COVID-19 is an emergent disease of aging.

COVID-19 is an ongoing pandemic caused by the SARS-CoV-2 coronavirus that poses one of the greatest challenges to public health in recent years. SARS-CoV-2 is known to preferentially target older subjects and those with pre-existing conditions, but the reason for this age dependence is unclear. Here, we found that the case fatality rate for COVID-19 grows exponentially with age in all countries tested, with the doubling time approaching that of all-cause human mortality. In addition, men and those with multiple age-related diseases are characterized by increased mortality. Moreover, similar mortality patterns were found for all-cause pneumonia. We further report that the gene expression of ACE2, the SARS-CoV-2 receptor, grows in the lung with age, except for subjects on a ventilator. Together, our findings establish COVID-19 as an emergent disease of aging, and age and age-related diseases as its major risk factors. In turn, this suggests that COVID-19, and deadly respiratory diseases in general, may be targeted, in addition to antiviral approaches, by approaches that target the aging process.

Germline burden of rare damaging variants negatively affects human healthspan and lifespan.

Heritability of human lifespan is 23-33% as evident from twin studies. Genome-wide association studies explored this question by linking particular alleles to lifespan traits. However, genetic variants identified so far can explain only a small fraction of lifespan heritability in humans. Here, we report that the burden of rarest protein-truncating variants (PTVs) in two large cohorts is negatively associated with human healthspan and lifespan, accounting for 0.4 and 1.3 years of their variability, respectively. In addition, longer-living individuals possess both fewer rarest PTVs and less damaging PTVs. We further estimated that somatic accumulation of PTVs accounts for only a small fraction of mortality and morbidity acceleration and hence is unlikely to be causal in aging. We conclude that rare damaging mutations, both inherited and accumulated throughout life, contribute to the aging process, and that burden of ultra-rare variants in combination with common alleles better explain apparent heritability of human lifespan.

Most living things undergo biological changes as they get older, a process that we generally refer to as aging. Despite being a widespread phenomenon, scientists do not fully understand why we age, though it appears that a combination of genetics and lifestyle factors, such as diet, play a role in influencing lifespan. Aging increases the risk of developing a wide range of diseases, including cancer, Alzheimer's disease and diabetes. As such, finding ways to slow the aging process would help to postpone the onset of illness and potentially improve health in old age. Genes are thought to be responsible for between one quarter and one third of the variation in human lifespans. The relationship between genes, aging and lifespan is complex and not well understood. One set of rare genetic changes that have been shown to have significant effects on diseases are called protein truncation variants (PTVs). PTVs cause damage by altering the production of certain proteins. There are many possible PTVs and people can be born with them or they can develop them in some cells later in life. The full influence of PTVs on aging is not known. Shindyapina, Zenin et al. have now studied observational data collected from two groups of over 40,000 people in the UK. Both groups recorded over 1,000 deaths, and the study examined the influence of PTVs on natural lifespan. The results show that each person is born with an average of six PTVs, which can vary in the impact that they have on aging. Having more, or more severe, PTVs could reduce life expectancy on average by 1.3 years. PTVs affect both total lifespan and healthy lifespan, the period of time lived prior to developing the first age-related disease. While PTVs that people are born with have a significant effect on aging, this study also showed that PTVs that are acquired due to spontaneous mutations through a person's life have much less of an impact. This is a key insight into the relationship between genes and aging. These discoveries could help in using genetics to anticipate future health, it also helps to identify some of the biological systems that have a role in aging. This could lead to new ways to delay the aging process and its effects on health.