Association of Molecular Senescence Markers in Late-Life Depression With Clinical Characteristics and Treatment Outcome

Diniz, Breno S.; Mulsant, Benoit H.; Reynolds, Charles F.; Blumberger, Daniel M.; Karp, Jordan F.; Butters, Meryl A.; Mendes‐Silva, Ana Paula; Vieira, Érica Leandro Marciano; Tseng, George C.; Lenze, Eric J.

doi:10.1001/jamanetworkopen.2022.19678

Cited by 13 publications

(12 citation statements)

References 77 publications

(154 reference statements)

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“…https://doi.org/10.1038/s44220-023-00033-z Finally, in a longitudinal study of a subsample of the participants included in the present analysis, we have shown that a higher SASP index at baseline independently predicted a lower remission rate to venlafaxine treatment 29 .…”

Section: Articlesupporting

confidence: 48%

“…On the basis of these SASP markers 27 , our group developed a peripheral SASP index comprising 22 proteins. We validated the SASP index in several studies 28,29 and consistently found a higher SASP index in individuals with LLD compared with healthy individuals 28,30,31 , suggesting that the SASP index might be a marker for accelerated ageing in LLD.…”

Section: Resultsmentioning

confidence: 65%

“…In this study, we used the SASP index as a systemic measure of biological cellular senescence status. We have used the SASP index in several previous depression studies involving over 1,000 individuals and a longitudinal follow-up [28][29][30][31]67 . In addition, several other groups have used a subset of the SASP proteins and reported a relationship between these proteins and frailty, negative post-surgery outcomes or concussions 68,69 .…”

Section: Articlementioning

confidence: 99%

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Major depression, physical health and molecular senescence markers abnormalities

et al. 2023

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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 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’. These findings highlight the role of cellular senescence in poorer physical and cognitive health in LLD. They are consonant with the viewpoint that co-occurring medical burdens and their associated disabilities are part of a phenotype of accelerated ageing in LLD.

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Section: Articlesupporting

confidence: 48%

Section: Resultsmentioning

confidence: 65%

Section: Articlementioning

confidence: 99%

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Major depression, physical health and molecular senescence markers abnormalities

et al. 2023

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“…Our previous studies have shown key inflammatory factors part of the SASP are strongly correlated with MDD, medical comorbidities, and severity of cognitive impairment (Diniz et al, 2019;Seitz-Holland et al, 2023). Our previous studies also suggest that higher SASP index scores are correlated with higher rates of non-remission of MDD following treatment (Diniz et al, 2022). MDD has also been associated with telomere attrition and DNA damage (Diniz et al, 2018;Gonçalves et al, 2021;Mendes-Silva et al, 2021;Vieira et al, 2021).…”

Section: Introductionmentioning

confidence: 75%

Unraveling the association between major depressive disorder and senescent biomarkers in immune cells of older adults: a single-cell phenotypic analysis

Lorenzo,

Figueroa,

Demirci

et al. 2024

Front. Aging

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Background: Little is known about the prevalence of cellular senescence among immune cells (i.e., immune cells expressing senescence markers, iSCs) nor is there a gold-standard to efficiently measure iSCs. Major depressive disorder (MDD) in older adults has been associated with many hallmarks of senescence in whole blood, leukocytes, and plasma, supporting a strong connection between iSCs and MDD. Here, we investigated the prevalence and phenotype of iSCs in older adults with MDD. Using a single-cell phenotypic approach, circulating immune cells were examined for iSC biomarkers and their relationship to depression and inflammation.Results: PBMCs from older adults with MDD (aged 69.75 ± 5.23 years) and healthy controls (aged 71.25 ± 8.8 years) were examined for immune subset distribution and senescence biomarkers (i.e., lack of proliferation, senescence-associated heterochromatin foci (SAHF), and DNA damage). Dual-expression of SAHF and DNA damage was categorized by low, intermediate, and high expression. A significant increase in the number of high expressing total PBMCs (p = 0.01), monocytes (p = 0.008), a trending increase in the number of high expressing CD4 T cells (p = 0.06) was observed overall in those with MDD. There was also a significantly lower proportion of intermediate expressing cells in monocytes and CD4 T cells in MDD (p = 0.01 and p = 0.05, respectively). Correlation analysis revealed associations between iSCs and mRNA expression of factors related to SASP and immune cell function.Conclusion: MDD is associated with increased senescent cell biomarkers in immune cell populations delineated by distinct levels of SAHF and DNA damage. Inflammatory markers might serve as potent indicators of iSC burden in MDD.

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“…An accelerated aging hypothesis of LLD implies a bidirectional process [ 206 ]. Depressed older adults exhibit an advanced biological age on a multibiomarker index of metabolic and inflammatory measures [ 207 , 208 ] and on structural MRI, where they appear approximately 4 years older than nondepressed individuals [ 198 ]. This accelerated brain aging is further associated with disability and cognitive performance [ 198 ], with depression severity moderating the relationship between brain age and some cognitive measures.…”

Section: Depression and Accelerated Agingmentioning

confidence: 99%

Biological factors influencing depression in later life: role of aging processes and treatment implications

Szymkowicz,

Gerlach,

Homiack

et al. 2023

Transl Psychiatry

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Late-life depression occurring in older adults is common, recurrent, and malignant. It is characterized by affective symptoms, but also cognitive decline, medical comorbidity, and physical disability. This behavioral and cognitive presentation results from altered function of discrete functional brain networks and circuits. A wide range of factors across the lifespan contributes to fragility and vulnerability of those networks to dysfunction. In many cases, these factors occur earlier in life and contribute to adolescent or earlier adulthood depressive episodes, where the onset was related to adverse childhood events, maladaptive personality traits, reproductive events, or other factors. Other individuals exhibit a later-life onset characterized by medical comorbidity, pro-inflammatory processes, cerebrovascular disease, or developing neurodegenerative processes. These later-life processes may not only lead to vulnerability to the affective symptoms, but also contribute to the comorbid cognitive and physical symptoms. Importantly, repeated depressive episodes themselves may accelerate the aging process by shifting allostatic processes to dysfunctional states and increasing allostatic load through the hypothalamic–pituitary–adrenal axis and inflammatory processes. Over time, this may accelerate the path of biological aging, leading to greater brain atrophy, cognitive decline, and the development of physical decline and frailty. It is unclear whether successful treatment of depression and avoidance of recurrent episodes would shift biological aging processes back towards a more normative trajectory. However, current antidepressant treatments exhibit good efficacy for older adults, including pharmacotherapy, neuromodulation, and psychotherapy, with recent work in these areas providing new guidance on optimal treatment approaches. Moreover, there is a host of nonpharmacological treatment approaches being examined that take advantage of resiliency factors and decrease vulnerability to depression. Thus, while late-life depression is a recurrent yet highly heterogeneous disorder, better phenotypic characterization provides opportunities to better utilize a range of nonspecific and targeted interventions that can promote recovery, resilience, and maintenance of remission.

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Association of Molecular Senescence Markers in Late-Life Depression With Clinical Characteristics and Treatment Outcome

Cited by 13 publications

References 77 publications

Major depression, physical health and molecular senescence markers abnormalities

Major depression, physical health and molecular senescence markers abnormalities

Unraveling the association between major depressive disorder and senescent biomarkers in immune cells of older adults: a single-cell phenotypic analysis

Biological factors influencing depression in later life: role of aging processes and treatment implications

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