﻿<?xml version="1.0" encoding="utf-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.1 20151215//EN" "JATS-journalpublishing1.dtd">
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="article-commentary">
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Explor Med</journal-id>
<journal-id journal-id-type="publisher-id">EM</journal-id>
<journal-title-group>
<journal-title>Exploration of Medicine</journal-title>
</journal-title-group>
<issn pub-type="epub">2692-3106</issn>
<publisher>
<publisher-name>Open Exploration Publishing</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.37349/emed.2023.00198</article-id>
<article-id pub-id-type="manuscript">1001198</article-id>
<article-categories>
<subj-group>
<subject>Commentary</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>From positive psychology to positive biology: laughter and longevity</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2427-6218</contrib-id>
<name>
<surname>Gonot-Schoupinsky</surname>
<given-names>Freda</given-names>
</name>
<role content-type="https://credit.niso.org/contributor-roles/conceptualization/">Conceptualization</role>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/">Writing—original draft</role>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/">Writing—review &amp; editing</role>
<xref ref-type="aff" rid="I1" />
<xref ref-type="corresp" rid="cor1">
<sup>*</sup>
</xref>
</contrib>
<contrib contrib-type="editor">
<name>
<surname>Caruso</surname>
<given-names>Calogero</given-names>
</name>
<role>Academic Editor</role>
<aff>University of Palermo, Italy</aff>
</contrib>
</contrib-group>
<aff id="I1">Department of Psychology, University of Bolton, BL3 5AB Bolton, UK</aff>
<author-notes>
<corresp id="cor1">
<bold>
<sup>*</sup>Correspondence:</bold> Freda Gonot-Schoupinsky, Department of Psychology, University of Bolton, BL3 5AB Bolton, UK. <email>fng1res@bolton.ac.uk</email></corresp>
</author-notes>
<pub-date pub-type="ppub">
<year>2023</year>
</pub-date>
<pub-date pub-type="epub">
<day>29</day>
<month>12</month>
<year>2023</year>
</pub-date>
<volume>4</volume>
<issue>6</issue>
<fpage>1109</fpage>
<lpage>1115</lpage>
<history>
<date date-type="received">
<day>05</day>
<month>08</month>
<year>2023</year>
</date>
<date date-type="accepted">
<day>19</day>
<month>10</month>
<year>2023</year>
</date>
</history>
<permissions>
<copyright-statement>© The Author(s) 2023.</copyright-statement>
<license xlink:href="https://creativecommons.org/licenses/by/4.0/">
<license-p>This is an Open Access article licensed under a Creative Commons Attribution 4.0 International License (<ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">https://creativecommons.org/licenses/by/4.0/</ext-link>), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.</license-p>
</license>
</permissions>
<abstract>
<p>Gelotology (the study of laughter) has it seems mainly evaded the attention of longevity scientists, positive biologists, and geroscientists. However, the potential of laughter to result in immediate improved affect, increase overall well-being, reduce cortisol levels, benefit the immune system, and support cardiovascular health, to name only a few of its possible effects, renders it of high interest as an anti-aging strategy. As an intervention, laughter has, at least theoretically, the potential to slow the process of aging, and to ameliorate its lived experience. What makes laughter particularly attractive is that it is accessible to all, is very low risk, and is inherently, for most people, enjoyable. Ten years ago, lifestyle medics first proposed that laughter be prescribed in primary care. They pointed to its efficacy in general patient care, geriatrics, rheumatology, critical care, oncology, rehabilitation, psychiatry, home care, palliative care, terminal care, and hospice care. Nevertheless, laughter prescription has been slow to take off. It is therefore of interest to contemplate why, how, and to what effect, laughter can be harnessed to improve people’s lives. Quality research is recommended to uncover the secrets of laughter, its dynamic effects on the body, if, and how, it may impact longevity, and how it can best be used to promote successful and active aging.</p>
</abstract>
<kwd-group>
<kwd>Longevity</kwd>
<kwd>laughter</kwd>
<kwd>laughter therapy</kwd>
<kwd>successful aging</kwd>
<kwd>centenarians</kwd>
<kwd>laughter prescription</kwd>
</kwd-group>
</article-meta>
</front>
<body>
<sec id="s1">
<title>Introduction</title>
<p id="p-1">Lifestyle and life experiences play an important role in longevity [<xref ref-type="bibr" rid="B1">1</xref>]. The link between subjective well-being (which covers positive affect, life satisfaction, and low negative affect) on health and all-cause mortality appears to be robust (e.g., [<xref ref-type="bibr" rid="B2">2</xref>–<xref ref-type="bibr" rid="B4">4</xref>]). As lifestyle and behaviours can be modified, a positive biology approach that investigates the phenotypes of the longevous is particularly pertinent [<xref ref-type="bibr" rid="B5">5</xref>]. Positive biology includes insight into how to improve well-being including by increasing opportunities for play and joy [<xref ref-type="bibr" rid="B6">6</xref>]. This is relevant as a meta-analysis of 150 studies [<xref ref-type="bibr" rid="B7">7</xref>] indicated that “the probability of living longer increases by 14% for individuals with high well-being compared to those with low well-being”. A range of behaviours are associated with well-being, happiness, and positive affect, but one that is accessible to all is laughter. Calls from the medical community highlighting the prescriptive potential of laughter [<xref ref-type="bibr" rid="B8">8</xref>], motivated the conception of the one-minute Laughie (Laugh Intentionally Everyday) laughter prescription [<xref ref-type="bibr" rid="B9">9</xref>], and PhD research on the psychology of laughter prescription [<xref ref-type="bibr" rid="B10">10</xref>]. The purpose of this commentary is to briefly investigate evidence from positive psychology to positive biology that may support the hypothesis that laughter can promote longevity, and reduce, prevent, or delay diseases associated with aging.</p>
<p id="p-2">Positive psychology focuses on how to live happy and meaningful lives including by developing inherent “character strengths”, one of which (of the 24 strengths identified) is humour [<xref ref-type="bibr" rid="B11">11</xref>]. Positive biology, on the other hand, seeks to investigate positive phenotypes associated with longevity [<xref ref-type="bibr" rid="B6">6</xref>]. Both positive psychology and positive biology are concerned with physiology and applied research. William Fry, the “father of gelotology”, saw laughter as an especially profitable overall body exercise for the elderly to counteract aging due to its cardiovascular benefits and potential to stimulate circulation, and strengthen and relax muscles [<xref ref-type="bibr" rid="B12">12</xref>]. Laughter is a particularly suitable behaviour to improve well-being in seniors by inducing positive affect and mitigating negative affect as it is a low-impact exercise, is accessible to all, is low risk, and it can have an immediate effect. Moreover, it can be undertaken intentionally, and without excess: Just one minute of intentional laughter, alone, or with others, has been found to improve well-being [<xref ref-type="bibr" rid="B9">9</xref>, <xref ref-type="bibr" rid="B13">13</xref>]. To date, few centenarian studies have directly investigated laughter. In the Longevity Genes Project of independently living Ashkenazi Jewish centenarians (<italic>n</italic> = 243; age 95–107), Kato et al. [<xref ref-type="bibr" rid="B14">14</xref>] identified a positive attitude towards life as a centenarian personality phenotype. They also found that these centenarians tended “to consider laughter as an important part of their life”.</p>
</sec>
<sec id="s2">
<title>Evidence that may support a laughter-longevity link</title>
<p id="p-3">Anecdotal evidence associating laughter with longevity is rich and dates back 4,000 years to Democritus, named the “laughing philosopher” for his penchant to laugh, often alone, at the absurdity of life. So concerned were his fellow Abderians, that they invited Hippocrates to provide a diagnosis [<xref ref-type="bibr" rid="B15">15</xref>]. Hippocrates found nothing amiss. Democritus, a “father of science”, supposedly died aged 109 [<xref ref-type="bibr" rid="B16">16</xref>]. The oldest seemingly verified person to ever live was the super-centenarian Frenchwoman Jeanne Calment. She died in 1997 aged 122. According to her biographers [<xref ref-type="bibr" rid="B17">17</xref>], Calment advised “Always keep your sense of humor. That’s what I attribute my long life to. I think I’ll die laughing. That’s part of my program.”</p>
<p id="p-4">One Korean study on successful aging [<xref ref-type="bibr" rid="B18">18</xref>], compared laughter frequency in centenarians (<italic>n</italic> = 109), octogenarians (<italic>n</italic> = 135), and sexagenarians (<italic>n</italic> = 145). Centenarians scored higher in “laughing more than two times a day” than the sexagenarians and the octogenarians. In Japan, research comparing laughter frequency to health outcomes, particularly using the Japan Gerontological Evaluation Study (JAGES, adults aged 65 years and over) cohort, is well-developed. For example, Hayashi et al. [<xref ref-type="bibr" rid="B19">19</xref>] reported that daily laughter can support subjective health in older adults (<italic>n</italic> = 26,368). Hayashi et al. [<xref ref-type="bibr" rid="B20">20</xref>], found daily laughter was associated with lower cardiovascular disease prevalence (<italic>n</italic> = 20,934). And Tamada et al. [<xref ref-type="bibr" rid="B21">21</xref>], found that the risk of functional disability was 1.42 times higher in those who did not laugh most days (<italic>n</italic> = 14,233). Meanwhile, Hirosaki et al. [<xref ref-type="bibr" rid="B22">22</xref>], found a significant association between laughter frequency and oral health (<italic>n</italic> = 24,038). And Wang et al. [<xref ref-type="bibr" rid="B23">23</xref>], found laughing with friends, children, grandchildren, or the radio was associated with a decreased risk for dementia (<italic>n</italic> = 12,165). Another Japanese prospective cohort study [<xref ref-type="bibr" rid="B24">24</xref>], in those aged 40 years and over [<italic>n</italic> = 17,152; mean (M) = 62.8], also found low laughter frequency was independently associated with cardiovascular disease and, moreover, all-cause mortality. Research is ongoing and a recent study [<xref ref-type="bibr" rid="B25">25</xref>] points to a protective effect of laughter frequency on hypertension in older Japanese adults (<italic>n</italic> = 22,503).</p>
<p id="p-5">The majority of the studies mentioned so far rely on cross-sectional data interpretation. Nevertheless, the epigenetic impact of laughter and humour on phenotype has been investigated, and seemingly demonstrated. For example, Hayashi et al. [<xref ref-type="bibr" rid="B26">26</xref>] found that 23 out of 18,716 genes in older patients (<italic>n</italic> = 12; M = 63) with type 2 diabetes had significant gene expression changes following a laughing episode. In a subsequent study [<xref ref-type="bibr" rid="B27">27</xref>], the authors discovered that many of those genes were implicated in improved natural killer cell activity.</p>
<p id="p-6">A systematic review of seven laughter yoga studies [<xref ref-type="bibr" rid="B28">28</xref>] in older adults (65 years and over) found laughter yoga was effective in improving physical function and psychosocial outcomes. Ko and Youn [<xref ref-type="bibr" rid="B29">29</xref>] found a beneficial effect of laughter therapy on cognition, sleep, and depression, in a randomized control trial (RCT) in Korean community-dwelling elderly (<italic>n</italic> = 109; M = 76). Recent RCTs have also highlighted benefits for older adults. Significant changes in body mass index (BMI), cognitive function, functional activity, blood pressure, and depression in the “elderly” in Egypt (<italic>n</italic> = 60; M = 66) were revealed following three laughter yoga sessions [<xref ref-type="bibr" rid="B30">30</xref>], and significant amelioration in depression and anxiety following 16 sessions (<italic>n</italic> = 62, retired women) in Iran [<xref ref-type="bibr" rid="B31">31</xref>].</p>
<p id="p-7">Laughter therapy, in various forms (e.g., laughter yoga, humour therapy, clown therapy, laughter qigong, and the Laughie laughter prescription) can be beneficial for a range of conditions that impact older adults from low levels of well-being through to cancer, cardiovascular disease, and diabetes. For example, a seven-week laughter therapy RCT [<xref ref-type="bibr" rid="B32">32</xref>] reported significant reductions in pain in cancer patients (<italic>n</italic> = 61; M = 55). Another Japanese study [<xref ref-type="bibr" rid="B33">33</xref>], 12-week RCT for those at risk from metabolic syndrome (<italic>n</italic> = 235; M = 67), reported significant benefits to body weight, well-being, and optimism. Laughter has also been found to regulate homeostatic abnormalities associated with type 2 diabetes [<xref ref-type="bibr" rid="B34">34</xref>].</p>
<p id="p-8">As shown, laughter appears to have wide-ranging positive impact on physiology and psychology. In order to research and harness these benefits daily, the Laughie laughter prescription has been proposed, including for the promotion of healthy and successful aging in the oldest-old [<xref ref-type="bibr" rid="B35">35</xref>]. Two recent theoretical models speculate on how habitual and intentional laughter may ameliorate psychophysiology and neuroimmunology (i.e. the “positive biology” Laugh-Health model), as well as emotion and affect (i.e. the “positive psychology” Laugh-Thrive model) [<xref ref-type="bibr" rid="B10">10</xref>]. The pertinence of the evidence underpinning these models to the potential physiological determinants of laughter on longevity will now be contemplated.</p>
</sec>
<sec id="s3">
<title>What are the physiological mechanisms involved?</title>
<p id="p-9">As a physical behaviour, laughter can provide exercise that involves abdominal muscles, facial muscles, and lungs. This may explain why many of the physiological benefits of laughter are those that can be seen in physical exercise. Fry [<xref ref-type="bibr" rid="B12">12</xref>] found laughter impacted most if not all physiologic systems, and stated that while we cannot laugh away our natural aging process, laughter can modify its impact. Fry [<xref ref-type="bibr" rid="B12">12</xref>] viewed laughter as an advantageous all-body and cardio-vascular exercise that is particularly beneficial for the elderly for whom traditional and strenuous exercise may not be feasible. Research has supported this vision of laughter as exercise. One small study even found laughter, albeit in the form of laughter yoga, to be superior to “traditional exercise” for trunk muscle function following assessment of its impact on abdominal, paraspinal, and internal oblique muscles [<xref ref-type="bibr" rid="B36">36</xref>]. As with any exercise, laughter also needs to be undertaken regularly to harness ongoing benefits, hence the pertinence of laughter prescription.</p>
<p id="p-10">The potential far-reaching and dynamic impact of laughter on physiology, psychophysiology, and neuroimmunology can be linked to the release of chemicals including “feel-good” endorphins during laughter [<xref ref-type="bibr" rid="B37">37</xref>]. Laughter has been associated with ameliorating serotonin levels and the dopaminergic reward system. For example, in a study (<italic>n</italic> = 10) undertaken by Berk et al. [<xref ref-type="bibr" rid="B38">38</xref>], 3,4,-dihy-drophenylacetic acid (DOPAC), a dopamine catabolite, appeared to be regulated by mirthful (i.e. humour-induced) laughter. A range of studies have found that laughter can decrease cortisol [<xref ref-type="bibr" rid="B38">38</xref>, <xref ref-type="bibr" rid="B39">39</xref>], a primary stress hormone, as well as epinephrine/adrenalin [<xref ref-type="bibr" rid="B38">38</xref>]. Miller and Fry [<xref ref-type="bibr" rid="B37">37</xref>] hypothesized that laughter results in the release of nitric oxide (NO), potentially providing a mechanism linking positive emotions to vascular health. This could be one explanation for the benefits of laughter on endothelial function [<xref ref-type="bibr" rid="B37">37</xref>] implicated in arthrosclerosis, diabetes, coronary artery disease, and hypertension. Nevertheless, while aging has been associated with reduced NO bioavailability, this mechanism is not fully elucidated (e.g., [<xref ref-type="bibr" rid="B40">40</xref>]).</p>
<p id="p-11">In addition to the benefits of laughter on overall and cardiovascular health (e.g., [<xref ref-type="bibr" rid="B37">37</xref>]), there is evidence that laughter can ameliorate a range of biomarkers associated with aging, including cytokines, blood pressure, and inflammation (“inflamm-aging” [<xref ref-type="bibr" rid="B41">41</xref>]). For example, mirthful laughter was found to attenuate inflammatory cytokines implicated in diabetes and benefitted metabolic function by raising “good” high-density lipoprotein (HDL) cholesterol in a study (<italic>n</italic> = 20) by Berk and Tan [<xref ref-type="bibr" rid="B42">42</xref>]. Both heart rate and levels of C-reactive protein (CRP), an inflammatory biomarker, were found to reduce in a study by Bains et al. [<xref ref-type="bibr" rid="B43">43</xref>] following laughter induced by a humorous video (<italic>n</italic> = 32).</p>
</sec>
<sec id="s4">
<title>Caveats to consider</title>
<p id="p-12">While there is a growing body of evidence for the benefits of laughter on health, and thus by implication on longevity, larger scale studies are needed in order to investigate and clarify cause-effect pathways. More precision is also needed in measuring laughter and elucidating its benefits before we can be assured of the effects of laughter <italic>per se</italic> in interventions [<xref ref-type="bibr" rid="B44">44</xref>]. This is because laughter therapy can involve a number of confounding variables, including non-laughter driven physical exercises, humour, and social interactions. Furthermore, while many large-scale studies support the plausibility of a laughter-longevity link, most rely on one self-report laughter item only (e.g., “How often do you laugh out loud?”, [<xref ref-type="bibr" rid="B24">24</xref>]), which is overly simplistic. Precise laughter measurements, and for prescription purposes minimum effective dose insight, are needed [<xref ref-type="bibr" rid="B10">10</xref>].</p>
<p id="p-13">Laughter is also associated with pathology, and little is known about the mechanisms involved. For example, dysfunctional serotonin and glutamine neurotransmission are implicated in pseudobulbar affect [<xref ref-type="bibr" rid="B45">45</xref>]. While laughter is very low risk [<xref ref-type="bibr" rid="B46">46</xref>], death by laughter has been recorded. Most well-known cases are anecdotal and distant. For example, the Stoic Chrysippus is said to have died laughing at his own joke (he enquired of a donkey if it would also enjoy some wine, on seeing the donkey eat figs from his silver platter). Another point to consider is that some study results can be interpreted as running contrary to a potential laughter-longevity link. For example, Rotton [<xref ref-type="bibr" rid="B47">47</xref>] compared the biographical details of over 1,000 comedians, entertainers, and writers, and found no association between the ability to generate humour and longevity. However, Rotton [<xref ref-type="bibr" rid="B47">47</xref>] did not investigate laughter.</p>
<p id="p-14">Laughter and humour are often confounded, but they are distinct [<xref ref-type="bibr" rid="B48">48</xref>]. Intentional laughter as an exercise, with or without humour, is not intuitive for many people, nor is laughing alone, but it can be learnt. Solirisy, a term for laughing alone, may have a place as a prescribed exercise [<xref ref-type="bibr" rid="B10">10</xref>]. Laughter interventions can be tailored to preferences. Gelotophobia, or the fear of laughter, is thought to affect up to 20% of the population [<xref ref-type="bibr" rid="B49">49</xref>]; however, laughter interventions may be used to address this issue.</p>
</sec>
<sec id="s5">
<title>Concluding thoughts</title>
<p id="p-15">A positive biology approach that explores the role of lifestyle, life experiences, and behavioural patterns on aging is recommended to advance insight into longevity [<xref ref-type="bibr" rid="B1">1</xref>, <xref ref-type="bibr" rid="B50">50</xref>]. To date, a range of interventions to slow aging in humans have been proposed (e.g., [<xref ref-type="bibr" rid="B51">51</xref>]). However, thus far, laughter does not feature on most lists. What makes laughter particularly attractive to investigate is its accessibility, immediate impact, low risk, unique social bonding qualities rendering it ideal to be undertaken with others, and its capacity to also be enjoyed alone. Evidence for a clear laughter-longevity link is tenuous, in part perhaps because it has not been an area of interest for longevity scientists. Nevertheless, an increasing body of research is providing evidence that laughter can ameliorate a range of age-related conditions, and lending weight to recommendations that laughter be endorsed to support successful aging. Positive psychology and positive biology investigation of the psychophysiological impact of laughter on aging and longevity merit more attention.</p>
</sec>
</body>
<back>
<glossary>
<title>Abbreviations</title>
<def-list>
<def-item>
<term>M</term>
<def>
<p>mean</p>
</def>
</def-item>
<def-item>
<term>RCT</term>
<def>
<p>randomized control trial</p>
</def>
</def-item>
</def-list>
</glossary>
<sec id="s6">
<title>Declarations</title>
<sec>
<title>Author contributions</title>
<p>FGS: Conceptualization, Writing—original draft, Writing—review &amp; editing.</p>
</sec>
<sec sec-type="COI-statement">
<title>Conflicts of interest</title>
<p>The author declares that she has no conflicts of interest.</p>
</sec>
<sec>
<title>Ethical approval</title>
<p>Not applicable.</p>
</sec>
<sec>
<title>Consent to participate</title>
<p>Not applicable.</p>
</sec>
<sec>
<title>Consent to publication</title>
<p>Not applicable.</p>
</sec>
<sec sec-type="data-availability">
<title>Availability of data and materials</title>
<p>Not applicable.</p>
</sec>
<sec>
<title>Funding</title>
<p>Not applicable.</p>
</sec>
<sec>
<title>Copyright</title>
<p>© The Author(s) 2023.</p>
</sec>
</sec>
<ref-list>
<ref id="B1">
<label>1</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Caruso</surname>
<given-names>C</given-names>
</name>
<name>
<surname>Ligotti</surname>
<given-names>ME</given-names>
</name>
<name>
<surname>Accardi</surname>
<given-names>G</given-names>
</name>
<name>
<surname>Aiello</surname>
<given-names>A</given-names>
</name>
<name>
<surname>Duro</surname>
<given-names>G</given-names>
</name>
<name>
<surname>Galimberti</surname>
<given-names>D</given-names>
</name>
<etal>et al.</etal>
</person-group>
<article-title>How important are genes to achieve longevity?</article-title>
<source>Int J Mol Sci</source>
<year iso-8601-date="2022">2022</year>
<volume>23</volume>
<elocation-id>5635</elocation-id>
<pub-id pub-id-type="doi">10.3390/ijms23105635</pub-id><pub-id pub-id-type="pmid">35628444</pub-id><pub-id pub-id-type="pmcid">PMC9145989</pub-id></element-citation>
</ref>
<ref id="B2">
<label>2</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Diener</surname>
<given-names>E</given-names>
</name>
<name>
<surname>Chan</surname>
<given-names>MY</given-names>
</name>
</person-group>
<article-title>Happy people live longer: subjective well‐being contributes to health and longevity</article-title>
<source>Appl Psychol Health Well-Being</source>
<year iso-8601-date="2011">2011</year>
<volume>3</volume>
<fpage>1</fpage>
<lpage>43</lpage>
<pub-id pub-id-type="doi">10.1111/j.1758-0854.2010.01045.x</pub-id></element-citation>
</ref>
<ref id="B3">
<label>3</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Chei</surname>
<given-names>CL</given-names>
</name>
<name>
<surname>Lee</surname>
<given-names>JM</given-names>
</name>
<name>
<surname>Ma</surname>
<given-names>S</given-names>
</name>
<name>
<surname>Malhotra</surname>
<given-names>R</given-names>
</name>
</person-group>
<article-title>Happy older people live longer</article-title>
<source>Age Ageing</source>
<year iso-8601-date="2018">2018</year>
<volume>47</volume>
<fpage>860</fpage>
<lpage>6</lpage>
<pub-id pub-id-type="doi">10.1093/ageing/afy128</pub-id><pub-id pub-id-type="pmid">30165421</pub-id></element-citation>
</ref>
<ref id="B4">
<label>4</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Beller</surname>
<given-names>J</given-names>
</name>
</person-group>
<article-title>Loneliness and mortality: the moderating effect of positive affect</article-title>
<source>Appl Psychol Health Well Being</source>
<year iso-8601-date="2023">2023</year>
<volume>15</volume>
<fpage>49</fpage>
<lpage>65</lpage>
<pub-id pub-id-type="doi">10.1111/aphw.12354</pub-id><pub-id pub-id-type="pmid">35233957</pub-id></element-citation>
</ref>
<ref id="B5">
<label>5</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Caruso</surname>
<given-names>C</given-names>
</name>
<name>
<surname>Passarino</surname>
<given-names>G</given-names>
</name>
<name>
<surname>Puca</surname>
<given-names>A</given-names>
</name>
<name>
<surname>Scapagnini</surname>
<given-names>G</given-names>
</name>
</person-group>
<article-title>“Positive biology”: the centenarian lesson</article-title>
<source>Immun Ageing</source>
<year iso-8601-date="2012">2012</year>
<volume>9</volume>
<elocation-id>5</elocation-id>
<pub-id pub-id-type="doi">10.1186/1742-4933-9-5</pub-id><pub-id pub-id-type="pmid">22524297</pub-id><pub-id pub-id-type="pmcid">PMC3412734</pub-id></element-citation>
</ref>
<ref id="B6">
<label>6</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Farrelly</surname>
<given-names>C</given-names>
</name>
</person-group>
<article-title>‘Positive biology’ as a new paradigm for the medical sciences. Focusing on people who live long, happy, healthy lives might hold the key to improving human well-being</article-title>
<source>EMBO Rep</source>
<year iso-8601-date="2012">2012</year>
<volume>13</volume>
<fpage>186</fpage>
<lpage>8</lpage>
<pub-id pub-id-type="doi">10.1038/embor.2011.256</pub-id><pub-id pub-id-type="pmid">22281805</pub-id><pub-id pub-id-type="pmcid">PMC3323127</pub-id></element-citation>
</ref>
<ref id="B7">
<label>7</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Howell</surname>
<given-names>RT</given-names>
</name>
<name>
<surname>Kern</surname>
<given-names>ML</given-names>
</name>
<name>
<surname>Lyubomirsky</surname>
<given-names>S</given-names>
</name>
</person-group>
<article-title>Health benefits: meta-analytically determining the impact of well-being on objective health outcomes</article-title>
<source>Health Psychol Rev</source>
<year iso-8601-date="2007">2007</year>
<volume>1</volume>
<fpage>83</fpage>
<lpage>136</lpage>
<pub-id pub-id-type="doi">10.1080/17437190701492486</pub-id></element-citation>
</ref>
<ref id="B8">
<label>8</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Louie</surname>
<given-names>D</given-names>
</name>
<name>
<surname>Brook</surname>
<given-names>K</given-names>
</name>
<name>
<surname>Frates</surname>
<given-names>E</given-names>
</name>
</person-group>
<article-title>The laughter prescription: a tool for lifestyle medicine</article-title>
<source>Am J Lifestyle Med</source>
<year iso-8601-date="2016">2016</year>
<volume>10</volume>
<fpage>262</fpage>
<lpage>7</lpage>
<pub-id pub-id-type="doi">10.1177/1559827614550279</pub-id><pub-id pub-id-type="pmid">30202281</pub-id><pub-id pub-id-type="pmcid">PMC6125057</pub-id></element-citation>
</ref>
<ref id="B9">
<label>9</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Gonot-Schoupinsky</surname>
<given-names>FN</given-names>
</name>
<name>
<surname>Garip</surname>
<given-names>G</given-names>
</name>
</person-group>
<article-title>Prescribing laughter to increase well-being in healthy adults: an exploratory mixed methods feasibility study of the Laughie</article-title>
<source>Eur J Integr Med</source>
<year iso-8601-date="2019">2019</year>
<volume>26</volume>
<fpage>56</fpage>
<lpage>64</lpage>
<pub-id pub-id-type="doi">10.1016/J.EUJIM.2019.01.005</pub-id></element-citation>
</ref>
<ref id="B10">
<label>10</label>
<element-citation publication-type="thesis">
<person-group person-group-type="author">
<name>
<surname>Gonot-Schoupinsky</surname>
<given-names>F</given-names>
</name>
</person-group>
<comment>Critical commentary. The psychology of laughter prescription: contributions to the research literature on laughter and humour [unpublished dissertation]. Bolton: University of Bolton.</comment>
</element-citation>
</ref>
<ref id="B11">
<label>11</label>
<element-citation publication-type="book">
<person-group person-group-type="author">
<name>
<surname>Macfarlane</surname>
<given-names>J</given-names>
</name>
<name>
<surname>Carson</surname>
<given-names>J</given-names>
</name>
</person-group>
<article-title>Humour</article-title>
<comment>In: Positive psychology for healthcare professionals: a toolkit for improving wellbeing (positive psychology in practice). Leeds: Emerald Publishing Limited; 2023. pp. 71–7.</comment>
</element-citation>
</ref>
<ref id="B12">
<label>12</label>
<element-citation publication-type="book">
<person-group person-group-type="author">
<name>
<surname>Fry</surname>
<given-names>WF</given-names>
</name>
</person-group>
<article-title>Humor, physiology, and the aging process</article-title>
<person-group person-group-type="editor">
<name>
<surname>Nahemow</surname>
<given-names>L</given-names>
</name>
<name>
<surname>McCluskey-Fawcett</surname>
<given-names>KA</given-names>
</name>
<name>
<surname>McGhee</surname>
<given-names>PE</given-names>
</name>
</person-group>
<source>Humor and aging</source>
<comment>Academic Press; 1986. pp. 81–98.</comment>
</element-citation>
</ref>
<ref id="B13">
<label>13</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Foley</surname>
<given-names>E</given-names>
</name>
<name>
<surname>Matheis</surname>
<given-names>R</given-names>
</name>
<name>
<surname>Schaefer</surname>
<given-names>C</given-names>
</name>
</person-group>
<article-title>Effect of forced laughter on mood</article-title>
<source>Psychol Rep</source>
<year iso-8601-date="2002">2002</year>
<volume>90</volume>
<elocation-id>184</elocation-id>
<pub-id pub-id-type="doi">10.2466/pr0.2002.90.1.184</pub-id><pub-id pub-id-type="pmid">11898980</pub-id></element-citation>
</ref>
<ref id="B14">
<label>14</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Kato</surname>
<given-names>K</given-names>
</name>
<name>
<surname>Zweig</surname>
<given-names>R</given-names>
</name>
<name>
<surname>Barzilai</surname>
<given-names>N</given-names>
</name>
<name>
<surname>Atzmon</surname>
<given-names>G</given-names>
</name>
</person-group>
<article-title>Positive attitude towards life and emotional expression as personality phenotypes for centenarians</article-title>
<source>Aging (Albany NY)</source>
<year iso-8601-date="2012">2012</year>
<volume>4</volume>
<fpage>359</fpage>
<lpage>67</lpage>
<pub-id pub-id-type="doi">10.18632/aging.100456</pub-id><pub-id pub-id-type="pmid">22626632</pub-id><pub-id pub-id-type="pmcid">PMC3384436</pub-id></element-citation>
</ref>
<ref id="B15">
<label>15</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Temkin</surname>
<given-names>O</given-names>
</name>
</person-group>
<article-title>Hippocrates as the physician of Democritus</article-title>
<source>Gesnerus</source>
<year iso-8601-date="1985">1985</year>
<volume>42</volume>
<fpage>455</fpage>
<lpage>64</lpage>
<pub-id pub-id-type="pmid">3912280</pub-id></element-citation>
</ref>
<ref id="B16">
<label>16</label>
<element-citation publication-type="book">
<person-group person-group-type="author">
<name>
<surname>Withington</surname>
<given-names>J</given-names>
</name>
</person-group>
<source>Secrets of the centenarians: What is it like to live for a century and which of us will survive to find out? London: Reaktion Books; 2017</source>
</element-citation>
</ref>
<ref id="B17">
<label>17</label>
<element-citation publication-type="book">
<person-group person-group-type="author">
<name>
<surname>Jeune</surname>
<given-names>B</given-names>
</name>
<name>
<surname>Robine</surname>
<given-names>JM</given-names>
</name>
<name>
<surname>Young</surname>
<given-names>R</given-names>
</name>
<name>
<surname>Desjardins</surname>
<given-names>B</given-names>
</name>
<name>
<surname>Skytthe</surname>
<given-names>A</given-names>
</name>
<name>
<surname>Vaupel</surname>
<given-names>JW</given-names>
</name>
</person-group>
<article-title>Jeanne Calment and her successors. Biographical notes on the longest living humans</article-title>
<person-group person-group-type="editor">
<name>
<surname>Maier</surname>
<given-names>H</given-names>
</name>
<name>
<surname>Gampe</surname>
<given-names>J</given-names>
</name>
<name>
<surname>Jeune</surname>
<given-names>B</given-names>
</name>
<name>
<surname>Robine</surname>
<given-names>JM</given-names>
</name>
<name>
<surname>Vaupel</surname>
<given-names>J</given-names>
</name>
</person-group>
<source>Supercentenarians</source>
<publisher-loc>Berlin</publisher-loc>
<publisher-name>Springer</publisher-name>
<year iso-8601-date="2010">2010</year>
<comment>pp. 285–323.</comment>
</element-citation>
</ref>
<ref id="B18">
<label>18</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Kim</surname>
<given-names>JI</given-names>
</name>
</person-group>
<article-title>Differences in longevity factors amongst Korean centenarians, octogenarians, and sexagenarians</article-title>
<source>Korean J Health Educ Promot</source>
<year iso-8601-date="2007">2007</year>
<volume>24</volume>
<fpage>55</fpage>
<lpage>68</lpage>
</element-citation>
</ref>
<ref id="B19">
<label>19</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Hayashi</surname>
<given-names>K</given-names>
</name>
<name>
<surname>Kawachi</surname>
<given-names>I</given-names>
</name>
<name>
<surname>Ohira</surname>
<given-names>T</given-names>
</name>
<name>
<surname>Kondo</surname>
<given-names>K</given-names>
</name>
<name>
<surname>Shirai</surname>
<given-names>K</given-names>
</name>
<name>
<surname>Kondo</surname>
<given-names>N</given-names>
</name>
</person-group>
<article-title>Laughter and subjective health among community-dwelling older people in Japan: cross-sectional analysis of the Japan gerontological evaluation study cohort data</article-title>
<source>J Nerv Ment Dis</source>
<year iso-8601-date="2015">2015</year>
<volume>203</volume>
<fpage>934</fpage>
<lpage>42</lpage>
<pub-id pub-id-type="doi">10.1097/NMD.0000000000000399</pub-id><pub-id pub-id-type="pmid">26649930</pub-id><pub-id pub-id-type="pmcid">PMC4892770</pub-id></element-citation>
</ref>
<ref id="B20">
<label>20</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Hayashi</surname>
<given-names>K</given-names>
</name>
<name>
<surname>Kawachi</surname>
<given-names>I</given-names>
</name>
<name>
<surname>Ohira</surname>
<given-names>T</given-names>
</name>
<name>
<surname>Kondo</surname>
<given-names>K</given-names>
</name>
<name>
<surname>Shirai</surname>
<given-names>K</given-names>
</name>
<name>
<surname>Kondo</surname>
<given-names>N</given-names>
</name>
</person-group>
<article-title>Laughter is the best medicine? A cross-sectional study of cardiovascular disease among older Japanese adults</article-title>
<source>J Epidemiol</source>
<year iso-8601-date="2016">2016</year>
<volume>26</volume>
<fpage>546</fpage>
<lpage>52</lpage>
<pub-id pub-id-type="doi">10.2188/jea.JE20150196</pub-id><pub-id pub-id-type="pmid">26972732</pub-id><pub-id pub-id-type="pmcid">PMC5037252</pub-id></element-citation>
</ref>
<ref id="B21">
<label>21</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Tamada</surname>
<given-names>Y</given-names>
</name>
<name>
<surname>Takeuchi</surname>
<given-names>K</given-names>
</name>
<name>
<surname>Yamaguchi</surname>
<given-names>C</given-names>
</name>
<name>
<surname>Saito</surname>
<given-names>M</given-names>
</name>
<name>
<surname>Ohira</surname>
<given-names>T</given-names>
</name>
<name>
<surname>Shirai</surname>
<given-names>K</given-names>
</name>
<etal>et al.</etal>
</person-group>
<article-title>Does laughter predict onset of functional disability and mortality among older Japanese adults? The JAGES prospective cohort study</article-title>
<source>J Epidemiol</source>
<year iso-8601-date="2021">2021</year>
<volume>31</volume>
<fpage>301</fpage>
<lpage>7</lpage>
<pub-id pub-id-type="doi">10.2188/jea.JE20200051</pub-id><pub-id pub-id-type="pmid">32418940</pub-id><pub-id pub-id-type="pmcid">PMC8021882</pub-id></element-citation>
</ref>
<ref id="B22">
<label>22</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Hirosaki</surname>
<given-names>M</given-names>
</name>
<name>
<surname>Ohira</surname>
<given-names>T</given-names>
</name>
<name>
<surname>Shirai</surname>
<given-names>K</given-names>
</name>
<name>
<surname>Kondo</surname>
<given-names>N</given-names>
</name>
<name>
<surname>Aida</surname>
<given-names>J</given-names>
</name>
<name>
<surname>Yamamoto</surname>
<given-names>T</given-names>
</name>
<etal>et al.</etal>
</person-group>
<article-title>Association between frequency of laughter and oral health among community-dwelling older adults: a population-based cross-sectional study in Japan</article-title>
<source>Qual Life Res</source>
<year iso-8601-date="2021">2021</year>
<volume>30</volume>
<fpage>1561</fpage>
<lpage>9</lpage>
<pub-id pub-id-type="doi">10.1007/s11136-020-02752-7</pub-id><pub-id pub-id-type="pmid">33432445</pub-id></element-citation>
</ref>
<ref id="B23">
<label>23</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Wang</surname>
<given-names>Y</given-names>
</name>
<name>
<surname>Shirai</surname>
<given-names>K</given-names>
</name>
<name>
<surname>Ohira</surname>
<given-names>T</given-names>
</name>
<name>
<surname>Hirosaki</surname>
<given-names>M</given-names>
</name>
<name>
<surname>Kondo</surname>
<given-names>N</given-names>
</name>
<name>
<surname>Takeuchi</surname>
<given-names>K</given-names>
</name>
<etal>et al.</etal>
</person-group>
<article-title>Occasions for laughter and dementia risk: findings from a six-year cohort study</article-title>
<source>Geriatr Gerontol Int</source>
<year iso-8601-date="2022">2022</year>
<volume>22</volume>
<fpage>392</fpage>
<lpage>8</lpage>
<pub-id pub-id-type="doi">10.1111/ggi.14371</pub-id><pub-id pub-id-type="pmid">35289045</pub-id></element-citation>
</ref>
<ref id="B24">
<label>24</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Sakurada</surname>
<given-names>K</given-names>
</name>
<name>
<surname>Konta</surname>
<given-names>T</given-names>
</name>
<name>
<surname>Watanabe</surname>
<given-names>M</given-names>
</name>
<name>
<surname>Ishizawa</surname>
<given-names>K</given-names>
</name>
<name>
<surname>Ueno</surname>
<given-names>Y</given-names>
</name>
<name>
<surname>Yamashita</surname>
<given-names>H</given-names>
</name>
<etal>et al.</etal>
</person-group>
<article-title>Associations of frequency of laughter with risk of all-cause mortality and cardiovascular disease incidence in a general population: findings from the Yamagata study</article-title>
<source>J Epidemiol</source>
<year iso-8601-date="2020">2020</year>
<volume>30</volume>
<fpage>188</fpage>
<lpage>93</lpage>
<pub-id pub-id-type="doi">10.2188/jea.JE20180249</pub-id><pub-id pub-id-type="pmid">30956258</pub-id><pub-id pub-id-type="pmcid">PMC7064551</pub-id></element-citation>
</ref>
<ref id="B25">
<label>25</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Hayashi</surname>
<given-names>F</given-names>
</name>
<name>
<surname>Shirai</surname>
<given-names>Y</given-names>
</name>
<name>
<surname>Ohira</surname>
<given-names>T</given-names>
</name>
<name>
<surname>Shirai</surname>
<given-names>K</given-names>
</name>
<name>
<surname>Kondo</surname>
<given-names>N</given-names>
</name>
<name>
<surname>Kondo</surname>
<given-names>K</given-names>
</name>
</person-group>
<article-title>Subjective happiness, frequency of laughter, and hypertension: a cross-sectional study based on the Japan Gerontological Evaluation Study (JAGES)</article-title>
<source>Int J Environ Res Public Health</source>
<year iso-8601-date="2023">2023</year>
<volume>20</volume>
<elocation-id>5713</elocation-id>
<pub-id pub-id-type="doi">10.3390/ijerph20095713</pub-id><pub-id pub-id-type="pmid">37174231</pub-id><pub-id pub-id-type="pmcid">PMC10178400</pub-id></element-citation>
</ref>
<ref id="B26">
<label>26</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Hayashi</surname>
<given-names>T</given-names>
</name>
<name>
<surname>Urayama</surname>
<given-names>O</given-names>
</name>
<name>
<surname>Kawai</surname>
<given-names>K</given-names>
</name>
<name>
<surname>Hayashi</surname>
<given-names>K</given-names>
</name>
<name>
<surname>Iwanaga</surname>
<given-names>S</given-names>
</name>
<name>
<surname>Ohta</surname>
<given-names>M</given-names>
</name>
<etal>et al.</etal>
</person-group>
<article-title>Laughter regulates gene expression in patients with type 2 diabetes</article-title>
<source>Psychother Psychosom</source>
<year iso-8601-date="2006">2006</year>
<volume>75</volume>
<fpage>62</fpage>
<lpage>5</lpage>
<pub-id pub-id-type="doi">10.1159/000089228</pub-id><pub-id pub-id-type="pmid">16361876</pub-id></element-citation>
</ref>
<ref id="B27">
<label>27</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Hayashi</surname>
<given-names>T</given-names>
</name>
<name>
<surname>Tsujii</surname>
<given-names>S</given-names>
</name>
<name>
<surname>Iburi</surname>
<given-names>T</given-names>
</name>
<name>
<surname>Tamanaha</surname>
<given-names>T</given-names>
</name>
<name>
<surname>Yamagami</surname>
<given-names>K</given-names>
</name>
<name>
<surname>Ishibashi</surname>
<given-names>R</given-names>
</name>
<etal>et al.</etal>
</person-group>
<article-title>Laughter up-regulates the genes related to NK cell activity in diabetes</article-title>
<source>Biomed Res</source>
<year iso-8601-date="2007">2007</year>
<volume>28</volume>
<fpage>281</fpage>
<lpage>5</lpage>
<pub-id pub-id-type="doi">10.2220/biomedres.28.281</pub-id><pub-id pub-id-type="pmid">18202517</pub-id></element-citation>
</ref>
<ref id="B28">
<label>28</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Kuru</surname>
<given-names>Alici N</given-names>
</name>
<name>
<surname>Arikan</surname>
<given-names>Dönmez A</given-names>
</name>
</person-group>
<article-title>A systematic review of the effect of laughter yoga on physical function and psychosocial outcomes in older adults</article-title>
<source>Complement Ther Clin Pract</source>
<year iso-8601-date="2020">2020</year>
<volume>41</volume>
<elocation-id>101252</elocation-id>
<pub-id pub-id-type="doi">10.1016/j.ctcp.2020.101252</pub-id><pub-id pub-id-type="pmid">33217706</pub-id></element-citation>
</ref>
<ref id="B29">
<label>29</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Ko</surname>
<given-names>HJ</given-names>
</name>
<name>
<surname>Youn</surname>
<given-names>CH</given-names>
</name>
</person-group>
<article-title>Effects of laughter therapy on depression, cognition and sleep among the community-dwelling elderly</article-title>
<source>Geriatr Gerontol Int</source>
<year iso-8601-date="2011">2011</year>
<volume>11</volume>
<fpage>267</fpage>
<lpage>74</lpage>
<pub-id pub-id-type="doi">10.1111/j.1447-0594.2010.00680.x</pub-id><pub-id pub-id-type="pmid">21241447</pub-id></element-citation>
</ref>
<ref id="B30">
<label>30</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Elsayed</surname>
<given-names>MM</given-names>
</name>
<name>
<surname>Nagy</surname>
<given-names>EN</given-names>
</name>
</person-group>
<article-title>Effectiveness of aerobic exercise with laughter therapy on functional, cognitive, and psychological well-being in the elderly: a randomized controlled clinical trial</article-title>
<source>Egypt J Hosp Med</source>
<year iso-8601-date="2023">2023</year>
<volume>90</volume>
<fpage>241</fpage>
<lpage>7</lpage>
</element-citation>
</ref>
<ref id="B31">
<label>31</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Armat</surname>
<given-names>MR</given-names>
</name>
<name>
<surname>Emami</surname>
<given-names>Zeydi A</given-names>
</name>
<name>
<surname>Mokarami</surname>
<given-names>H</given-names>
</name>
<name>
<surname>Nakhlband</surname>
<given-names>A</given-names>
</name>
<name>
<surname>Hojjat</surname>
<given-names>SK</given-names>
</name>
</person-group>
<article-title>The impact of laughter yoga on depression and anxiety among retired women: a randomized controlled clinical trial</article-title>
<source>J Women Aging</source>
<year iso-8601-date="2022">2022</year>
<volume>34</volume>
<fpage>31</fpage>
<lpage>42</lpage>
<pub-id pub-id-type="doi">10.1080/08952841.2020.1774225</pub-id><pub-id pub-id-type="pmid">32552530</pub-id></element-citation>
</ref>
<ref id="B32">
<label>32</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Morishima</surname>
<given-names>T</given-names>
</name>
<name>
<surname>Miyashiro</surname>
<given-names>I</given-names>
</name>
<name>
<surname>Inoue</surname>
<given-names>N</given-names>
</name>
<name>
<surname>Kitasaka</surname>
<given-names>M</given-names>
</name>
<name>
<surname>Akazawa</surname>
<given-names>T</given-names>
</name>
<name>
<surname>Higeno</surname>
<given-names>A</given-names>
</name>
<etal>et al.</etal>
</person-group>
<article-title>Effects of laughter therapy on quality of life in patients with cancer: an open-label, randomized controlled trial</article-title>
<source>PLoS One</source>
<year iso-8601-date="2019">2019</year>
<volume>14</volume>
<elocation-id>e0219065</elocation-id>
<pub-id pub-id-type="doi">10.1371/journal.pone.0219065</pub-id><pub-id pub-id-type="pmid">31247017</pub-id><pub-id pub-id-type="pmcid">PMC6597115</pub-id></element-citation>
</ref>
<ref id="B33">
<label>33</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Funakubo</surname>
<given-names>N</given-names>
</name>
<name>
<surname>Eguchi</surname>
<given-names>E</given-names>
</name>
<name>
<surname>Hayashi</surname>
<given-names>R</given-names>
</name>
<name>
<surname>Hirosaki</surname>
<given-names>M</given-names>
</name>
<name>
<surname>Shirai</surname>
<given-names>K</given-names>
</name>
<name>
<surname>Okazaki</surname>
<given-names>K</given-names>
</name>
<etal>et al.</etal>
</person-group>
<article-title>Effects of a laughter program on body weight and mental health among Japanese people with metabolic syndrome risk factors: a randomized controlled trial</article-title>
<source>BMC Geriatr</source>
<year iso-8601-date="2022">2022</year>
<volume>22</volume>
<elocation-id>361</elocation-id>
<pub-id pub-id-type="doi">10.1186/s12877-022-03038-y</pub-id><pub-id pub-id-type="pmid">35461239</pub-id><pub-id pub-id-type="pmcid">PMC9035242</pub-id></element-citation>
</ref>
<ref id="B34">
<label>34</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Noureldein</surname>
<given-names>MH</given-names>
</name>
<name>
<surname>Eid</surname>
<given-names>AA</given-names>
</name>
</person-group>
<article-title>Homeostatic effect of laughter on diabetic cardiovascular complications: the myth turned to fact</article-title>
<source>Diabetes Res Clin Pract</source>
<year iso-8601-date="2018">2018</year>
<volume>135</volume>
<fpage>111</fpage>
<lpage>9</lpage>
<pub-id pub-id-type="doi">10.1016/j.diabres.2017.11.014</pub-id><pub-id pub-id-type="pmid">29162513</pub-id></element-citation>
</ref>
<ref id="B35">
<label>35</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Gonot-Schoupinsky</surname>
<given-names>F</given-names>
</name>
<name>
<surname>Garip</surname>
<given-names>G</given-names>
</name>
<name>
<surname>Sheffield</surname>
<given-names>D</given-names>
</name>
</person-group>
<article-title>The engage-disengage model as an inclusive model for the promotion of healthy and successful aging in the oldest-old</article-title>
<source>Act Adapt Aging</source>
<year iso-8601-date="2022">2022</year>
<volume>46</volume>
<fpage>159</fpage>
<lpage>81</lpage>
</element-citation>
</ref>
<ref id="B36">
<label>36</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Wagner</surname>
<given-names>H</given-names>
</name>
<name>
<surname>Rehmes</surname>
<given-names>U</given-names>
</name>
<name>
<surname>Kohle</surname>
<given-names>D</given-names>
</name>
<name>
<surname>Puta</surname>
<given-names>C</given-names>
</name>
</person-group>
<article-title>Laughing: a demanding exercise for trunk muscles</article-title>
<source>J Mot Behav</source>
<year iso-8601-date="2014">2014</year>
<volume>46</volume>
<fpage>33</fpage>
<lpage>7</lpage>
<pub-id pub-id-type="doi">10.1080/00222895.2013.844091</pub-id><pub-id pub-id-type="pmid">24246140</pub-id></element-citation>
</ref>
<ref id="B37">
<label>37</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Miller</surname>
<given-names>M</given-names>
</name>
<name>
<surname>Fry</surname>
<given-names>WF</given-names>
</name>
</person-group>
<article-title>The effect of mirthful laughter on the human cardiovascular system</article-title>
<source>Med Hypotheses</source>
<year iso-8601-date="2009">2009</year>
<volume>73</volume>
<fpage>636</fpage>
<lpage>9</lpage>
<pub-id pub-id-type="doi">10.1016/j.mehy.2009.02.044</pub-id><pub-id pub-id-type="pmid">19477604</pub-id><pub-id pub-id-type="pmcid">PMC2814549</pub-id></element-citation>
</ref>
<ref id="B38">
<label>38</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Berk</surname>
<given-names>LS</given-names>
</name>
<name>
<surname>Tan</surname>
<given-names>SA</given-names>
</name>
<name>
<surname>Fry</surname>
<given-names>WF</given-names>
</name>
<name>
<surname>Napier</surname>
<given-names>BJ</given-names>
</name>
<name>
<surname>Lee</surname>
<given-names>JW</given-names>
</name>
<name>
<surname>Hubbard</surname>
<given-names>RW</given-names>
</name>
<etal>et al.</etal>
</person-group>
<article-title>Neuroendocrine and stress hormone changes during mirthful laughter</article-title>
<source>Am J Med Sci</source>
<year iso-8601-date="1989">1989</year>
<volume>298</volume>
<fpage>390</fpage>
<lpage>6</lpage>
<pub-id pub-id-type="doi">10.1097/00000441-198912000-00006</pub-id><pub-id pub-id-type="pmid">2556917</pub-id></element-citation>
</ref>
<ref id="B39">
<label>39</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Kramer</surname>
<given-names>CK</given-names>
</name>
<name>
<surname>Leitao</surname>
<given-names>CB</given-names>
</name>
</person-group>
<article-title>Laughter as medicine: a systematic review and meta-analysis of interventional studies evaluating the impact of spontaneous laughter on cortisol levels</article-title>
<source>PLoS One</source>
<year iso-8601-date="2023">2023</year>
<volume>18</volume>
<elocation-id>e0286260</elocation-id>
<pub-id pub-id-type="doi">10.1371/journal.pone.0286260</pub-id><pub-id pub-id-type="pmid">37220157</pub-id><pub-id pub-id-type="pmcid">PMC10204943</pub-id></element-citation>
</ref>
<ref id="B40">
<label>40</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Shannon</surname>
<given-names>OM</given-names>
</name>
<name>
<surname>Clifford</surname>
<given-names>T</given-names>
</name>
<name>
<surname>Seals</surname>
<given-names>DR</given-names>
</name>
<name>
<surname>Craighead</surname>
<given-names>DH</given-names>
</name>
<name>
<surname>Rossman</surname>
<given-names>MJ</given-names>
</name>
</person-group>
<article-title>Nitric oxide, aging and aerobic exercise: sedentary individuals to Master’s athletes</article-title>
<source>Nitric Oxide</source>
<year iso-8601-date="2022">2022</year>
<volume>125–6</volume>
<fpage>31</fpage>
<lpage>9</lpage>
<pub-id pub-id-type="doi">10.1016/j.niox.2022.06.002</pub-id><pub-id pub-id-type="pmid">35705144</pub-id></element-citation>
</ref>
<ref id="B41">
<label>41</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Vasto</surname>
<given-names>S</given-names>
</name>
<name>
<surname>Scapagnini</surname>
<given-names>G</given-names>
</name>
<name>
<surname>Bulati</surname>
<given-names>M</given-names>
</name>
<name>
<surname>Candore</surname>
<given-names>G</given-names>
</name>
<name>
<surname>Castiglia</surname>
<given-names>L</given-names>
</name>
<name>
<surname>Colonna-Romano</surname>
<given-names>G</given-names>
</name>
<etal>et al.</etal>
</person-group>
<article-title>Biomarkes of aging</article-title>
<source>Front Biosci (Schol Ed)</source>
<year iso-8601-date="2010">2010</year>
<volume>2</volume>
<fpage>392</fpage>
<lpage>402</lpage>
<pub-id pub-id-type="doi">10.2741/s72</pub-id><pub-id pub-id-type="pmid">20036955</pub-id></element-citation>
</ref>
<ref id="B42">
<label>42</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Berk</surname>
<given-names>LS</given-names>
</name>
<name>
<surname>Tan</surname>
<given-names>S</given-names>
</name>
</person-group>
<article-title>Mirthful laughter, as adjunct therapy in diabetic care, increases HDL cholesterol and attenuates inflammatory cytokines and C‐RP and possible CVD risk</article-title>
<source>FASEB J</source>
<year iso-8601-date="2009">2009</year>
<volume>23</volume>
<elocation-id>990.1</elocation-id>
<pub-id pub-id-type="doi">10.1096/fasebj.23.1_supplement.990.1</pub-id></element-citation>
</ref>
<ref id="B43">
<label>43</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Bains</surname>
<given-names>G</given-names>
</name>
<name>
<surname>Berk</surname>
<given-names>L</given-names>
</name>
<name>
<surname>Lohman</surname>
<given-names>E</given-names>
</name>
<name>
<surname>Daher</surname>
<given-names>N</given-names>
</name>
<name>
<surname>Miranda</surname>
<given-names>B</given-names>
</name>
</person-group>
<article-title>Decrease in inflammation (CRP) and heart rate through mirthful laughter</article-title>
<source>FASEB J</source>
<year iso-8601-date="2017">2017</year>
<volume>31</volume>
<elocation-id>697.7</elocation-id>
<pub-id pub-id-type="doi">10.1096/fasebj.31.1_supplement.697.7</pub-id></element-citation>
</ref>
<ref id="B44">
<label>44</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Gonot-Schoupinsky</surname>
<given-names>FN</given-names>
</name>
<name>
<surname>Garip</surname>
<given-names>G</given-names>
</name>
</person-group>
<article-title>Laughter and humour interventions for well-being in older adults: a systematic review and intervention classification</article-title>
<source>Complement Ther Med</source>
<year iso-8601-date="2018">2018</year>
<volume>38</volume>
<fpage>85</fpage>
<lpage>91</lpage>
<pub-id pub-id-type="doi">10.1016/j.ctim.2018.04.009</pub-id><pub-id pub-id-type="pmid">29857886</pub-id></element-citation>
</ref>
<ref id="B45">
<label>45</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Miller</surname>
<given-names>A</given-names>
</name>
<name>
<surname>Pratt</surname>
<given-names>H</given-names>
</name>
<name>
<surname>Schiffer</surname>
<given-names>RB</given-names>
</name>
</person-group>
<article-title>Pseudobulbar affect: the spectrum of clinical presentations, etiologies and treatments</article-title>
<source>Expert Rev Neurother</source>
<year iso-8601-date="2011">2011</year>
<volume>11</volume>
<fpage>1077</fpage>
<lpage>88</lpage>
<pub-id pub-id-type="doi">10.1586/ern.11.68</pub-id><pub-id pub-id-type="pmid">21539437</pub-id></element-citation>
</ref>
<ref id="B46">
<label>46</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Ferner</surname>
<given-names>RE</given-names>
</name>
<name>
<surname>Aronson</surname>
<given-names>JK</given-names>
</name>
</person-group>
<article-title>Laughter and MIRTH (methodical investigation of risibility, therapeutic and harmful): narrative synthesis</article-title>
<source>BMJ</source>
<year iso-8601-date="2013">2013</year>
<volume>347</volume>
<elocation-id>f7274</elocation-id>
<pub-id pub-id-type="doi">10.1136/bmj.f7274</pub-id><pub-id pub-id-type="pmid">24336308</pub-id><pub-id pub-id-type="pmcid">PMC3898427</pub-id></element-citation>
</ref>
<ref id="B47">
<label>47</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Rotton</surname>
<given-names>J</given-names>
</name>
</person-group>
<article-title>Trait humor and longevity: Do comics have the last laugh?</article-title>
<source>Health Psychol</source>
<year iso-8601-date="1992">1992</year>
<volume>11</volume>
<fpage>262</fpage>
<lpage>6</lpage>
<pub-id pub-id-type="doi">10.1037//0278-6133.11.4.262</pub-id><pub-id pub-id-type="pmid">1396495</pub-id></element-citation>
</ref>
<ref id="B48">
<label>48</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Gonot-Schoupinsky</surname>
<given-names>FN</given-names>
</name>
<name>
<surname>Garip</surname>
<given-names>G</given-names>
</name>
<name>
<surname>Sheffield</surname>
<given-names>D</given-names>
</name>
</person-group>
<article-title>Laughter and humour for personal development: a systematic scoping review of the evidence</article-title>
<source>Eur J Integr Med</source>
<year iso-8601-date="2020">2020</year>
<volume>37</volume>
<elocation-id>101144</elocation-id>
<pub-id pub-id-type="doi">10.1016/j.eujim.2020.101144</pub-id></element-citation>
</ref>
<ref id="B49">
<label>49</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Platt</surname>
<given-names>T</given-names>
</name>
<name>
<surname>Ruch</surname>
<given-names>W</given-names>
</name>
<name>
<surname>Proyer</surname>
<given-names>RT</given-names>
</name>
</person-group>
<article-title>A lifetime of fear of being laughed at: an aged perspective</article-title>
<source>Z Gerontol Geriatr</source>
<year iso-8601-date="2010">2010</year>
<volume>43</volume>
<fpage>36</fpage>
<lpage>41</lpage>
<pub-id pub-id-type="doi">10.1007/s00391-009-0083-z</pub-id><pub-id pub-id-type="pmid">20013341</pub-id></element-citation>
</ref>
<ref id="B50">
<label>50</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Puca</surname>
<given-names>AA</given-names>
</name>
<name>
<surname>Spinelli</surname>
<given-names>C</given-names>
</name>
<name>
<surname>Accardi</surname>
<given-names>G</given-names>
</name>
<name>
<surname>Villa</surname>
<given-names>F</given-names>
</name>
<name>
<surname>Caruso</surname>
<given-names>C</given-names>
</name>
</person-group>
<article-title>Centenarians as a model to discover genetic and epigenetic signatures of healthy ageing</article-title>
<source>Mech Ageing Dev</source>
<year iso-8601-date="2018">2018</year>
<volume>174</volume>
<fpage>95</fpage>
<lpage>102</lpage>
<pub-id pub-id-type="doi">10.1016/j.mad.2017.10.004</pub-id><pub-id pub-id-type="pmid">29096878</pub-id></element-citation>
</ref>
<ref id="B51">
<label>51</label>
<element-citation publication-type="journal">
<person-group person-group-type="author">
<name>
<surname>Longo</surname>
<given-names>VD</given-names>
</name>
<name>
<surname>Antebi</surname>
<given-names>A</given-names>
</name>
<name>
<surname>Bartke</surname>
<given-names>A</given-names>
</name>
<name>
<surname>Barzilai</surname>
<given-names>N</given-names>
</name>
<name>
<surname>Brown-Borg</surname>
<given-names>HM</given-names>
</name>
<name>
<surname>Caruso</surname>
<given-names>C</given-names>
</name>
<etal>et al.</etal>
</person-group>
<article-title>Interventions to slow aging in humans: Are we ready?</article-title>
<source>Aging Cell</source>
<year iso-8601-date="2015">2015</year>
<volume>14</volume>
<fpage>497</fpage>
<lpage>510</lpage>
<pub-id pub-id-type="doi">10.1111/acel.12338</pub-id><pub-id pub-id-type="pmid">25902704</pub-id><pub-id pub-id-type="pmcid">PMC4531065</pub-id></element-citation>
</ref>
</ref-list>
</back>
</article>