race. https://www.nytimes.com/2017/10/22/us/cub-scout-colorado.html?emc=eta. Accessed November 6, 2017.Google Scholar One of his direct questions was: “Why on earth would you want somebody who beats their wife to have access to a gun?” Even in the world of youth scouting, there should be room for and exposure to controversial views. My question is: Why was he expelled from his pack rather than using this as an opportunity for free and open discussion about a pressing and controversial topic? In addition to Roy Rogers, another Hollywood cowboy affected many youth—Gene Autry, also known as the Singing Cowboy. His real name was Orvon Grover Autry and many will remember him for two of his popular songs, “Back in the Saddle Again” and “Rudolph the Red-Nosed Reindeer.” Autry also coined the Cowboy Code.7Wikipedia. Gene Autry. https://en.wikipedia.org/wiki/Gene_Autry. Accessed November 6, 2017.Google Scholar These are some of its memorable ideas: “The Cowboy must never shoot first, hit a smaller man, or take unfair advantage”; “He must not advocate or possess racially or religiously intolerant ideas”; and “He must help people in distress.” These sentiments are particularly relevant today in many parts of the world. The Scout’s Oath and the Ranger’s Creed also stress the importance of physical fitness: “To keep myself physically strong, mentally awake, and morally straight” and to be “…prepared physically, mentally, and morally to fight when necessary for that which is right.” I had trouble with these physical expectations. I always preferred to read, build things, solve puzzles, or listen to my favorite programs. I admired my strong and powerful heroes, but I never thought I would become one; although for one Halloween I did wear a Superman cape. I was always a bit underweight until I went to college. In subsequent years, I gained weight—slowly and incrementally—now I struggle to keep my weight down. I learned during my early college years that I was not among those persons who enjoy and seek out exercise. An unknown author stated my views quite aptly: “I consider my refusal to go to the gym today as resistance training.”8The Quote Garden. Quotations about exercise. http://www.quotegarden.com/exercise.html. Accessed November 6, 2017.Google Scholar I particularly have to work at it during December, a month that is marked by overeating during the holiday season in many countries where food is readily available to the majority. Apple, blueberry, and pumpkin pies are irresistible. This is a truth I confess, knowing full well that there are millions who are starving in our unfair and imperfect world. In this unjust world, some of us have access to plenty, while others struggle to stay alive. Gene Tunney, a famous boxer, once said: “To enjoy the glow of good health, you must exercise.”9Inspiringquotes.us. Gene Tunney quotes and sayings. https://www.inspiringquotes.us/author/3465-gene-tunney. Accessed November 6, 2017.Google Scholar Both of my parents carried extra weight and neither had the time or inclination to exercise. My rationalization for my extra pounds and dislike of exercise is that my genes are the culprit; I do not mean the Genes, Autry and Tunney. Early in 2018, we will be publishing an Update on the merits of exercise for neurologic diseases. Prompted by reading some of these submissions, I decided to look into what is known about the genetics of exercise in order to explore why some people like to exercise while others do not, and why some even find it enjoyable while others find it abhorrent. As a user of 23andMe, I first turned to their website. I found nothing, so I contacted them. They replied that this is not a topic they have looked into thus far.10The 23 and Me Customer Care. Ticket #1243027: Exercise and genes. https://customercare.23andme.com/home?action=ask. Accessed November 6, 2017.Google Scholar Next, I looked for twin studies. When they exist, I have always found twin studies to be a good, preliminary way to assess hereditability. In a study of 37,051 twin pairs from seven different countries, Stubbs et al.11Stubbs J.H. Boomsma D.I. Vink J.M. et al.Genetic influences on exercise participation in 37,051 twin pairs from seven countries.PLoS One 1. 2006; : e22Crossref PubMed Scopus (208) Google Scholar examined the hereditability of voluntary exercise participation during leisure time using subjects from the GenomeEUtwin project. They used a well-defined criterion for exercise: 60 minutes or more per week in an activity with the intensity of four metabolic equivalents or more (one metabolic equivalent is equal to the energy expended sitting quietly in a chair). What was deemed to be exercise differed across countries. For example, gardening for an hour or more at least once weekly during leisure time met the equivalency requirements for Australians, while in Denmark light physical activity was contrasted with hard activity. In Norway, it was necessary to sweat during the activity to be called an exercise. Admittedly, this variability may make some question the value of their findings. Using a number of different mathematical approaches, they contrasted 13,676 monozygotic twin pairs with 23,375 dizygotic twin pairs. Stubbs and colleagues concluded that the median hereditability of exercise behavior across these seven countries was 62%. The range for men varied from 27% in Norway to 67% in Holland. For women, the range was from 48% in Australia to 71% in England. These authors did not genotype their study participants. In their discussion, they mention many possible contributors to voluntary exercise participation, including personality traits such as conscientiousness and self-discipline, mood alterations such as depression, monoamine depletion, genetically controlled heart rate recovery, and desire for weight loss. Some obvious additional factors are: body morphology, aerobic endurance, pain tolerance, and muscle strength and power. Another aspect to consider is that the genetics governing ability are not likely to be the sole determinants of performance. The latter is likely where motivation, perseverance, and training come into play. Having physically active parents also appears to be a determinant; offspring of active parents also tend to be active.12Moore L.L. Lombardi D.A. White M.J. et al.Influence of parents' physical activity levels on activity levels of young children.J Pediatr. 1991; 118: 215-219Abstract Full Text PDF PubMed Scopus (452) Google Scholar The report by Stubbs et al.11Stubbs J.H. Boomsma D.I. Vink J.M. et al.Genetic influences on exercise participation in 37,051 twin pairs from seven countries.PLoS One 1. 2006; : e22Crossref PubMed Scopus (208) Google Scholar contained 422 twin pairs from England who were part of the TwinsUK registry. Another group, den Hoed et al.,13den Hoed M. Brage S. Zhao J.H. et al.Heritability of objectively assessed daily physical activity and sedentary behavior.Am J Clin Nutr. 2013; 98: 1317-1325Crossref PubMed Scopus (73) Google Scholar studied 775 twin pairs from this same registry. I could not determine if there was any overlap in the two cohorts. The latter investigation concluded that 47% of the variance in physical activity energy expenditure and time spent in moderate to vigorous exercise was attributable to additive genetic factors. Some persons prefer to be sedentary during leisure time, while others involve themselves in self-chosen exercise behaviors. From these studies and others, it became apparent to me how complicated this whole area is. There are multiple dimensions involved, including but not limited to preferences, performance, adherence, and tolerability. Another paper I found particularly useful was by Ekkekakis et al.14Ekkekakis P. Hall E.E. Petruzzello S.J. Some like it vigorous: Measuring individual differences in the preference for and tolerance of exercise intensity.J Sport Exercise Psychol. 2005; 27: 350-374Crossref Scopus (136) Google Scholar The paper’s title includes the phrase “some like it vigorous.” They start by quoting a World Health Organization assessment that >60% of adults worldwide are not active enough to benefit their health. Their main goal was to develop a rating scale that could be used to assess preference for and tolerance of exercise intensity. The result was a 16-item, 2-factor scale. Preference means choosing a level of exercise intensity when involved in unsupervised exercise; tolerance refers to continuing at a given level or higher, even after it has begun to feel unpleasant or uncomfortable. Example items include: “I block out the feeling of fatigue when exercising” and “Low-intensity exercise is boring.” There are no questions assessing the preference to be sedentary. A twin study from Holland by van der Aa et al.15van der Aa N. De Geus E.J.C. van Beijsterveldt T.C.E.M. et al.Genetic Influences on Individual Differences in Exercise Behavior during Adolescence.Int J Pediatrics. 2010; 2010: 138345Crossref PubMed Google Scholar provides an additional perspective. They examined exercise behaviors in 8,355 Dutch twins (not all members of the twin pairs provided data) and concluded that genetic factors accounted for 72% to 85% of the variance in hereditability. This range was representative of all three age cohorts studied (13–14, 15–16, and 17–19 years) with one exception; shared environmental experiences accounted for 46% of the variance in 13- and 14-year-old girls. Sedentariness increased between early and late adolescence; overall, girls were more sedentary than boys. For those who preferred vigorous exercise, this pattern remained constant across age cohorts. The report’s authors speculate that exercise ability may be a contributing factor such that more sedentary adolescents are hindered by peer and societal emphasis on achievement and performance rather than on deriving pleasure from exercise. We all know that exercise increases muscle bulk and strength. Epigenetic changes also occur in exercised muscle. While a graduate student at the Karolinska Institutet in Stockholm, Malene Lindholm and her colleagues16Lindholm M.E. Marabita F. Gomez-Cabrero D. et al.An integrative analysis reveals coordinated reprogramming of the epigenome and the transcriptome in human skeletal muscle after training.Epigenetics. 2014; 9: 1557-1569Crossref PubMed Scopus (140) Google Scholar carried out an ingenious study to examine exercise-induced epigenetic changes in muscle. They recruited 23 volunteers to participate in a 3-month experiment that involved using only one leg to pedal a stationary bicycle four times a week for 45 minutes. Muscle biopsies and other tests were done before and after the 3-month intervention, and the non-exercised leg served as the control. This novel paradigm revealed, as a reflection of muscle adaptation to endurance training, that DNA methylation was altered significantly across the genome at close to 5000 sites, and about 4000 genes were differentially expressed. Interested readers may wish to examine their whole paper. This is a complicated and highly technical report; I was mainly informed through the Abstract and Discussion sections. Epigenetics is also involved in what many friends have called their “runners’ highs.” When I was coxswain for an 8-man shell during my first year in college, several rowers stated that they felt a “high” after a vigorous row. During the rowing season, I rowed in an indoor tank to keep my weight down; I never experienced any post-rowing elevations in mood. A number of studies conclude that exercise-induced increases in the levels of β-endorphin, brain-derived neurotrophic factor, and other endogenous euphoriants in brain underpin these highs.17Goldfarb A.H. Jamurtas A.Z. Beta-endorphin response to exercise. An update.Sports Med. 1997; 24: 8-16Crossref PubMed Scopus (180) Google Scholar, 18Dinas P.C. Koutedakis Y. Flouris A.D. Effects of exercise and physical activity on depression.Ir J Med Sci. 2011; 180: 319-325Crossref PubMed Scopus (213) Google Scholar, 19Szuhany K.L. Bugatti M. Otto M.W. A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor.J Psychiatr Res. 2014; 60C: 56-64Google Scholar Even sedentary individuals can have post-exercise mood elevations.20Heinonen I. Kalliokoski K.K. Hannukainen J.C. et al.Organ-specific physiological responses to acute physical exercise and long-term training in humans.Physiology. 2014; 29: 421-436Crossref PubMed Scopus (72) Google Scholar According to Civitarese et al.,21Civitarese A.E. Hesselink M.K.C. Russell A.P. et al.Glucose ingestion during exercise blunts exercise-induced gene expression of skeletal muscle fat oxidative genes.Am J Physiol Endocrinol Metab. 2005; 289: E1023-E1029Crossref PubMed Scopus (76) Google Scholar many gene transcripts increase after exercise; their abundance typically peaks within four hours and returns to basal levels within 24 hours. Because brain dopamine is considered to be important in reward circuitry and pleasurable feelings, I also looked into this area. In both rats and cats, regional concentrations of dopamine in brain have been found to increase during exercise.22Hattori S. Naoi M. Nishino H. Striatal dopamine turnover during treadmill running in the rat.Brain Res Bull. 1994; 35: 41-49Crossref PubMed Scopus (184) Google Scholar, 23Meeusen R. De Meirleir K. Exercise and brain neurotransmission.Sports Med. 1995; 20: 160-188Crossref PubMed Scopus (333) Google Scholar I could only locate one study in humans. In a positron emission tomography study in seven male and five female healthy volunteers, Wang et al.24Wang G.-J. Volkow N.D. Fowler J.S. et al.PET studies of the effects of aerobic exercise on human striatal dopamine release.J Nuclear Med. 2000; 41: 1352-1356PubMed Google Scholar found no significant increments in dopamine concentrations at brain synapses after 30 minutes of strenuous treadmill exercising. Although important to our overall understanding of genes and exercise, these molecular findings do not shed light on why some people are relatively sedentary, while others enjoy mild activities such as walking and casual bicycle riding, and still others push themselves to their limits of endurance. I next began a search for genotypes that predict exercise preference or athletic prowess. Most studies look at exercisers or athletes who have already chosen their preferred activity or sport and excel at it. I could not find any prospective or retrospective genotyping studies of youth who were followed to assess their preferences or performance abilities in their later years. I did find two cross-sectional studies that suggest that boys with ACTN3 RR polymorphisms may be faster swimmers and runners.25Chiu L.-L. Wu Y.-F. Tang M.-T. et al.ACTN3 genotype and swimming performance in Taiwan.Int J Sports Med. 2011; 32: 476-480Crossref PubMed Scopus (41) Google Scholar, 26Moran C.N. Yang N. Bailey M.E.S. et al.Association analysis of the ACTN3 R577X polymorphism and complex quantitative body composition and performance phenotypes in adolescent Greeks.Eur J Hum Genet. 2006; 15: 88-89Crossref PubMed Scopus (152) Google Scholar There are numerous studies in adults that show genetic differences on dimensions such as endurance and speed. These studies suggest that having particular genetic polymorphisms can make a difference in outcomes; however, they do not tell us when these genes emerged or whether these variants are inherited or acquired. I found two particular genes to be of interest: ACE, the gene for angiotensin converting enzyme, and ACTN3, a striatal muscle gene that encodes for α-actinin skeletal-muscle isoform 3 and is expressed specifically in fast type II muscle fibers.27Alvarez R. Terrados N. Ortolano R. et al.Genetic variation in the renin-angiotensin system and athletic performance.Eur J Appl Physiol. 2000; 82: 117-120Crossref PubMed Scopus (158) Google Scholar, 28Calvo M. Rodas G. Vallejo M. et al.Heritability of explosive power and anaerobic capacity in humans.Eur J Appl Physiol. 2002; 86: 218-225Crossref PubMed Scopus (55) Google Scholar, 29Gayagay G. Yu B. Hambly B. et al.Elite endurance athletes and the ACE I allele—the role of genes in athletic performance.Hum Genet. 1998; 103: 48-50Crossref PubMed Scopus (298) Google Scholar, 30Thompson J. Raitt J. Hutchings L. et al.Angiotensin-converting enzyme genotype and successful ascent to extreme high altitude.High Alt Med Biol. 2007; 8: 278-285Crossref PubMed Scopus (34) Google Scholar, 31Tsianos G. Eleftheriou K.I. Hawe E. et al.Performance at altitude and angiotensin I-converting enzyme genotype.Eur J Appl Physiol. 2005; 93: 630-633Crossref PubMed Scopus (43) Google Scholar, 32Thompson P.D. Tsongalis G.J. Ordovas J.M. et al.Angiotensin-converting enzyme genotype and adherence to aerobic exercise training.Prev Cardiol. 2006; 9: 21-24Crossref PubMed Scopus (18) Google Scholar, 33Montgomery H.E. Clarkson P. Dollery C.M. et al.Association of angiotensin-converting enzyme gene I/D polymorphism with change in left ventricular mass in response to physical training.Circulation. 1997; 96: 741-747Crossref PubMed Scopus (328) Google Scholar, 34Costa A.M. Silva A.J. Garrido N.D. et al.Association between ACE D allele and elite short distance swimming.Eur J Appl Physiol. 2009; 106: 785-790Crossref PubMed Scopus (54) Google Scholar, 35Eynon N. Alves A.J. Yamin C. et al.Is there an ACE ID—ACTN3 R577X polymorphisms interaction that influences sprint performance?.Int J Sports Med. 2009; 30: 888-891Crossref PubMed Scopus (31) Google Scholar, 36Amir O. Amir R. Chen Y. et al.The ACE deletion allele is associated with Israeli elite endurance athletes.Exp Physiol. 2007; 92: 881-886Crossref PubMed Scopus (100) Google Scholar ACE polymorphisms appear to be connected to aerobic fitness for endurance sports, and ACTN3 appears to be linked to muscular power and sprinting ability. Having the insertion/deletion (I/D) polymorphism of ACE leads to lower levels of the converting enzyme. This in turn is linked to better oxygen utilization during aerobic exercise. The I (insertion) refers to a polymorphism that includes the addition of a 287-base pair alanine sequence in intron 16. The D polymorphism lacks this sequence. Having the I/D polymorphism is good for marathon runners, distance bicyclers, and competitive rowers. Having the D allele also appears to be linked to muscle power, and it shows up more in successful short-distance swimmers. They have higher levels of angiotensin II, as a result of the actions of ACE on angiotensin. When I uncovered these associations, I wondered what would happen if these athletes were to take ACE inhibitors, such as lisinopril or enalapril. Would the “I/Ders” do even better? In those with the D alleles, would their associated increases in angiotensin II and its effects on bradykinin lead to more coughing and bronchospasms? To my surprise, both ACE inhibitors and angiotensin II receptor antagonists are acceptable treatments under the rules of the Medical Commission of the International Olympic Committee.37Fitch K. Proscribed drugs at the Olympic Games: permitted use and misuse (doping) by athletes.Clin Med. 2012; 12: 3257-3260Crossref Scopus (31) Google Scholar I was able to contact Professor Ken Fitch who authored the above cited reference. He kindly provided this information to explain why these agents are not banned: “In recent decades, the greatest endurance runners—both male and female—have been from Kenya and Ethiopia but detailed studies have revealed that elite runners from both of these countries do not have any association with ACE II or ACE ID gene polymorphism.” It seems likely that more genes will be studied extensively for their relationship to exercise preference and performance. Whether any gene or grouping of genes is necessary or essential for people to commit to regular exercise, adhere to it, or excel at it is still unknown. Because I could not locate any longitudinal or prospective studies that identify and follow specific genotypes, it is quite possible that the genes discussed above confer incremental or additive effects to other as yet unidentified genetic or non-genetic factor that may be involved. I know a number of families in which both parents are devoted to their hours at the gym but one (or more) of their children shows no inclination to engage in regular exercise. This Note marks the end of my first five years as Editor-in-Chief of Clinical Therapeutics. My Notes often contain information that reflects my personal ideas and experiences. Some may feel these are out of place in a scientific journal. I have even been asked why I have chosen to use this approach. Editing is both hard work and a gift. Each month I write on a new topic or bring new or additional perspectives to an old one. Writing a coherent and informative front piece takes time and considerable research; meeting monthly deadlines can be stressful. The gift is that it is stimulating to meet these challenges and rewarding to know that our growing international readership benefits from what we are able to publish, after careful and thorough peer review, from a wide variety of authors and countries. Scientific papers present new ideas and problem-solving strategies in a limited amount of space. By their very nature, they are devoid of humor and personal anecdotes. I bring them into my Notes in order to remind all of us to keep our focus on treating people rather than diseases and on the benefits of therapies (or their risks) rather than on molecules and pathways. In these trying times, we need to care for each other and for our planet. We need to learn and problem solve. We need to find better ways of coping, and, whenever possible, remind ourselves about the value of forgiveness and compromise.I wish you all a Happy New Year as we transition from 2017 to 2018. May we all contribute in whatever ways we can to improve the health and lives of others and bring about peaceful solutions to the vexing problems that face us all.
Referência(s)