The new coronavirus, scientific name Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), inherited the mantle of its brother SARS virus and spread the scope to the whole world.
Now that it is the third year of the outbreak, we are becoming more and more familiar with the new crown, and with the popularization of vaccines and the change of strains, the fatality rate of the new crown is declining. But it is still difficult for us to coexist with the new crown, which is inseparable from the "sequelae" of the new crown, chest pain and palpitations, muscle atrophy, easy exhaustion [1]... One BBC journalist even described herself as 44 years old and "like an 80-something old" 16 months after contracting COVID-19.
So does covid-19 really make people older? A study by mainland scientists published on April 19 in Nature Communication, a sub-issue of the top journal Nature, gave the affirmative answer, that covid-19 infection will accelerate patient aging [3]!
COVID-19 infection accelerates epigenetic aging
The study took blood samples from subjects, including 232 healthy individuals, 194 non-severe COVID-19 patients, and 213 severely ill patients, and used five epigenetic clocks to measure epigenetic age (physiological age) and calculate telomere lengths that also reflect aging. This is because both respond to cellular senescence at different levels, and the results estimated by epigenetic age are more appropriate for showing aging-related changes than the average telomere length [4].
The final results are basically the same: compared with healthy individuals, the epigenetic age growth rate and telomere loss rate of COVID-19 patients are significantly accelerated, and this accelerated aging phenomenon exists in both young and old people [3].
Note: Five epigenetic clocks show an acceleration in physiological age and an acceleration in telomere loss
The researchers then continued to compare healthy, non-severe, and severe conditions, and found that the severity of THE new crown was related to the degree of acceleration of aging: as the severity of the disease increased, epigenetic aging became faster and faster [3]!
Behind the acceleration of aging
So why does COVID-19 infection accelerate aging?
First of all, because the new crown virus can bind to the cell surface angiotensin-converting enzyme 2 (ACE2) receptor through its surface-distributed spike protein "tentacles" and enter the host cell, and the ACE2 receptor is widely distributed, and there are also such receptors on the surface of immune cells, the new crown virus may be able to directly damage immune cells and promote immune aging [5].
Caption: Coronavirus SARS-CoV-2
The second is the inflammatory response, one of the important markers of aging.
On the one hand, because ACE2 has an anti-inflammatory effect, receptors that damage it cause the body's anti-inflammatory ability to decrease, increasing the body's inflammatory response [5].
On the other hand, the body's resistance to the new crown virus can also aggravate the inflammatory response. Retinoic acid-inducing gene-like receptors located on the mitochondria can detect the new coronavirus, signaling an increase in pro-inflammatory factors. T cells, the main force in the fight against viral infections, also promote CD4+ effector cells to release cytokines to induce a stronger inflammatory response when cytotoxic CD8+ cells that degrade infected cells and the viral genome cannot eliminate the virus[5].
In addition, in response to viral infection, the body raises the level of plasminogen activator 1 to neutralize the transmembrane serine protease 2 (TMPRSS2) on host cells that is countered by spike proteins and allows the virus to enter the cell, thereby reducing the infectivity of the new coronavirus. However, plasminogen activator inhibitor 1 is a marker of aging that increases the risk of thromboembolism and coagulation disorders, and also forms a cycle with another aging marker, TGF-β: TGF-β increases in response to the inflammatory response, improves the expression of plasminogen activator inhibitor 1, and then further increases the level of TGF-β, continuously promoting the body's aging [5].
Note: The process by which the new coronavirus enters the host cell, from the Nature Portfolio
Is the impact of COVID-19 infection on life expectancy serious?
But is the impact of COVID-19 on lifespan really serious? not necessarily.
The study by mainland scientists did not specify how much faster COVID-19 infection would cause patients to age, and the blood samples selected by the researchers were basically from patients in the Spanish region from March to September 2020, and the virus strain was not the currently circulating Omikeron [3]. On March 16, the sub-issue of the top journal The Lancet reported that the risk of severe illness in Ami kerong infection was lower. This may mean that the effect on the rate of aging is also smaller [6].
Photo note: "The Lancet" reported on March 16[5]
It is worth noting that the mainland scientists further compared 6 uninfected patients with 6 patients, and distinguished the aggravation and recovery stages of the new crown infection according to the inflammatory markers and the need for respiratory ventilation, and found that the aging rate was different at different stages [3].
Through the Horvath clock invented by the father of epigenetic clocks, they measured that physiological age growth continued to accelerate during the incremental-severe and complex phases of the disease, while slowing down during the recovery period (Figure A), although aging was still faster than in the uninfected period. Similar results were obtained in Hannum and PhenoAge clocks, which showed an acceleration of aging in the incremental-severe phase, while an accelerated slowdown in the complex and convalescent phases [3].
Note: The abscissa coordinates from left to right are uninfected, incremental-severe, complex and convalescent, and it can be seen that the epigenetic clocks of Horvat, Hannum and PheoAge all show accelerated aging in the initial stage of infection and accelerated slowdown in the later stages of disease
Studies of the association between the stage of disease development and the aging state of a single individual also confirm this point: the initial stage of the disease shows accelerated aging, and in the later stages, there is a partial reversal. There are indications that the impact of COVID-19 on life expectancy may be restored! This allows us to be more optimistic.
Note: Changes in epigenetic age and telomere length at different stages of the disease in 6 patients compared with 6 uninfected patients
What is the fight against aging and fighting the epidemic?
The two-way relationship between aging and the new crown, that is, aging will increase the infection rate and severity of the new crown, and the new crown will also accelerate the aging, so that anti-aging and anti-epidemic have become the same thing to a certain extent.
Scientists have found that many anti-aging drugs can play a role in fighting viral infections. Rapamycin, for example, has been found to enhance the response of older adults to influenza vaccines, making vaccines more effective and improving their antiviral immunity, and it acts as an inhibitor of protein synthesis, which has been shown to inhibit replication of the most widely spread HIV subtype of HIV-1 [7-8];
For example, metformin, which is also a first-line drug for diabetes and an anti-aging drug, relies on the synthesis of fatty acids for replication of many viruses, so metformin can interfere with viral replication and host-virus interaction by inhibiting fatty acid synthesis[9];
There are also chloroquine-related compounds that inhibit the aging marker β-galactosidase and are candidates for the prevention and treatment of COVID-19, although efficacy and safety in older adults require more data [10].
These anti-aging drugs and antivirals with potential anti-aging effects have the potential to fight COVID-19, and some studies suggest that they may be able to prevent the acceleration of aging and the accumulation of disease after COVID-19 [5]. This reaffirms once again that aging is the biggest risk factor for all age-related diseases.
The fight against aging continues, and the fight against the epidemic continues, and in contrast, the latter is more likely to achieve complete victory. Since with the efforts of scientists, we can find many anti-aging intervention methods and fight death through scientific methods, what reason is there not to win the battle against the epidemic?
Live trailer
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—— TIMEPIE ——
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[2] BBC News Chinese. (2021, July 24). The long-term "aftermath" of COVID-19: BBC journalists' personal experiences about how to cope. https://www.bbc.com/zhongwen/simp/science-57914413
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