Major depression, physical health, and abnormalities in molecular markers of senescence Summary Previous studies suggested the role of cellular senescence in late-life depression (LLD). However, it is unclear how this finding relates to common features of LLD, such as medical and cognitive problems. We applied factor analyzes to an extensive battery of clinical variables in 426 people with LLD. Here we test the relationship between these factors, age and sex, with an index of cellular senescence based on 22 phenotypic secretory proteins associated with senescence. We found four factors : ’severity of depression and anxiety’, ’cognitive functioning’, ’cardiovascular and cardiometabolic health’ and ’blood pressure’ . A higher senescence-associated secretory phenotype index was associated with worse “ cognitive functioning” and “cardiovascular and cardiometabolic health ,” but not with “severity of depression and anxiety . ” These findings highlight the role of cellular senescence in poorer physical and cognitive health in LLD. They are consistent with the view that concurrent medical burdens and their associated disabilities are part of an accelerated aging phenotype in late-life depression (LLD). |
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“These patients show evidence of accelerated biological aging and poor physical and brain health,” which are the main drivers of this association, says Breno Diniz, a geriatric psychiatrist at UConn School of Medicine and author of the study, which appears in Nature Mental . Health .
Diniz and his colleagues at several other institutions looked at 426 people with late-life depression. They measured the levels of proteins associated with aging in each person’s blood. When a cell ages, it begins to function differently, less efficiently than a "young" cell. It often produces proteins that promote inflammation or other unhealthy conditions, and those proteins can be measured in the blood. Diniz and the other researchers compared the levels of these proteins with measures of the participants’ physical health, medical problems, brain function and severity of depression.
To their surprise, the severity of a person’s depression seemed unrelated to their level of accelerated aging. However, they found that accelerated aging was associated with poorer overall cardiovascular health . People with higher levels of proteins associated with aging were more likely to have high blood pressure, high cholesterol, and multiple medical problems. Accelerated aging was also associated with worse performance on tests of brain health, such as working memory and other cognitive skills.
“Those two findings open opportunities for preventive strategies to reduce the disability associated with major depression in older adults and to prevent the acceleration of biological aging,” says Diniz.
Researchers are now looking at whether therapies to reduce the number of aging "senescent" cells in a person’s body can improve depression in later life. They are also looking for specific sources and patterns of proteins associated with aging, to see if this could lead to personalized treatments in the future.
Previous work suggested a critical role of cellular senescence and an increased SASP index in LLD compared to non-depressed older adults. The present study extended these findings by examining variables related to the SASP index in individuals with LLD. Our results highlighted an association between a high SASP index and poor physical health. Furthermore, the SASP index was associated with age and sex, and cognitive functioning in females. In contrast, the SASP index was not associated with the severity of depression or anxiety (figure).
Final message The present study aimed to understand variables associated with biological senescence status and an increased senescence-associated secretory phenotype (SASP) index in late-life depression (LLD). Physical health demonstrated the strongest association with the senescence-associated secretory phenotype (SASP) index. Additionally, age, sex, and cognitive functioning were associated with the SASP index. The severity of depression and anxiety was not related to the SASP index. Therefore, our findings highlight the importance of physical health for senescence and cellular aging in late-life depression (LLD). Longitudinal studies are needed to examine the complex relationship between LLD, physical health, and aging. |
