Geroprotective and senoremediative strategies to reduce the comorbidity, infection rates, severity, and lethality in gerophilic and gerolavic infections

By: Alex Zhavoronkov

In: Aging

Date: 31 March, 2020


  • COVID-19 disproportionately harms the elderly.
    • Infection rates, severity, and lethality all increase with age.
    • Mostly because of higher levels of comorbidity among elderly.
  • May also be due to decreased immune function.
    • Immune system deteriorates with age.
  • Decreased immune function may make vaccines and treatments less effective for elderly.
  • Strategies to boost immunity may help decrease infection rates.
    • Rapamycin, NAD boosters, and others.
    • Need more research.
  • Highlights the need to understand biological aging to better protect elderly population.
    • To help assess the need for geroprotective interventions.

COVID-19 is a gerolavic, disproportionately affecting the elderly.

  • Gerophilic versus gerolavic:
    • Gerophilic: pathogens that are more infectious and prevalent in the elderly.
    • Gerolavic: infections that are more widespread but disproportionately affect the elderly.
  • COVID-19 = gerolavic.
    • Statistics indicate that infectivity, severity and lethatility of COVID-19 are age-related.
    • Increase in age -> increase is infections, severity and fatalities.
  • COVID-19 accelerates and compresses fatalities.
    • May not be the only cause of fatality.
    • Difficult to disentangle from comorbidity, lifestyle, etc.

Immune system deteriorates with age, driving higher infections, severity and outcomes.

  • Immunosenescence:
    • Gradual deterioration of immune system with age.
  • Driven by thymic involution.
    • The thymus is a specialized lymphoid organ of the immune system.
      • Positioned in front of the heart, behind the sternum.
    • Within the thymus, T cells mature.
      • T cells are critical to the adaptive immune system (adapt to foreign invaders).
    • Most active in fetal and neonatal life.
      • Continues to grow after birth reaching the relative maximum size by puberty.
      • By early teens, thymus begins to decrease in size and activity (involution).
    • Thymus is gradually replaced by adipose tissue (fat).
      • Atrophy of thymus is due to the increased circulating level of sex hormones.
    • T cells exiting the thymus decrease significantly with age.
  • Because of this, elderly have reduced ability to resist infection.
    • Infection produces biological damage and loss of homeostasis.
    • Accelerated aging and the development of age-related diseases.
    • Increase in multi-morbidity.

Classic treatments for infectious diseases: vaccines and anti-virals.

  • Vaccines.
    • May be the best preventative strategy.
    • Reduce infection rates, severity, and lethality of COVID-19.
    • Success of a vaccine partly depends on similarity of vaccine strain with viral pathogenic strain.
    • For example, influenza, vaccination based on predictions of strain variants.
  • Antivirals.
    • Prophylactic treatment prior to symptom onset in high-risk groups or after exposure to virus.
    • Alternative preventative strategy against viral disease.
    • For example, for influenza, the neuraminidase inhibitors oseltamivir and zanamivir.
    • Reduce symptom duration, and reduce complications and transmission risk.
    • Greatest benefit when drugs are administered 24-30 hours prior to symptom onset.

Success of vaccines may be lower in elderly.

  • Individual’s immune response must be sufficiently strong.
    • First, mount a reaction to the vaccine.
    • Later, confer protection against the pathogen, should exposure occur.
  • Vaccines do not provide complete protection in older populations.
    • Due to age-related declines in immune function and accumulation of multi-morbidities.
    • Outbreaks can occur in elderly nursing homes even with vaccination rates at 80-98%.

Need to improve immune system to reduce infection risk, symptom severity, or improve vaccine efficacy.

  • Even with successful vaccine for SARS-CoV-2, will need something to boost immune response.
  • Strategies to improve immune system in the elderly.
    • Rapamycin and rapalogs.
      • Immunosuppressant, but may boosts T cell responses in reaction to pathogen infection and vaccination.
      • Also, morbidity from coronavirus infections may occur from secondary overactive immune responses.
    • Metformin.
      • Lowers blood sugar.
    • NAD boosters.
      • May enhance DNA repair.
    • Others.
      • Senolytics, stem cell treatment.
  • To be used in isolation or combination with other therapies.
  • Lack of clinical evidence to support their immediate use.

Biological age is more important than chronological age.

  • A person’s chronological age is not as important as their biological age.
    • Need to develop accurate aging biomarkers.


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