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