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Lecture on Demographic Trends, Variability, and Malleability of Aging
Jul 28, 2024
Lecture on Demographic Trends, Variability, and Malleability of Aging
Introduction
Focus on demographic trends and aging
Variability and malleability of aging
Immune aging and modern lifestyles
Features of immune aging
Importance of an institute focusing on inflammation and aging
Demographic Changes
Birth rates are falling, particularly among under 16s
Over 65s and 85s are increasing in number
Predictions by 2034: Nearly 25% of the population over 65 and 5% over 85
Longevity and life expectancy are highly variable, even within cities (e.g., Birmingham)
Variable Experiences of Old Age
Examples of variable experiences of aging: Actresses Sofia Loren, Brigitte Bardot, Elizabeth Taylor
Female life expectancy has increased but healthspan lags
Increasing frailty with time
Tackling Age-Related Diseases
Most chronic diseases are age-related
Current paradigm: Tackling diseases individually (e.g., cancer, cardiovascular disease)
Proposal: Tackling the aging process itself
Caloric Restriction & Longevity
Reduces calorie intake by 25-30%
Increases lifespan in species (e.g., C. elegans, macaques)
Reduced age-related diseases in calorically restricted animals
Epidemiological hints: Okinawan longevity and health indicators
Immune System Aging
Roles: Detect/kill pathogens, remove damaged/cancer cells, immune memory, self-protection
Evidence of immune aging:
Increased bacterial infections (e.g., C. difficile, MRSA)
Declining vaccine efficacy (e.g., tetanus)
Shingles and immune memory fade
Age-related cancers (e.g., AML)
Autoimmune diseases (e.g., rheumatoid arthritis)
Mechanisms of Immune Aging
Decline in naive T cells, increase in senescent T cells
Problematic telomere shortening in lymphocytes
Changes in T cell receptor signaling and autoimmune risk
Neutrophil function declines: reduced phagocytosis, ROS generation, extracellular killing
Increased vulnerability to infections and higher systemic inflammation (inflam-aging)
Impact of Lifestyle on Aging
Compared to 150 years ago, longevity has increased due to modern lifestyles
Varied impacts of sedentary lifestyles and food availability
Sedentary behavior prevalent in over 65s (esp. females)
Benefits of Lifelong Physical Activity
Study on cyclists aged 55-79: maintained muscle mass, metabolic health, and thymic output
Reduced age-specific declines in immune markers
Lessened systemic inflammation
Results suggest active lifestyle mitigates some aging effects
Interventions and Future Directions
Exercise as an adjuvant in enhancing vaccine efficacy
Caloric restriction mimetics: e.g., Rapalogs to improve immune functions
Use of adjuvants like flagellin in vaccines for better response
Timing interventions (circadian biology) to improve immune responses
Pharmacological approaches to correct immune cell defects (e.g., PI3 kinase inhibitors)
Personal Reflections on Career
Unplanned but impactful progression
Importance of mentorship and goal-setting
Value in national and international visibility, fellowships, and reviewing roles
Translational research in close proximity to clinical settings (e.g., Queen Elizabeth Hospital)
Balancing career with personal interests and activities
Engaging in political campaigns to support science
Emphasized teamwork in research spanning basic science and clinical applications
Conclusion
Lifelong physical activity and certain medical interventions can improve immunity and general health in old age
Teamwork among diverse roles (basic scientists and clinicians) crucial for impactful research
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