By: Alex Zhavoronkov
In: Aging
Date: 31 March, 2020
Summary
- 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.
- The thymus is a specialized lymphoid organ of the immune system.
- 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.
- Rapamycin and rapalogs.
- 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.