Why Is Age a Factor in COVID-19?

Why Is Age a Factor in COVID-19?

For centuries, people have been searching for the Fountain of Youth. Many thought it was a real fountain where a person could bathe or drink to slow the aging process. While that fountain doesn’t exist, there are several strategies you may use to affect a change internally with external results.

Several factors affect aging, including chronic inflammation that leads to chronic disease. Although inflammation plays an essential role in repairing injury, chronic inflammation may result in health conditions like bowel diseases, arthritis, diabetes and heart disease.1

Although many times you won’t notice early visible signs of chronic inflammation, there is mounting evidence that it is an underlying factor in chronic disease.2 There is also evidence that natural remedies are effective in reducing inflammation and thus reducing the potential for chronic disease.3

Underlying or baseline inflammation can exacerbate the aging process and raise the risk of severe infectious disease, as has been demonstrated by the numbers of people 65 and older who have died from COVID-19. The Centers for Disease Control and Prevention reports that 8 of every 10 deaths from COVID-19 are people age 65 and older.4

Inflammaging Associated With Frailty and Increased Death

Inflammaging is the “chronic low-grade inflammation occurring in the absence of overt infection.”5 This type of damaging inflammation negatively impacts immunity. Researchers hope that by preventing baseline inflammation, they can improve the immune response.

This is a significant pathway to help reduce the severity of disease in older individuals infected with SARS-CoV-2.6 This novel coronavirus brings about a serious condition in the elderly, increasing morbidity and mortality.

Severe disease often presents with excessive inflammation in the pulmonary system, especially in older individuals with high baseline C-reactive protein, indicating a heightened inflammatory response. Data show that inflammation biomarkers like this are relatively accurate predictors of mortality in the elderly, increasing their susceptibility to all sorts of maladies.7

In a paper published in Science Mag, the authors discuss some of the cellular and systemic challenges faced by older adults in their fight against infectious diseases, including COVID-19.8

They hypothesize that a low-grade inflammatory response may be the result of several mechanisms, including a compromised gut microbiome and obesity. As the body ages, it also slowly loses the ability to clear dead and dying cells, which subsequently increases inflammatory activity.

These senescent cells are no longer able to divide, and they accumulate throughout the body. However, they are not “silent” but rather can secrete inflammatory cytokines and other inflammatory molecules that can trigger inflammation and dysfunction.

Reducing Baseline Inflammation May Lower Disease Severity

If you have a baseline inflammatory response, the flu vaccine may not be as effective for you as expected.9 Researchers have improved the body’s response to an antigen by administering an inhibitor,10 which suggests that baseline inflammation has a significant effect on the immune system.

The authors also theorize this may be relevant to older individuals with severe respiratory tract disease. As we age, the number of senescent cells and the level of baseline inflammation rises. Another way to improve immunity and reduce inflammation, then, may be to eliminate them.

This has prompted the development of senolytic therapies to do just that. The relationship between baseline inflammation and severe disease in older individuals with COVID-19 has not yet been defined, but one hypothesis is that the senescent cells and pre-existing inflammatory cells amplify the effects of COVID-19 in the respiratory tract.

Another theory is that the baseline inflammation in the body is not damaging on its own, but it may start a cellular cascade, which heightens inflammation with an infection. In addition to this, senescent cells can bring about more inflammation. Their buildup in the pulmonary tract may contribute to an increase in severe disease.

While the authors of the perspective published in Science Mag promote vaccination against SARS-CoV-2, they also point out that any effective treatment for the elderly may require a combination of antiviral and anti-inflammatory treatments.

Clearing Senescent Cells With Senolytics

Senolytic therapies were initially developed with the aim of reducing the severity of disease in the elderly and making an impact on the meteoric rise in chronic diseases, including Type 2 diabetes, heart disease and idiopathic pulmonary fibrosis (IPF).11

However, it’s not a big leap to predict that the beauty industry may use the science to develop a new line of products to slow the aging process. According to Mayo Clinic researchers, preclinical data have demonstrated the potential for drugs to selectively encourage apoptosis in dying cells and have a positive effect on:12

Cardiac dysfunction

Type 2 diabetes

Liver steatosis

Vertebral disk degeneration

Pulmonary fibrosis

Vascular hyporeactivity and calcification


Radiation-induced damage

The possibility of impacting multiple diseases and functional deficits at the same time excites the scientific community because it can move geriatric medicine from largely reacting to disease to preventing it and thus slowing the aging process.

The potential to extend life and reduce disease has prompted some scientists to investigate the use of antibiotics as senolytics, despite the dangerously high level of antibiotic-resistant bacteria.13 In 2018, a team from the University of Salford in the U.K. published a study with “the goal of identifying and repurposing FDA-approved antibiotics, for the targeting of the senescent cell population.”14

The lab-based study involved human fibroblasts, and the team identified Azithromycin and Roxithromycin as drugs that showed senolytic activity. Another drug in the same family, Erythromycin, did not have the same effect.

In an interview with Health Europa, one member of the research team, Michael Lisanti, said he believes the next steps are clinical trials. He acknowledges they haven’t examined the relationship to antimicrobial resistance and that azithromycin is not an ideal antibiotic in this “context.” He went on to say:15

“Potentially in the future, once researchers identify what it is about the azithromycin that is causing the senescent cells to die, they could develop future drugs — azithromycin is a stepping stone in this context …”

You May Have a Senolytic in Your Vitamins — Quercetin

Although not all scientists agree,16 many argue that quercetin demonstrates senolytic properties. Early laboratory trials using human fibroblast cells showed quercetin “influence(s) cellular life span, survival and viability of HFL-1 primary human fibroblasts.”17

Early results from a clinical trial with chemotherapy agent Dasatinib and quercetin showed the combination of the two may lower the number of senescent cells in people with diabetic kidney disease.18

While encouraging, as one writer points out, “synergy with other compounds is a very different story from unilateral effects.”19 Yet, in other studies using only quercetin, its effect on lung fibrosis was found to diminish inflammation in the lab and to reduce pulmonary collagen deposits in an animal model after induced damage.20

The researchers went on to test the singular use of quercetin in an animal model with induced lung fibrosis and found:21

“Quercetin inhibited the progression of lung fibrosis, reduced the expression of senescent cell markers and SASP, and promoted overall health benefit in an experimental fibrosis model in aged mice. Last, we conclude that the data provided in our study are very promising and may add to current therapeutic strategies for IPF and other fibrotic disorders.”

Metabolic Therapies on the Horizon

Metabolic therapies are another strategy that may be used to halt the progression of viral disease. In the new field of immunometabolism research, scientists have discovered that metabolism has an influence on altering viral replication and affecting the body’s response to a pathogen.

One of the strategies showing promise is ketosis. In a paper published in the journal Cell, scientists said they believe the principal ketone body beta-hydroxybutyrate (BHB) is highly effective, and is:22

“… a highly efficient oxidative fuel and signaling metabolite. BHB has been shown to have diverse molecular effects, including metabolic regulation; increased cellular resistance to oxidative stress; inhibition of nuclear factor κB (NF-κB) signaling via HCAR2 receptor binding; decreased activity of components of the innate immune system, such as the nonobese diabetic (NOD)-, leucine-rich repeat (LRR)-, and pyrin domain-containing protein 3 (NLRP3) inflammasome;decreased systemic inflammatory burden; modifying gene expression; and acting as a fuel in the context of energetic stress.”

Clinical trials are currently underway to investigate the use of a ketogenic diet to reduce the signs of aging, prevent heart failure and neurodegeneration and manage diabetes. Researchers hope that using a ketogenic diet on intubated patients who are confirmed positive for COVID-19 may help reverse the progression of the disease.23

The authors of the paper warn it’s important to distinguish between ketoacidosis, which is a metabolic dysfunction leading to uncontrolled ketone accumulation, and adaptive physiological levels of ketosis in response to eating a low carbohydrate diet.

In intubated patients in the ICU, they believe using an exogenous source of ketones rather than inducing ketosis through prolonged fasting will have a greater positive effect.

For those who are not intubated, the authors write of potential immunological advantages when a ketogenic metabolic state is initiated. Researchers have also found medications that mimic caloric restriction, such as metformin, can reduce the inflammatory response because they get rid of senescent cells in much the same way that senolytic agents work.24

Fasting and Cyclical Ketogenic Diet Raise Ketone Levels

In addition to quercetin, you may have a significant impact on your health and immune system by practicing a cyclical ketogenic eating plan. There are several other benefits including losing weight, fighting inflammation, reducing appetite and lowering insulin levels.

As I’ve written in the past, limiting carbs and decreasing your eating window to 6-8 hours may help protect you against influenza. A team from Yale School of Medicine tested a theory in a small animal model study and found “… that the consumption of a low-carbohydrate, high-fat ketogenic diet (KD) protects mice from lethal IAV infection and disease.”25

By integrating a cyclical approach to the ketogenic diet, you can increase the health benefits and have greater flexibility in your meal planning. I describe an approach to this in “Will Eating Keto Help Prevent Flu?” In another article I discussed my KetoFast protocol to help reduce metabolic dysfunction.



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