It is well established that mental health conditions, including substance use disorders, are associated with premature mortality. A meta-analysis 1 has demonstrated that this association holds across a range of diagnoses. Although the effect is stronger for schizophrenia, depression and anxiety contribute to more deaths overall because of their high prevalence rates. Moreover, more than two-thirds of associated deaths were explained by natural causes. 1 The next logical questions, then, are as follows: which mechanisms underlie this association, and can they can be mitigated? In the current issue of JAACAP, Clark et al. 2 aim to tie mental health symptoms and substance use to the acceleration of biological aging.