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