So my name is Van Keeley and I'm currently a clinical professor at Department of Psychiatry and Behavioral Sciences at School of Medicine, Stanford University. So today my talk will be on behalf of NIA funded new Brain Aging Center. I'm going to talk about one end of the spectrum of aging and resilience research focusing on cross-species-guided brain behavior research. In today's talk, I will cover three main sections. Firstly... It's a little bit too loud. Oh, too loud. Okay. So let me be a little far away. Is this better? Yeah. Okay. Thanks. Okay. So firstly, I will provide a brief overview of the resilience theories, and secondly, I will discuss the importance of utilizing comparable cross-species models to study brain behavior relationships in the context of aging and resilience. And lastly, I will illustrate how our new Brain Aging Center is working to promote resilience and aging research using cross-species models. This figure here illustrates a recent definition of resilience from NIH. Resilience is a complex concept that involves multiple factors, including challenges, system, and response. A system's response to challenges can vary greatly. Outcomes of resilience reflect a system's ability to maintain, return to, or improve from its baseline measures. Resilience can be maintained through adaptation, but is reduced when a system only partially recovers from a challenge, and it is lost completely if the system fails to recover at all. And these dynamics continue to evolve over time. Together, these aspects shape the overall concept of resilience. In the following talk, I will focus on the brain behavior adaptation to studying resilience. The tripartite model of resilience building takes an effective neuroscience approach and proposes three distinct categories of strategies that contribute to growing resilience. They are upregulating the positive, downregulating the negative, and transcending the self. Both strategies are somehow related to the function of the prefrontal cortex, but some networks seem to support specific strategies. For example, transcending the self is related to change in the deformal network. Downregulating the negative is related to amygdala, HPA, and autonomic nervous system, while upregulating the positive is related to the straight-8 reward networks. Apart from the central nervous system, the HPA and autonomic nervous system mentioned earlier, the immune system and the change in gut microbiome composition and the blood-brain barrier all play a crucial role in shaping our responses to stress and promoting resilience. Understanding the interaction between these components is key to unraveling the complex mechanisms underlying stress resilience. Cumulated animal models have shown pyramidal neurons in the medial prefrontal cortex display profound behaviorally-induced negative plasticity, meaning the shrinkage and the loss of spines with stress, as well as the capacity to recover from stress, meaning the neuronal resilience. However, aging processes affect neuronal resilience in several aspects. The example A here is about dendrites. In young animals, chronic stress leads to shrinkage of dendrites. After cessation of chronic stress, dendritic trees regrow. Such neuronal resilience is blunted in middle age and further diminished in old age. Example B here is about loss of thin spine as ages. Human studies suggest a similar complexity of aging effect on resilience and brain integrity. This is an example from PTSD. Older adults who are resilient to stress have larger parahippocampus compared to those chronologically suffering from PTSD. And the result, however, is opposite from what found in younger adults. So in summary, aging factors, both chronologically and biological aging, may interact with resilience process in influencing functional health or well-being. Understanding the mechanisms between biological aging, resilience process, and the functional health or well-being is crucial in studying resiliency in aging. Intervention may be developed accordingly. However, we can't fully establish directionality or causality by using human models alone. Cross-species approach may help specify mechanisms of resiliency in aging. Before discussing examples of cross-species models for guiding aging and the resilient research from our center, I would like to emphasize the importance of comparability-related methods in these studies. One commonly used form of comparability in cross-species aging research is the comparison of age across species. This serves as the foundation for studying the inference of chronological aging on various conditions. However, achieving comparability in terms of brain aging or other biological processes is more complex and has received less attention. To address this, I will introduce four categories of comparability. So now, comparability in brain meshes, behavior meshes, research methods for studying brain behavior relationships, and the contextual factors. In human brain imaging, the focus has predominantly been on marker levels. Animal brain imaging, on the other hand, provides insight into a full spectrum, which offers useful understanding of precise neuronal mechanisms underlying marker-level findings in humans. To ensure effective cross-species brain comparison, a three-step comparison approach has been proposed. Taking different scales of brain imaging as an example, these three steps involve examining muscle marker imaging modalities within the same species, the marker-level imaging across different species, and finally, the muscle-level imaging in animals and the marker-level imaging in humans. However, merely discussing a comparable imaging modality or study design is not sufficient. We must consider a comparable brain imaging analytical approach as well. Traditional methods involve identifying comparable functional regions or circuits that serve similar functional purposes across species. For example, the slide here shows an example of amygdala and its circuit studied for this manner. More recent work has been focusing on the reconstruction of brain connectomes across species. This involves converting whole brain connectome maps into graph maps and studying the functional characteristics of these graphs. This approach holds promise for discovering unknown robust brain regions or circuits that are functionally similar to humans. It forms the basis for identifying novel brain targets for manipulation in animal models. Equally important but more controversial is the comparability of cross-species behaviors. By using computational modeling, it becomes more feasible to increase the comparison of behaviors in different dimensions. For example, we can compare a single behavior in temporal and spatial dimensions. The example here is about gait and mobility. Behavior can also encompass multiple behavior modes. For instance, the expression of emotion can be modeled through multiple comparable behavior modes across species, such as violence, persistence, intensities, and others. When studying the relationship between brain and the behavior across species, it is often more practical to anchor the comparability on a specific domain. As an example, we can explore the comparability of hallucination or hallucination-like perception across species while confirming the underlying brain mechanisms within each species. This may provide a more reliable way for understanding any overlap of brain mechanisms underlying similar behaviors across species. The final category of comparability is related to contextual factors, which can include stressors. The common way of comparison of stressors across species are hallmarks of brain and other biological aging factors. And the less common way are psychosocial stressors, like social isolation, change in cognitive control, these kind of models. And the second is manipulation procedure. This enriched environment probably is the most classical example of the manipulation format that has been studied in both non-human animals and the human model, including the older dogs. And finally is the environmental factor. And the more common way has been studied historically on the laboratory and the cage environment, and the less commonly studied on the real world or naturalistic environment, which is kind of an emerging field at this point due to the computational modelings of growth as well. So in summary, it is crucial to pay attention to cross-species comparability in terms of brain imaging behavior, brain behavior relationships, and contextual factors. This foundation allows us to study the specific mechanisms underlying resilience in aging. As we reach in the final section of the presentation, I will now discuss how our work and the new Brain Aging Center by combining the theoretical and the biological backgrounds on resilience and aging within the cross-species comparability method as this previous described. So the new Brain Aging Center is an NIA-funded U24 initiative that focuses on promoting research on brain aging and emotional well-being using a cross-species model. Emotional well-being is a multi-dimensional composite that encompasses how positive an individual feels generally and about life overall. It has both experiential features such as emotional quality of momentary everyday experience as well as reflective features such as judgment about life, life satisfaction, and meaning of life. Our research explores two main directions. On one hand, we try to understand how brain aging processes influence emotional well-being. And on the other hand, we try to investigate how emotional well-being can protect older adults against brain aging. We leverage animal models to understand and manipulate the precise neural pathways underlying these two directions with a particular emphasis on resilience-related appraisal and adaptation pathways. Emotional well-being is a very complex function, but the neural pathways involved in adaptation and reappraisal are comparable across species. The slide presented here shows examples of comparable liking and discussed reactions across species in younger individuals, along with the neural circuits that underline these reactions. Building upon these findings, we propose comparable adaptation and reappraisal processes across species in older age that are related to emotional well-being research. We are particularly interested in affective stimuli and the behavior and the physiological paradigms that assess reactivity and reappraisal in relation to emotional processes. The comparability is largely relying on knowing neural mechanisms about shared across species in these behaviors. However, how well or precise in a context these behaviors align across species, we need to test in case by case. To better understand emotional well-being, we have developed a reactivity and a reappraisal framework by synthesizing literature on emotional processing and the underlying brain circuit mechanism in human and non-human animals. Our model emphasizes the dynamic interaction between affective stimuli, autonomic responses, brain emotional states, and subjective feelings. It integrates a unique emotional process involved in explaining emotional well-being in aging humans with an emerging mechanism of topologically conserved emotional brain networks from cross-species studies. Along with what I described in the first section of studying aging and the resilience interaction on function and the well-being, our center studies the reactivity and reappraisal framework as a resilient model, and its interaction with brain aging for understanding reflected in the experience emotional well-being. Considering the role of resilience in brain aging and the functional health, our center is interested in both the animal to human translation of brain mechanistic insights, which include the developing and the testing in-depth measurement and the causal manipulation to identify changes and the determined direction of interactions, as well as the evaluated component of, as well as the human to animal translation of the objective model of emotional well-being components, meaning we are particularly interested in understanding how this evaluative component in human studies may be translated to be objectively evaluated in animal model through the enriched environment and the social experience. So based on this framework and our targeted interest, we have funded a six-part project and a diverse supplement fellowship from four institutes related to brain aging and emotional well-being. These studies contribute to potentially comparable measures for behaviors in naturalistic environments, novel brain imaging methods, and the understanding of brain behavior mechanisms related to emotional well-being. So in summary, we propose a reactivity reappraisal framework for studying the relationship between emotional well-being and the brain aging. By synthesizing the findings from our pilot study, we plan to propose two new directions for our center's renewal, which will be occurring very soon, focusing on developing new brain plasticity-oriented interventions to promote emotional well-being in old adults with neuropsychiatric symptoms and others, as well as to develop interventions targeting emotional well-being to slow down or prevent brain aging. So in conclusion, I would like to express my gratitude to our center's executive committee, advisory board, and IA science officer, and the administrative support for these invaluable contributions. I hope the topic of emotional well-being has captured the interest of an audience, particularly in relation to its application for studying resilience and aging. The emphasis on comparability in cross-species research provides a novel approach to understand the mechanism and identify intervention that collect the emotional well-being and the brain aging. Additionally, I am very excited to announce we will soon release our fourth-year pilot and offer travel fellowship to our workshop, which will be held as part of the Society for Neuroscience Conference in November. So please do not hesitate to reach out to us if you are interested in learning more about the various opportunities, and we are also looking forward to future collaboration with the psychiatric community here. Thank you. Any quick questions for Venky? So, as you now understand, we composed this symposium to start with preclinical studies. And I'll be speaking about clinical studies and applications to clinical practice. And Dr. Jesti will follow up with community-based interventions enhancing resilience and well-being. And we represent a new line of thinking within the field. And actually, you know, many countries are getting on the same wavelengths in terms of the importance of promoting resilience in aging. Particularly because there's an overwhelming aging of the population and no healthcare system around the world, no government can sustain the numbers, the sheer numbers of older adults who typically have chronic conditions. This is my disclosure slide, along with the books on resilience and aging. So I'll talk about resilience and aging trends, describe biomarkers of psychological resilience and application to clinical practice, discuss studies of resilience building interventions in older adults, and biomarkers of response to my body. And that's what I was talking about. That's a hard problem. As you see, there's a crossover between older adults exponentially increasing in number around the world, and decline in children under five. So we're not going to have enough caregivers who would take care of all of us who are getting older. And this is a chronic stress curve in response to mass disasters. And as you know, we have plenty of those, climate-related, pandemic-related, war-related, migration-related, all sorts of chronic stress condition. And so we're dealing with an aging population that is chronically stressed. So there are just not enough of mental health professionals to take care of everybody. And I think mental health is on everybody's mind. Psychological factors specific to aging are stressors like chronic illness, cognitive decline, caregiving, financial stressors, loss of independence, loneliness, and bereavement. Of course, a stress of dealing with stigma and stereotypes surrounding aging, especially in this society that is youth-worshipping and oriented, social role and identity changes such as retirement, widowhood, loss of independence, and of course, cognitive changes with aging, decline in processing speed, certain memory language, visual, spatial, and executive function abilities. However, emotional regulation improves with age. Basically, people stop paying attention to small things. Don't sweat the small stuff. And resilience improves with age. The reality of us living in a very stressed world is that one out of five people in the United States has a mental illness in 2019. And it's much higher at this point simply because pandemic raised levels of anxiety and depression, substance abuse, and suicides. Compared to 11% of adults having anxiety, reporting anxiety pre-COVID, it is at this point between 30% and 40%. And it has not dipped too much. More than 150 million people live in federal designated mental health professional shortage areas. And this is the reality of older adults experienced through the pandemic. First of all, the level of anxiety increased, and the services were cut down. Many units and services, mental health services, were converted into COVID units. And the only thing that flourished was telehealth, and it continues to be the truth. And in fact, it improved access to care in many instances, especially for long COVID patients who don't travel and older adults as well. It also created an outlet for loneliness epidemic that came with isolation. Another fact is that long COVID syndrome, which is a lasting neuropsychiatric symptoms last after a COVID infection, has prevalence of between 10% to 30%. Among those, new onset occurs in 10% to 20%. And the symptoms that are prevalent are fatigue, brain fog, and cognitive impairment, chronic malaise, anxiety, depression, PTSD, increased suicidality, psychosis, and delirium. And in older adults who had COVID and had pre-existing mild cognitive impairment, switch to dementia is quite common. So as I mentioned, the trends for the next decade are global aging, with 40% increased mortality and 15% increase in disabilities. Mental health crisis with accelerated mass disasters of all sorts, quite quitting among frontline workers and just in general due to burnout, early retirement, geopolitical migration. However, that opened an opportunity for innovation, sustainable delivery of care through telemedicine, role of new health technologies like AI, changing healthcare systems into primordial and primary prevention enterprise, whole person healthcare, and the pushes in sheer numbers of people who need this and not having enough providers. In addition, even before COVID, World Health Organization announced this decade to be the decade of healthy aging. And in 2019, they called for dementia care for innovation that promotes brain health and well-being. So all of a sudden, everybody around the world is interested in interventions that an understanding that would prevent diseases of aging, including neurocognitive and neuropsychiatric disorders of aging, understanding that we could start as early as conception. So because maternal transmission of trauma occurs in utero and any toxic exposures occur in utero, we don't become vulnerable to disease when we reach age of 55. It happens throughout the life and in early childhood exposures with early adolescence and young adulthood, head traumas, toxicities, drug use, alcohol use would lead to accelerated morbidity with disorders of aging. And so early interventions at this age or as early as possible would help prevent disorders of aging. So here, well-being, the concept of well-being really is defined as a multi-component concept of mental, emotional, physical, social, environmental, spiritual well-being. And it's a core outcome of interest for many interventions right now. And it's important for patients with mental and physical disorders and those who are at risk for developing those. It's a core concept of positive psychiatry with the assessment focused on positive attributes and strengths rather than symptoms of depression or anxiety or any others. Research is focused on protective factors and psycho and neuroplasticity. Treatment goals become achievement of recovery, well-being, successful aging, post-traumatic growth. And treatments include psychosocial, behavioral, biological interventions to enhance positive attributes. And prevention occurs across lifespan. This is the definition of resilience. What is it from famous people? Confucius said, our greatest glory is not in never falling, but in rising every time we fall. Winston Churchill, success is not final, failure is not fatal. It is the courage to continue that counts. And Amanda Ripley really described it very helpfully for our purposes. Resilience is a precious skill. People who have it tend to also have three underlying advantages. A belief that they can influence life events, a tendency to find meaningful purpose in life, turmoil, and a conviction that they can learn from both positive and negative experiences. So as Venky said, there's a dynamic characteristic of the interaction between the individual and their environment's ability to recover from adversity, trauma, stress, depression. The question is, and NIH is struggling with this in defining resilience, does it require a major traumatic experience to manifest? And I have to tell, as a geriatric psychiatrist, it's just day-to-day survival in older adults, whether it's getting groceries or medications or getting to the doctor, figuring out details of getting to the doctor's appointments. This construct can be fostered in younger and older adults and would lead to effective and positive coping with stress. Generally, the main principle is that you can turn adversity into the opportunity to, for growth, to learn and grow from. Consequently, it would lead to better outcomes for medical and mental disorders of aging. The historical perspective on resilience was that you're born with this trait. You're either resilient or you're not. And depression is a resiliency deficiency opposite to resilience. However, in more recent perspectives, resilience can vary across the lifespan. And again, as you get older, you become more resilient. Resilience varies substantially even among those who are clinically depressed or have schizophrenia or any other mental illness. So you could build on that in your patients who do have some symptoms, but they also have strengths. So it's evaluation of their strengths. The biomarkers of resilience have been addressed at multiple levels of stress response. Recent studies demonstrated neural substrates, including prefrontal cortex, hippocampus, amygdala, anterior cingulate forming the pathway for resilience. However, what never happened, hyperintensities, which is a hallmark of cerebrovascular disease and neurodegeneration, become risk factors undermining resilience. On the hormonal axis, cortisol and DHEA are substances that are assigned to stress response and inflammatory mediators as well that may constitute a link between lifestyle factors, infection and physiological changes of aging, on the one hand, and risk factors for age-associated diseases on the other. Could surface targets or biomarkers of resilience in investigating resilience-building interventions. Substances like brain-derived neurotrophic factor, BDNF, or neuropeptide white, and neuroplasticity factors become protective factors. Also genetic composition makeup, like APOE4 carriership, would lead to undermining resilience of the brain and mind, and other COMT variations would be protective or risk factors. Resilience falls really into the model of stress and health, where we all are evolutionally built, our bodies and brains are built to handle chronic stress, but it's shaped by our experiences, like environmental stressors or toxicities, exposure to trauma and abuse, individual differences in genetics, and also our choices in lifestyle, like sleep, diet, exercise, drug use, alcohol use, which shape our stress response. So our bodies are built to handle chronic stress through adaptation, and that process refers to as allostasis, leading to adaptation. The body is able to maintain stability in the face of adversity or change. But then when stress becomes too chronic or too much for us, it leads to maladaptive response allostatic load. And the symptoms of allostatic load are hypertension, obesity, high levels of cholesterol, and bad lipids and decline in good lipids, like HDL, increase in blood sugars, increase in cortisol, norepinephrine, epinephrine, and a decline in DHES, which is also a protective factor. So if you think about it, those are disorders of aging, hypertension, obesity, hypercholesterolemia, diabetes, and that's what the price of aging is, leading to this chronic diseases of aging. So the stress response, biological stress response, is shaped by the interaction between brain, CNS, autonomic nervous system, neuroendocrine and immune systems, with multiple chemicals and inflammatory markers interacting within each other. And they can be tracked while you're doing interventions in order to understand neurobiology of why things are working or not working. With aging also, as I mentioned, cerebrovascular disease, neurodegeneration, chronic inflammation create this condition for vulnerable brain when during stress it could tip over into depression or any other psychiatric disorders. However, we also know protective factors such as social support and participation, physical and cognitive activities, and brain reserve and factors that contribute to brain reserve. On MRI scan or CT scan, structural imaging, you could see these white dots around ventricles or in the white matter or gray matter here that signifies cerebrovascular disease, which is commonly seen in geriatric depression, schizophrenia, or cognitive disorders. This is nonspecific and related to aging processes. Also biomarkers of the mechanism of biological aging include epigenetic alterations, genomic instability, mitochondrial dysfunction, cellulose senescence, chronic inflammation, loss of proteostasis, and telomere attrition. And this is the biology of aging and gerocides, referred to as gerocides, we understand biological aging through gerocides. And gerocides-informed interventions can rebuild or reverse some of the biological aging. And you may know about well-known effects of exercise or dietary interventions like anti-inflammatory diet or microbiome, the use of nutraceuticals like vitamin D or fish oil or vitamin B supplementation and hormonal supplementation in aging that could be helpful. Also drugs like metformin have well-documented anti-aging effects. We've published a number of papers on resilience in late-life depression where we try to dissect from our available samples biomarkers of resilience, understanding demographic clinical variables, neurobiology, and subsequent remission of depressive symptoms. So we had a combined sample of 337 adults who were age 60 with major depressive disorder known as dementia. And we used a factor analysis to understand the data. We used a corner data resilience scale which is a 25 item, 100 is a top score of it. Also geriatric depression scale, Hamilton depression rating scale, anxiety scale, apathy evaluation scale, cumulative illness rating scale that measures medical burden, cerebrovascular risk on CBRS, and then quality of life, enjoyment and satisfaction or health-related quality of life as F36 scale. And so the majority were female, mostly white, and then age 70 and mid-age and well-educated education of 15.8 years, not demented, moderately depressed on GDS and Hamilton depression scale. And you can't really see well the questions, but this is Connor Davidson resilience scale. The point is that we were able to derive three factors, greed, coping, self-efficacy, accommodative coping with self-efficacy, and spirituality. And the spirituality scale had only two bottom questions there which was the least reliable. So then we looked at the correlation between resilience factors and depression, mini mental state examinations for apathy and anxiety. And so resilience scores were oppositely negatively correlated with depression, apathy, and anxiety, which makes sense. If you're resilient, then you're less depressed, less apathetic, or less anxious. In terms of quality of life, resilience highly correlated with emotional health, vitality, mental health, social functioning, and general health. So then we tried to understand what is important for resilience, and we found that depression, apathy, and medical comorbidity undermined resilience, and quality of life, mental health, and general health were correlated with better resilience. Then we explored neurobiological mechanisms of resilience, looking at white matter integrity, which is among the most commonly used imaging abnormalities in geriatric depression. And we aim to determine whether resilience is associated with greater white matter integrity among older adults with major depression. We looked at the cingulum bundle, genu of corpus callosum and anterior limb of internal capsule, and then corticospinal tract was included as a control regimen. And the only correlation that we had with fractional anisotropy, which is a measure of integrity of the white matter, was GREED, GREED factor of this resilience scale. And it correlated highly with fractional anisotropy in cingulum bundle and genu of corpus callosum. And here you could see it in the red on this tract where this positive association between GREED and anisotropy were found. And this is a strength of the correlation in this area scatterplot, identifying these correlations. So this association between GREED with fractional anisotropy in these areas is consistent with prior evidence of the involvement of these regions in emotional regulation and cognitive control, and provides yet another support for understanding of resilience as a complex system comprised of multiple factors, each of which could signify a biomarker or a different pathway for resilience. This is a separate examination of resilience in emotion regulation networks by imaging amygdala nuclei and related brain circuits. So it's a different imaging techniques that looks at the same type of relationship between resilience and brain biomarkers. And we used resting state arterial spin labeling and blood oxygenation level dependent signal on fMRI using called BOLD. And looked at basal lateral, centromedial and superficial nuclei in amygdala, which is rarely done because it's like not even a full amygdala, it's one sort of the amygdala. And found that in depressed individuals and highly depressed individuals, resilience scores are correlated with amygdala function of BOLD signal measured with ASL for all of the centromedial basal lateral superficial nuclei. And when we looked at the relationship between resilience and depression measures, resilience and depression measures correlated with amygdala connectivity using BOLD. Resilience correlated differently from depression with connectivity between the superficial group of amygdala on the left and central default mode network and depression scores were negatively correlated with connectivity between the centromedial group of nuclei on the left and frontal network. So here we described different pathways for resilience and depression, meaning that those are separate processes. You could be depressed but you could also be resilient and I see it a lot in my patients who are quite depressed but they have a lot of strengths and I can devise interventions for them to boost their resilience to counteract depression. Also we analyzed the role of resilience in predicting treatment response in this previously conducted and reported study of 143 older adults with depression who were treated in the metal phenidate augmentation study of Cytella-Pram. And treatment response here was defined as 50% of greater reduction from baseline Hamilton depression score. At 16 weeks, 40% of participants had remitted and 54 had responded. The remission was defined as the Hamilton depression score of six or less. And the only thing out of a whole bunch of factors like the severity of depression, apathy, onset, age, years of education, race, cerebrovascular risk or chronic morbidity, medical morbidity was resilience. Resilience predicted remission. So it's an important factor to boost in order to ensure that remission occurs. So and here only baseline resilience predicted remission as I said and a 20% increase in baseline resilience score was associated with nearly two times greater chance of remission. When we examined individual resilience factors, it was accommodative coping self-efficacy and that refers to ability to adjust to these life circumstances predicted remission. Accommodative coping refers to an individual confidence to his ability or her ability to adapt or accommodate the stress. It is associated generally with more favorable mental health outcomes and consistent with other findings of similar type. So we could devise resilience building interventions focusing on this. And there are quite a few psychotherapy types of interventions like well-being therapy, learned optimism training, hardiness training, all of which focus on positive aspects of difficult experiences. So you turn it into a learning experience. Whatever challenge is, you ask what is the silver lining? What can I learn from it? How can I survive from it? How can I, why is it beneficial for me? And lifestyle factors as you probably know by your own experience is not an easy thing to change in individuals simply because people don't like changes. But it's changeable if you put your mind to it like dietary changes, exercise, spirituality can be enhanced and enhance resilience by creating a better physical and mental well-being. I spent quite a bit of my time experimenting with complementary and integrative medicine using mind-body interventions like yoga, tai chi to create this balance, mind-body balance that would lead to greater resilience. Actually, cardiologists are picking up on that. In the past four years, I've been working with the American Heart Association on different position papers that now implement things like mindfulness and positive and negative psychological factors and find that the worst, most negative thing that can happen to an individual that predicts all worst outcomes of cardiovascular disease like mortality and morbidity, poor recovery from surgeries is being a pessimist. Pessimism is like the worst predictor that leads to worst outcomes, cardiovascular outcomes. However, you could train people in mindfulness or in positive thinking to improve outcomes of even physical illness, cardiovascular disease. In fact, they proceeded with including sleep as a recommendation, a new recommendation for cardiovascular health, recommending seven to nine hours of sleep. And the next frontier is to have recommendations on interventions for stress as an important factor for cardiovascular health. So mindful practices can help achieve mental and physical well-being and health via stress reduction, treatment and prevention of depression in high-risk populations like stress caregivers, older adults with chronic medical conditions and victims of psychological and physical violence. They do have the direct neuroplastic effects in the brain as my studies have shown and others. They also shift consciousness awareness of reality like it's beneficial for me, I can benefit from it, I can learn from it. And also they lead to cultivation of joy, well-being and changes attitude of gratitude which is also has a very significant biological effect on well-being. Mind-body practices can include breath focus, just paying attention to inhale and exhale and following breathing. Mindfulness meditation, deep breaths while staying in the moment can help control obsessions, raising thoughts, anxiety, insomnia. Yoga, tai chi, qigong are ancient arts, Eastern arts from India or China or Japan that use rhythmic breaths with postures and movement also can help distress and enhance flexibility. Prayer is the most commonly used practice, using short prayer for health or enhancing breaths. Guided imagery, pleasant mental images to help relax and enforce positive vision of oneself, control intrusive thoughts. They do have some limitations who could use it, who can subscribe to that. But if people are open to it, those are very important and helpful adjuncts. And it gives patients a sense of control over their own emotions. It's a tool that they can use in their daily life for the rest of their lives. So it's not a medication that get prescribed but that they can control it. So it's important for them to be a participant in this improvement in their well-being. Priorities for mind-body researchers to document effects on self-regulation and emotion regulation, enhancement of physical and mental health, management of pain, depressive and anxiety symptoms, insomnia, PTSD, and other disabilities, and prevention of disease. All of these mind-body therapists and integrative therapists are hitting stress response loops and they work at different areas of the stress response, could be CNS, autonomic nervous system, inflammatory pathways. To start intervening, all of them, mind-body, dietary, physical activity, body-based, natural products, have documented benefit for morbidity, improvement in side effect profile simply because people don't need as many medications. Benefits for cardiometabolic bone and vascular health. And they also can reverse mechanisms of aging, as I mentioned, at different levels. So I study yoga, qigong, and tai chi. They've been used to improve psychological well-being, hypertension, cardiovascular disease, insulin resistance, depression, and anxiety. It's a different type of exercise, unlike aerobic exercise, have a non-competitive, non-judgmental, meditative component, attention on position of the trunk and body and hands or eyes, center breathing, breath awareness, focus on anatomic alignment, and energy-centric, something that we don't measure in Western medicine, but is known to all of us, like life force qi or kundalini prana, SACM, referred to in different practices and cultures. In this article, we compared neural mechanisms of mindful meditation versus movement-based, like yoga or tai chi would be movement-based, and we're more interested in these areas, anterior cingulate, posterior cingulate, prefrontal cortex, and amygdala, and insula, which is a center for self-awareness or interception. And we found that mindfulness-based practices activated four areas, premotor area, mid-cingulate, angular gyrus, primary and secondary somatosensory cortex, and those are areas of motor and emotional integration, somatosensory integration, greater awareness of self-consciousness, can be used for treatment of mood disorders, anxiety, ADHD, impulsivity, movement disorders, and stress. Yoga-based practices activated more areas, and that probably is because yoga uses many more modalities. It's not just attention to the moment, to the breath, or whatever, attentional mechanisms in mindfulness, and yoga involves chanting, it could involve breathing, moving, standing, which is, you know, naturally activates more areas, and those areas of judgment, discernment, memory, language, visual-spatial, somatosensory integration also could be used for enhancing judgment and self-control on deliberate actions. And so, all of it gives us an information how these practices could be useful for enhancing resilience and well-being. This is the study we did of T'ai Chin older adults, the first study a while ago, now published, 112 older adults with major depression, age 60, were recruited and treated first with S-cytallopram, Laxapro, for 10 milligrams for six weeks, and then partial responders were randomized to Tai Chi Cha, which is an abbreviated Tai Chi movement and health education program for two hours per week. The groups did well, both groups did well in terms of depression improvement, but Tai Chi group demonstrated significantly greater improvement in resilience, energy, psychomotor retardation, physical functioning, cognitive measures of executive and cognitive function, and attention. Here's the response on Hamilton depression score of 10 or less. Tai Chi had almost 95% responders. Health education didn't do too badly either, a 75% response. And here we have response in depression levels in parallel. But when it gets to the physical functioning, the groups diverge in how they respond. Also, memory tests showed divergence with health education declining and Tai Chi group improving on memory. And then inflammation also declined in the Tai Chi group. This is the more recent study of a larger sample that looked at brain connectivity and what we found that Tai Chi really stimulated brain connectivity in various areas of the brain in multiple nodes, and that improvement in connectivity is also related to improvement in depression and resilience. Also, on this test, it tests individual's reaction to negative stimuli, in this case, negative faces. And it showed how Tai Chi, why Tai Chi reduces brain response to emotional faces by decreasing activation in this area of the brain here in blue, that in right fusiform gyrus, that signifies a reduction to stimuli, negative stimuli, so people don't react, become less reactive with these practices. In both groups, however, remitters showed improvement in inflammation in this various inflammatory factors that we derived from a panel of 39 cytokines, peripheral cytokines, and non-remitters in both groups did the worst, so they had more inflammation at baseline. So that combination of studies showed that complementary use of mind-body exercise combined with standard antidepressants can provide additional improvement in clinical outcomes, improve resilience and quality of life, cognitive function, via stress reduction, decreased inflammation, epigenetic changes, improved emotional regulation, direct anti-inflammatory neuroplastic effect, and could be recommended for those who are open to this intervention. So I'd like to thank sponsors and collaborators, especially National Center for Complementary and Integrative Health that sponsored the studies, all of my collaborators. Thank you. And. Thank you. Any quick questions for me? No? We'll go to this last talk by Dr. Dilip Jesti, who needs no introduction. You all know him as a past president of the EPA or American Association for Geriatric Psychiatry. Okay. All right. Good afternoon, and thank you, Helen, for inviting me here. So I'm going to talk on overall resilience and well-being in older adults. No relevant conflicts of interest. I'm going to begin with what is healthy aging? Next is the psychosocial determinants of healthy aging. And finally, intervention and prevention strategies. So what is healthy aging? If you use the word, actually, if you look at the word aging in any dictionary, the definition of aging is almost always associated with some deterioration, decline, and all of the bad things that are there. And yet, there are people who do very well in older age. This is Ida Keeling. This was a story that came out in New York Times a few years ago. And you can Google Ida Keeling and you'll get a lot of information. So this was a lady in New York City who functioned well. And in her 70s, she started getting somewhat depressed. She had stopped working. And her daughter said, why is this happening? You know, let us be active. Let us go together, take some walks. And after that, so she really got into physical activity. At the age of 100, she set a world record for centenarians in 100-meter dash. Wow, right? so of course we would say that that's healthy ageing because she's physically so healthy, right, at 100 she can do this 100 metre dash. What about people who are disabled, somebody in a wheelchair, being in a wheelchair means disability, an older person in a wheelchair cannot be ageing successfully, right, that's the usual definition. Some of you will know this person, FDR, President Franklin Roosevelt, he was the president during the Second World War, he served as the president for 12 years, the longest serving president in the US history. He developed polio in his early 30s, that was followed by Guillain-Barre syndrome that left him paralysed in both legs and he was in a wheelchair for all of his adult life. At that time there was no TV or video so most people didn't know that he was in a wheelchair. So is that an example of unsuccessful, unhealthy ageing because he was in a wheelchair? Of course not, right, I mean he was one of the most successful leaders in the world of all times in spite of being in a wheelchair. So that means that healthy ageing is not just physical health, it is something different. So we did a study some time back of physical health and mental well-being, a study in 1500 San Diegans and this was somewhat randomly selected population, we used random digitising, this is what the Gallup poll does, random digitising, right. So this was not a sample of convenience, a sample of healthy people, nothing like that. So we measured their physical health and mental well-being and physical health, so this is what you see, in the 20s and 30s it is at the best and then it starts declining, this is exactly what we expect with ageing, right, 20s and 30s there is fountain of youth, perfect physical health, by the time we reach 90s most of the people will be disabled. What about mental well-being? It goes exactly in the opposite direction. So the fountain of youth is also a fountain of depression, anxiety and stress and many of us will, if we look back at the time we were in our early 20s, that's a pretty tough period, you know, we had to make major life-changing decisions, what education to take, continue, take up a job, which job, where do we settle, choosing a life partner and we often feel that we are not doing as well as our peers. The things have gotten worse in the last couple of decades because of the social media and the higher pressure, younger people are doing much worse today than they were doing 30 years ago, the rates of suicide have gone up in younger people. So the fountain of youth is actually not fountain of health from the mental health perspective. The good news for ageing is that as we get older the mental health improves, mental well-being improves. The stresses don't go down with ageing, they never go down with anything, but the way we cope with stresses improves and that's what causes decrease in stress level and increase in well-being with ageing. So what is age then? You know, there is a multi-billion dollar anti-ageing industry, you can spend lots of money on getting the supplements and various magnets and various kinds of therapies that will prevent ageing, that means ageing is something bad, it's like cancer, we want to avoid it, prevent it, right, or cure it, well, that's not true. As Helen mentioned, ageing is something, the process begins at conception, ageing doesn't start at 65, it begins at conception, so even an embryo, one day old versus two day old and clearly one year old baby versus two year old baby, different. More importantly, the idea that ageing is only deterioration and decline is wrong. Typically we think about childhood as a period of growth and development and old age is decline and degeneration, that's not true. Ageing is an active and ongoing life process that begins at conception and is associated with a dynamic balance between growth and development on one side, degeneration on the other hand. There is degeneration in childhood, for example, the number of synapses and neurons declines with ageing. On the other hand, brain can continue to develop and I will talk about that shortly, new synapses and even new neurons in some regions of the brain if the person stays active. And this is a very nice report that came out from the National Academies of Sciences, Engineering and Medicine called Whole Health, Achieving Whole Health, and they define whole health as physical, behavioral, spiritual and socioeconomic well-being as defined by the individual's families and communities. I really think this is going to be the definition of health in future because it's coming out of the National Academies and it will have a large influence. So think about this, it is not just physical health, it is also behavioral, spiritual and socioeconomic. So the things I talked about, ageing and well-being with age, that also applies to people with mental illnesses. We usually think about mental illnesses as nothing but psychopathology. That's not entirely true. A sizable minority of the patients with serious mental illnesses have well-being scores in the normal range and their well-being correlates not with physical health, not with even psychopathology, but with levels of resilience, optimism and other positive traits. Remission or recovery in schizophrenia is not an oxymoron. Some people call schizophrenia cancer of the mind and it's a life sentence. So the idea is that there is no cure, nothing will happen. Not true. I will talk about that shortly. And the most important predictor of recovery or remission in schizophrenia is not biological, it is social support. And an example, and some of you are probably familiar with this, is Beautiful Mind. This is a true story, by the way, if you haven't seen the movie, please do that, it got the Oscar for the best picture in 2001. Actually based on John Nash, who got Nobel Prize in economics some years ago, he, obviously he was a brilliant kid, teenager, he developed a game theory. But he also was diagnosed with schizophrenia in his early 20s and for the next 30 years he was in and out of hospital, got ECT, insulin coma, all kinds of medications, psychotherapy, everything you name it. Not much change. At age 50 he started eating better. Symptoms started going down. At age 60 he went back to research, he published a paper for the first time after 30 years. And at age 66 he got the Nobel Prize, not for the newly done research he had done back in his 20s, but still. And he was a keynote speaker at the APA about 12 years ago. Even with schizophrenia, being a keynote speaker at the age of 70, isn't that amazing? So what are the psychosocial determinants of healthy aging? Social engagement, resilience and optimism, and of course you heard about resilience. Social engagement is probably the single most important determinant of health and longevity. Meta-analysis has shown that social connections have greater impact on health and longevity than all the medical risk factors we think about, hypertension, diabetes, smoking and various other conditions. A series of 148 studies, including a sample of greater than 300,000 people from across the world, showed there is a 50% increased likelihood of survival among socially engaged people compared to non-socially engaged people. Wow, 50%. And resilience, as you heard from Helen, clearly a lot of clinical data showing that resilience is associated with better health. Optimism also, as again Helen mentioned, so this meta-analysis found that optimism was associated with better cardiovascular outcomes, physiological markers like immune function, cancer outcomes and mortality, all P is less than 001. And many of these studies control for the thing that we want to control for, past history, family history, use of statins, smoking. So this is where really many of them were very well done studies. Still found that optimism is a major predictor of improved functioning and health and longevity. One thing that I've been personally interested in for the last dozen years or so is wisdom. Wisdom is an ancient concept in all religions and philosophies, but for the last 15 years there has been growing empirical research on wisdom. And the wisdom components include things like emotional regulation, positivity, empathy and compassion, self-reflection, decisiveness. Number of studies across the world have shown that if you compare younger people and older people, the younger people do better in several ways. They have much more, much faster psychomotor speed. They can learn new things much faster than older people. On the other hand, older people do better on several things. They have more emotional regulation. Again, think about a teenager versus an older person. I think you can see the difference in emotional regulation clearly, right? Positivity, favoring positive emotions and memory, empathy, compassion, self-reflection, experience-based decision-making because aging comes with experience, right? So these are the components of wisdom and studies show that older people exhibit higher level of this component than younger one. Of course, this doesn't apply to everybody. There are some very wise young people and some very unwise old people. No question about that. But by and large, older people tend to be wiser than younger ones. Now, thinking about that at a larger level, community level, unfortunately there are very few studies of things like resilience, optimism, and so on at the community level. But there is some work on family resilience and we know there are families in which people are resilient and other families in which they are not. So there are three dynamic structural features of the family system. One is family belief systems that facilitate overcoming a crisis via positivity and meaning making. So you see when there is some major crisis disaster, some families do pretty well because of the belief system. Another is organizational patterns during a crisis. The family has an organized structure and they use that for helping especially the younger ones. And communication processes with open emotional expression and collaborative problem solving. So when there is some crisis that affects an individual in a family, the whole family comes together and they can solve the problem. And so those individuals in crisis actually do much better in those families than in others. Post-traumatic growth. You know, we all know about PTSD, post-traumatic stress disorder, which is very common, right? But trauma is not always followed by PTSD. There are people and communities in which there is what is called post-traumatic growth. So it reflects positive changes that people experience following a struggle with an adversarial event. And that adversarial event can be a natural disaster like terrorist crisis, you know, or it can be personal. And there is a 21 item post-traumatic growth inventory that has been developed. It has five factors. Greater appreciation for life, improved relationship with others, greater personal strengths, new life possibilities, and spiritual existential growth. So instead of responding to stress with depression, stress, anxiety, you respond with positive things like greater appreciation, more social connections, improved relationship with others, and so on. And actually, I did a quick literature Google review of post-traumatic growth examples. And really, I was fascinated by the papers I saw. One paper is on three generations of Sikh and Slovak Holocaust survivors. Another one was on 2011 Oslo bombing attack, then, of course, the 9-11 World Trade Center exposure 15 years after 9-11, natural disasters in children and adolescents, and finally, after a prolonged war, a study in Baghdad, Iraq. So all of this crisis, wars, some short-lasting, some long-lasting, created major problems. But there were families and communities that came out of this in a positive fashion. So we have to keep in mind that there are positive things that happen after stresses. So talking about COVID-19, I mean, that was really a major crisis. So when COVID-19 started in 2020, early part of 2020 in the U.S., the initial reports were all about deaths in nursing homes. And it was clear that older people were more vulnerable to physical complications and deaths. Then the social isolation to stop the spread of the pandemic, that created problems because then you couldn't really have social relationship in person, right? The younger people did very well because younger people had, you know, for one thing, physically they were healthy, they didn't have complications, and they had all access to technology, FaceTime, social media, iPhone, and what have you. Older people didn't have that. So the expectation was that older people are going to be much more depressed, anxious, and stressed out with COVID than younger people. You know what the data showed? Exact opposite. It showed that the prevalence of psychopathology, that is depression, stress, anxiety, was lower in older people and that higher resilience. And this was one specific study done in the U.S., 5,000 plus U.S. adults. The prevalence of psychopathology, and by psychopathology, I mean, again, depression, anxiety, stress, and so on, was 15% in adults over 65 compared to 75% in adults age 18 to 24. So these younger people were physically fully healthy, they had access to all technology, and so they could connect with, communicate with one another very easily. They didn't do well at all. Why? Because there were, instead of post-traumatic growth, there was post-traumatic stress disorder. Older people often said that, you know, yes, COVID is terrible, but we have been through crisis like that before. They have been through droughts, wars, economic depressions. Whereas for younger people, this is the first time they faced a crisis. They didn't know how to handle it. So what it means is that old age is not all bad, but actually you can have greater resilience and you do better than the younger folks. Lastly, intervention prevention strategies. So I think in our current practice, we really don't ask for the thing that really affects health and longevity. For example, I talked about social connections being so important to health. So there is something called social network schedule. Similarly, there is a scale for measuring resilience. Again, Helen talked about that Conor Davidson Resilience Scale. Wisdom, we developed a scale called San Diego Wisdom Scale. On the other hand, on the negative side, there is a scale for loneliness, scale for childhood trauma, and experience of discrimination. Discrimination of different kinds, including racism. So these are factors, social factors, and psychological factors that have a major impact on health and longevity. Greater impact than the medical risk factors, and yet we don't assess them or do something with them. And that, I think, needs to change. So when we see a person with schizophrenia, typically what we do, we prescribe antipsychotics and we prescribe supportive therapy. And that's great. I mean, we need to do that, but that's not enough. What we should be doing is, we should also prescribe cognitive behavior therapy, social skills training, physical activity, physical exercise, running, walking, socialization, meaningful socialization. That's important, especially for people with schizophrenia who can be stressed out with wrong socialization, right? Healthy diet. Healthy diet does not have to be expensive. There are ways in which inexpensive healthy diet can be obtained. Sleep hygiene, job or volunteering, and positive attitude. That's something so important. And that, so again, thinking about schizophrenia as a cancer, it's something that's wrong. Look at John Nash and several other examples. We should have positive attitude toward that too as clinicians. So intergenerational activities help both generations. Numerous studies have shown that if you Google this experience score, you'll find more about it. It's a great study that was done about 20 years ago, supported by MacArthur Foundation. What they did was, they took older people who had retired from their jobs and they randomized them into two groups. One group was asked to go and spend at least 15 hours a week to help kids in public elementary school, okay? So they had to go there and help them with their math, et cetera, and just crisis, you know, life situation overall. After one year, these kids did of course great. They were very happy. Their grades went through the roof. Older people did very well too. Their physical health improved, mental health improved. Their biomarkers of aging and stress improved in blood and urine. And the volume of the hippocampus was larger on brain MR at the end of the study in these people compared to the control. Not that the hippocampus grew in size, no. It means that it did not shrink the way it did in the people who did not have those activities. I'm coming to an end. So how can we do this at the community level? Some great examples. One is Compassionate Community Movement. Started in New Zealand, now in Europe, hopefully will come to U.S. So what they do is the government, local governments, businesses, academics, other agencies come together. They form groups of volunteers, health and social care supports, and they try to help the most vulnerable people, most disenfranchised people in the community. Very well done study in Canada. The qualitative study found that this program acted as a safety net that supported people from falling through the cracks of the formal care system. And there were three key processes, taking time, advocating for services and resources for these people, and empowering clients to set personal health goals and make the community connections. Another great example of this is the Age-Friendly Community. The WHO started this about 20, 25 years ago. So these are the communities which involve, again, collaboration between government, businesses, academics, and community focusing on healthcare, lifestyle, technology, and intergenerational and voluntary activities. So it includes improved housing stability, transportation, outdoor spaces, respect and social inclusion of older adults, civic participation, employment, communication, information, health and wellness services. We should do these things not out of compassion for older people. We should do these things because they're helpful for the younger generation. And if older people stay active by helping younger people, the older people will stay healthier. The healthcare costs will go down. So it is in the interest of the society to promote intergenerational activities increasingly. Thank you for your attention and all. Thank you. So we could have a discussion. Thank you so much. What was the topic? Oh, it's something. It's something. Any questions or remarks? Hey, Barbara. This was really fabulous. I mean, it's an innovative paradigm to change the way we think as physicians about medicine, which is always the pathology of organs. One thing I was wondering was whether or not insight is a factor to resilience. So that if somebody has insight into the fact that they have, let's say, schizophrenia, they're likely to take their medications more, not drink, and so on. Is one a proxy for the other? Let me answer and then talk more about it. I think that is definitely the case. Insight is important. And even outside schizophrenia, I mean, if you talk about wisdom, one of the components is self-reflection, understanding yourself. Clearly, everybody needs to have understanding of their own strength and limitation, because then one is able to handle the crisis much better. So absolutely, your point is well taken. And so that should be an important component of psychotherapy, instilling and helping the person get insight. I'm frequently interviewed by all sorts of media about what I think is a core for the epidemic of mental health problems, especially among younger people. And I do integrative psychiatry in addition to being in geriatric psychiatry. So through my work with the American Heart Association, the key to overall response and improvement in mental health is insight, or what I call awareness, raising awareness about their bodies, mind-body connection, how to self-regulate. So awareness is the key component of self-regulation, because you can self-regulate being unaware. And in this Western society, because of the success-oriented philosophy of life, we live above neck, I call it. There's no complete disconnect. If you go to a gym and you look at who's exercising and how, mostly they're on those machines watching something else or being on their phones or whatever, which precludes from being connected, mind-body connection, full awareness of mind-body function. And the rebalancing of the body comes from this balance between mind and body, because we live above neck and our mind commands to our bodies. For example, women tend to overdo stuff. I'm sorry to men in the audience. They're professional caregivers and they deny their own needs most often. That's how we're programmed to be in this society. And until they reach menopause. And after that, they fall over because estrogens are a gun and they're protection against this negative effect of chronic stress, chronic caregiving, overdoing. And they find their body at that point, but the body is broken. And so the reconstitution of the body comes from this awareness. So insight is a core to change. Do mice have insight? Yeah, this actually is something we have been struggling and debating among the community. So, yeah, what is the aspect that is accessible in non-human animal model and what is not doable, especially when we talk about emotional well-being, which is a complicated function. So at this point, we don't think we are starting in very higher level function or this kind of more reflective or evaluative components in non-human animals. And we will probably only rely on animal to study more like a behavior or experience aspect. Okay. That was a meaningful discussion, I would say. Any other questions or comments? Hi, excellent, excellent. In the paradox of aging, you know, we increase the physical health and grow the mental well-being. In which percentage, you know, how many people grow in well-being with age and how many people know not? And am I clear? How many people? Achieve well-being? Yeah, you know. Oh, what are you looking at? Not all the people. What are you looking at? Oh, okay. Oh, that was based on the rating scale that we used. So the rating scale that we used was SF-36, the short form 36, which is probably the most commonly used scale for well-being. It has two components, physical component and mental component. So it's not subjective. So these are questions you ask about energy, vitality, they feel, but also about stress level and so on. So it's a reasonably valid summation of both physical well-being and mental well-being. And so that's what we had done. And so the physical well-being going down is of course as expected, the mental well-being going up. But also if you think about that, that's actually what happens. Many of us above a certain age, if you look back as what things have happened to our well-being level, you'll find that older people, an 80 year old person in a wheelchair is often happier than a 20 year old who is fully healthy and yet severely stressed out. And I think it is important to realize that physical and mental well-being are different. And ultimately what happens to the person is mental well-being. Can I, yeah, just to add, so in terms of the mental well-being, so usually we also try to decompose it into the cognitive and the emotional domain. And then there is a kind of very famous perspective from Martha Mara on emotional paradox. So which is cognitive, typically cognitively is declined, especially for the higher order of cognitive function like memory, the executive function. However, emotional well-being or emotional function actually increase over time. And we may see this kind of U-shape, meaning in the middle age, and there may be middle age crisis, but in older age, it rebound and actually improve a lot. So this kind of paradox between the cognitive and the emotional domains in older age is something I think a lot of neuroscientists are very interested in studying. So I became aware of the children's study of environmental toxicities recently through their presentation at NIH. And it's a massive effort to understand the role of environmental toxicities and factors on mental health and physical health. And what was surprising to me, we know that children are resilient, but children who are burdened by chronic illnesses and severe illnesses like cancer or kidney insufficiency and failure had almost as much resilience as healthy children. That just tells you that you really have to look at resilience as a feature that could be built up. And I was recently asked by a reporter about why we're experiencing such stress, anxiety, and depression, and really epidemic among younger adults. And that is because they don't have tools to self-regulation and coping mechanisms. And they're devoid, they're basically bombarded by negative information either through social media or environmental stresses of any sort. And the resilience is not being trained or taught in schools. And my solution to this crisis is actually to start interventions as early as possible. I have one question. Thank you so much, that was illuminating in so many ways. I had a question for you about arts organizations. And I know the Metropolitan Museum had done a collaboration with City Meals on Wheels that delivers food to homebound elderly New Yorkers. And so what they decided to do was to actually create, put an art box inside the deliveries once a month, and then ask people who are recipients of these meals to talk to their volunteer about, there were prompts in the art box about what was meaningful or interesting, and they gave them tools to use, and pencils, and paper to draw on inspiration, sort of postcards and things like that. And they also gave them passes so that they could maybe give a neighbor free passes to go to the museum if they wanted to. So the idea was to create, sort of make them givers, not just receivers. But what it seemed that the art box did most effectively was created good conversations between the meal recipients and their healthy volunteers. What would you recommend would be the best measure of the benefits of that impact? And if you can't sort of measure it, it doesn't matter in a way, what would be the best way to measure the impact, the benefits of that? Yeah, it's perceived stress, which would be a negative, and the quality of life would be the positive. And you could measure resilience with short, brief measures, like two, three questions, or 10 questions. But those would show the shift in perceiving their situation. You know, and also measures of social support, because this kind of intervention really, for lonely older adults or lonely people would really increase social support. Also, cognition. So if you're targeting aging community, I think the cognition overall probably will be a very important aspect. And also, there has been actually recent emphasis from NIH for studying different art-type therapies for enhancing cognitive capacity in older adults. And actually, so I'm actually, myself, is an instructor for art class myself, and teaching painting and clay-related work. And it's actually helpful, not just in the brain function, but also like a lot of this kind of subtle mobility type, this kind of button-up inference in the brain. We actually studied exposure to digital art versus nature videos, and meditation experiences. And art has a very unique neuroplastic effect on the brain. We're also waiting for a funding decision on music, brain, and prevention of dementia, brain health and the prevention of dementia network. So yes, and NCCIH, National Center for Complementary Integrative Health, and NIA, National Institute on Aging, are both interested in art-based intervention. Yes. Actually, also, we should talk about well-being in the volunteers who are helping. I think, because increasingly, I think the focus in the healthcare is also on the whole healthcare team's health, and encouraging people to volunteer because they get a purpose in life, and meaning to what they are doing. And so their well-being improves. And if they are happier, then that happiness will be also conveyed through the recipients. And so I think that that's, and that's where, again, intergenerational activities are an example of that, where both are help, recipients as well as the deliverers of the care. The creative component, creative creativity is a dopamine-generating activity. You know, you get pleasure from being creative. And especially in older adults who have limited mobility, something like painting or drawing or creating music. I'm working with the organization called Music Mends Minds, and it's in Los Angeles. They became global over COVID because they had sing-along choir for people with Alzheimer's disease, and orchestras, even on Zoom, of people, musicians with Alzheimer's disease. And it's really remarkable just to look at the videos. They also have drumming circles that go to assisted livings and senior centers, to the point that Los Angeles County decided to hire them to develop a program county-wide to go to all senior centers to create these programs. Any other questions or reflections? I think we're out of time anyway. Thank you so much for staying and participating. Thank you.

brain aging

resilience

emotional well-being

cognitive resilience

older adults

neuronal resilience

mind-body interventions

yoga

Tai Chi

social engagement

emotional regulation

integrative health care

intergenerational cooperation