How Aging Science Will Help Us Fight Future Pandemics

A scientist’s view on COVID-19 vulnerability,
preparedness, and hope for the future

As the world responds to the COVID-19 pandemic, scientists across the globe are working tirelessly to understand the complexity of the disease. We talked with longevity scientist, Alessandra Zonari, PhD, to better understand the connection between infection vulnerability, aging, and COVID-19.

Alessandra
Zonari, PhD

05.27.20

01Q: What have scientists learned thus far about populations most at risk for contracting COVID-19?

A: One of the first lessons from studying the ramifications of COVID-19 is that the infection disproportionately affects the elderly. Globally, over 80% of COVID-19 hospitalizations are patients over 65 years of age. For those who are over 80 years old, the chances of death resulting from confirmed COVID-19 infection are increased to 21.9%.

“Beyond working on combating the COVID-19 virus, we need to strengthen our own bodies, as we are the ‘hosts’ of the virus.”

As scientists, we ask ourselves what these numbers really mean about the infection. And what we’re learning is that aging poses a remarkable risk to the evolution of the COVID-19 infection. More profoundly, the data signals to us that if we fight aging, we can do more in our response to the disease. Aging has long been considered a risk factor of many diseases, but likely, aging is a disease in and of itself that can be treated. Beyond working on combating the COVID-19 virus, we need to strengthen our own bodies, as we are the ‘hosts’ of the virus.

02Q: What can contribute to greater risk for developing a more severe prognosis of COVID-19?

A: Several aspects of aging are correlated to the increased number of elders contracting COVID-19. When a person ages, the overall level of inflammation in the body accumulates and contributes to a biological process known as inflammaging. What this means for a virus like SARS-CoV-2 (the strain of coronavirus that causes COVID-19) is that with higher levels of inflammation, the amount of ACE2 (a molecule that binds to SARS-CoV-2 virus) on the cell surface increases, which makes it easier for the virus to enter our cells and replicate. Furthermore, with age, the number of immune cells that are responsible for killing virus-infected cells present in the body are reduced, reducing the body’s innate defense mechanism to combat the infection. Therefore, increased inflammation can result in a worse prognosis of the disease.

Strengthening the immune system’s ability to fight an infection faster will not only help the body’s biological response to SARS-COV-2, but also prepare the body to respond to a wide range of diseases and new infections.

03Q: Reports say that it could take over a year to develop a vaccine. What other therapies could help fight the virus in the meantime?

A: As we find ourselves in this unique waiting period for a vaccine to reach approval and thoroughly undergo clinical trials, the current goal in the scientific community is to find new treatments, such as an antiviral drug specific to the virus.

“...if the human body is better equipped to function at a more optimal level, it will respond better to future viral infections, including the one responsible for COVID-19.”

There’s a lesser known therapy being investigated that is definitely worthy of an explanation, and it’s the use of geroprotectors. Geroprotectors are a class of drugs designed to fight one or more hallmarks of aging with the goal to improve a person’s healthspan (the period of one’s life free from disease) and/or increase lifespan. Research in numerous model organisms have previously shown that many of these drugs such as metformin, rapamycin, and senolytics can reduce inflammation in the body, prolong animal health, and delay the development of chronic diseases. The idea here is that if the human body is better equipped to function at a more optimal level, it will respond better to future viral infections, including the one responsible for COVID-19.

04Q: Are geroprotectors already being tested in humans?

A: Yes, in clinical trials. What is especially interesting is that at the moment, researchers are trying to correlate the use of these drugs with the recovery rate of COVID-19.

Metformin, a widely used drug for treatment of type 2 diabetes, also displays promising data for protection from aging-related diseases through metabolic and inflammatory pathways. Several clinical studies show that type 2 diabetics that take metformin have lower rates of dementia, cardiovascular disease, cancer and frailty compared to patients that don’t take metformin, even if those individuals are not diabetic. Researchers are now mapping the outcome of patients treated with metformin who recovered from COVID-19 to understand if the drug had protective effects.

Another interesting finding came from a phase 2 clinical trial of a geroprotector (RTB101) in patients with Parkinson's Disease. The data showed that individuals taking the drug had a reduced incidence of respiratory tract infections caused by multiple viruses including coronavirus (tested with other strains, before SARS-COV-2) compared to a placebo.

Although these findings are still in preliminary phases, this data gives us one more clue that drugs designed to target the biology of aging can strengthen the host's health to fight against infectious diseases.

05Q: While we wait for scientifically proven data on the safety and efficacy of geroprotectors, what can I do to prepare my body for a potential viral infection?

A: Simple behaviors such as exercising and following a healthy diet will naturally help reduce the levels of inflammation in your body. Here’s why: the skeletal muscle is a key immune regulator. When this muscle is activated through exercise, it releases molecules called myokines which change the profile of immune cells to an anti-inflammatory state, increases the number of cells from our immune system responsible for killing infected cells present in the body, and modulates fat cells (also responsible for inflammatory molecule release).

A recent study compared inflammation levels in the blood of older adults (55-79 years) that maintained a high level of physical activity (cycling 100-150 kilometers/week) with sedentary individuals including both young adults and older adults. The result was impressive and determined that levels of inflammation in the blood for those older adults that engaged in regular exercise was similar to the levels found in the young adults.

For those that aren’t as keen on exercising so vigorously, another study involving 200 people over the age of 65 demonstrated that increasing one’s daily step count to over 10,000 steps per day decreased inflammation levels in blood.

Nutrition is another way to maintain a strong immune system. A healthy gut microbiome, a diet rich in fruit and vegetables, Vitamin D, Zinc, and low in sugar have shown to influence the immune system, including reduced levels of inflammation.

06How do you see research on aging and longevity impacting society?

A: I’m personally very excited about what’s to come in the next few years. There has been a huge uptick in the number of researchers, institutes, biotech startups, and funding in the longevity field. There is no more logical way to fight disease and infection than through prevention. In hindsight, this couldn’t be more clear to the general public - all the newly instituted COVID-19 restrictions and stay-at-home orders have made us realize that our health is our most precious asset.

“Longevity research has shown that lifestyle behaviors and therapeutic interventions are able to delay the aging process in humans to increase the healthy years of life.”

Longevity research has shown that lifestyle behaviors and therapeutic interventions are able to delay the aging process in humans to increase the healthy years of life. Aging doesn’t need to be a burden as it’s unfortunately so commonly experienced today. Aging can be treatable. Strengthening our immune biology will better equip our bodies to fight future diseases, and this will not only influence the quality of your own life, but have a significant impact on society and economy.

It’s never too late to incorporate healthy habits no matter what your age is. Over the past two years, I changed some of my own habits including daily exercise, meditation, fasting, and a healthier diet, and I can already feel its impact on my health and energy. I encourage you all to incorporate healthy habits into your lifestyle too, and stay tuned with the progress of the field!

ALESSANDRA ZONARI, PhD, is co-founder and Chief Scientific Officer of OneSkin Technologies, a biotechnology company based in San Francisco, CA, focused on developing science-based solutions to maximize our healthspan.
References
  1. Worldometer, Accessed May 18, 2020
  2. Williamsom, E et al. OpenSAFELY: factors associated with COVID-19- related hospital death in the linked electronic health records of 17 million adult NHS patients.MedRvix. May 07, 2020
  3. Franceschi,C and Campisi, J. Chronic Inflammation (Inflammaging) and Its Potential Contribution to Age-Associated Diseases. The Journals of Gerontology: Series A, Volume 69, Issue Suppl_1, 1 June 2014, Pages S4–S9
  4. Sungnak, W et al. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nature Medicine volume 26, pages 681–687(2020)
  5. Hazeldine, J et al. The impact of ageing on natural killer cell function and potential
  6. Moskalev, A et al. Geroprotectors: A Unified Concept and Screening Approaches. Aging Dis. 2017 May; 8(3): 354–363.
  7. Campbell, JM et al. Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: A systematic review and meta-analysis.Ageing Res Rev. 2017 Nov;40:31-44.
  8. Figueiredo RA, Weiderpass E, Tajara EH, et al. Diabetes mellitus, metformin and head and neck cancer. Oral Oncol. 2016;61:47-54
  9. 9mTORC1 inhibitor protects elderly asthmatics from viral respiratory tract infections
  10. Duggal, NA et al. Can physical activity ameliorate immunosenescence and thereby reduce age-related multi-morbidity? Nat Rev Immunol. 2019 Sep;19(9):563-572
  11. Duggal, NA et al. Major features of immunesenescence, including reduced thymic output, are ameliorated by high levels of physical activity in adulthood. Aging Cell. 2018 Apr; 17(2): e12750.
  12. Bartlett, BD et al. Habitual physical activity is associated with the maintenance of neutrophil migratory dynamics in healthy older adults. Brain Behav Immun. 2016 Aug; 56: 12–20.