SENS Research Foundation here explains why COVID-19, like near all infectious disease, is far worse for the old. It isn’t just a matter of the decline of immune function, though that is the bulk of it. Older people have a greater burden of damage and dysfunction that makes them less resilient in many other ways. Rising mortality due to infectious disease with age is the result of both (a) a greater likelihood of severe infection due to immune aging, and (b) that the individual is less likely to survive a severe infection due to general frailty. Tens of thousands die every year in the US from seasonal influenza; that is largely ignored, taken as a fact of life when considered at all. But the research and medical communities are on the verge of being able to reverse the consequences of aging, to develop rejuvenation therapies that will improve immune function and resilience in the old. This work needs greater support than it presently receives if we are to see significant progress over the next decade.

Through all the daily updates on the sick and the dead, on testing and hospital capacity and changing public health guidance, there remains one constant: by far the greatest predictor of death from the COVID-19 pandemic is age. The so-called comorbidities predisposing patients to death from COVID-19 – chronic lung diseases, damaged kidneys and hearts, high blood pressure, diabetes – are themselves aspects of aging, erupting in their distinctive ways in particular tissues. Flattening this “demographic curve” of degenerative aging would reduce COVID-19 to a disease similar in impact to an average recent flu season (and make future flu seasons less deadly), while also putting an end to the staggering toll of age-related death and debility that ticks on in the background even now, day in and day out, pandemic or none.

The most obvious link between aging and COVID-19 is the aging of the immune system, or immunosenescence. Older people mount a much weaker and less complete immune response to both infection and vaccine, even as they suffer increasingly from overactive parts of the immune response, including autoimmunity and chronic inflammation. In today’s pandemic, COVID-19 patients suffer from an exhaustion of natural killer (NK) and CD8+ (“killer”) T-cells. Whereas T-cells and B-cells are specialists, focused on eliminating specifically-identified threats (such as cells infected with specific viruses), NK cells are sentinels patrolling the perimeter of a military camp, on the lookout for anything that looks like it doesn’t belong. Long before the pandemic hit, we knew that NK cells lose much of their effectiveness with age, meaning that aging people already come into the fight against infections like SARS-CoV-2 with these critical early responders weakened.

We’ve known for a while that the age-related loss of lung function is a massive driver of risk of death from pneumonia. Aging people not only have fewer functional alveoli available, but progressively lose the ability to inhale and exhale deeply to compensate for alveoli taken offline by the infection. Continuing research suggests that eliminating senescent cells in the lung may preserve and restore youthful lung function, leaving the lungs better prepared to endure the attack of the SARS-CoV-2 virus and other causes of pneumonia. Senolytic drugs, which selectively kill senescent cells, have been shown to reverse lung fibrosis and other tissue fibrosis in aging mice. Studies in aging mice demonstrate that ablating senescent cells restores youthful lung compliance, suggesting an opportunity to do the same with other senescent-cell elimination strategies, such as restoring the ability of NK cells to eliminate them from tissues.

Like the pandemic, aging touches all of us. It creeps silently through our tissues, progressively crippling our minds and bodies, and eventually killing us if we don’t die first of accident, violence, or other abrupt age-independent causes. In COVID-19, the damage caused by aging is the largest factor in determining who lives and who dies, even if the trigger was pulled by a virus spread by globalization. The need for rejuvenation biotechnologies as part of medicine has never been clearer, and so we strengthen our resolve. Restoring our cells and tissues to youthful vigor will allow us to step out of our ancient lockdown and into a bright future.