Fight Aging!

Inflammatory signaling may be influential in major depressive disorder. For any condition in which inflammation is important, attention should be given to the possible role of cellular senescence, given the advent of senolytic therapies to clear these cells. Senescent cells grow in number throughout the body with age, and while never a large fraction of all cells, they energetically generate pro-inflammatory signals. Here, researchers discuss the sometimes there, sometimes not correlation between burden of senescent cells and incidence of major depressive disorder in later life.

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 analyses to an extensive battery of clinical variables in 426 individuals with LLD. Here we tested the relationship between these factors, age and sex, with an index of cellular senescence based on 22 senescence-associated secretory phenotype (SASP) proteins.

We found four factors: 'depression and anxiety severity', 'cognitive functioning', 'cardiovascular and cardiometabolic health' and 'blood pressure'. A higher senescence-associated secretory phenotype index was associated with poorer 'cognitive functioning' and 'cardiovascular and cardiometabolic health' but not with 'depression and anxiety severity'.

When interpreting this finding, it is critical to note that it does not contradict our previous studies that have consistently demonstrated an increased SASP index in individuals with a major depressive disorder compared with non-depressed older adults. However, it suggests that the SASP index is more closely associated with physical health and cognitive functioning than with the severity of depression and anxiety symptoms within individuals with LLD. The question of how depressive symptoms interact with the pathophysiology of major depression is fiercely discussed.

Our findings highlight the interactive effect between LLD and physical burden. Previous research has demonstrated that depression frequently occurs in individuals with chronic illness and amplifies the disability and disablement associated with co-occurring physical illness and cognitive impairment. In addition, depression undermines adherence to co-prescribed pharmacotherapy for medical diseases and reduces healthy lifestyle choices. Therefore, evidence-based treatment of depression may also reduce mortality risk secondary to physical illness, such as cancer. On the other hand, co-occurring physical burden moderates the long-term response to antidepressant treatment and renders the individual's response more brittle.

Link: https://doi.org/10.1038/s44220-023-00033-z