Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Jan:83:101805.
doi: 10.1016/j.arr.2022.101805. Epub 2022 Nov 21.

Major depression and the biological hallmarks of aging

Erica C Lorenzo  1 , George A Kuchel  1 , Chia-Ling Kuo  2 , Terrie E Moffitt  3 , Breno S Diniz  4
Affiliations
Review

Major depression and the biological hallmarks of aging

Erica C Lorenzo et al. Ageing Res Rev. 2023 Jan.

Abstract

Major depressive disorder (MDD) is characterized by psychological and physiological manifestations contributing to the disease severity and outcome. In recent years, several lines of evidence have suggested that individuals with MDD have an elevated risk of age-related adverse outcomes across the lifespan. This review provided evidence of a significant overlap between the biological abnormalities in MDD and biological changes commonly observed during the aging process (i.e., hallmarks of biological aging). Based on such evidence, we formulate a mechanistic model showing how abnormalities in the hallmarks of biological aging can be a common denominator and mediate the elevated risk of age-related health outcomes commonly observed in MDD. Finally, we proposed a roadmap for novel studies to investigate the intersection between the biology of aging and MDD, including the use of geroscience-guided interventions, such as senolytics, to delay or improve major depression by targeting biological aging.

Keywords: Biology of aging; Cellular; Geroscience; Late-life depression; Major depression; Senescence.

PubMed Disclaimer

Conflict of interest statement

Conflicts of interest All authors have no conflict of interest to report.

Figures

Figure 1:
Figure 1:
Hallmarks of biological aging in MDD. Major depressive disorder can show changes in many different hallmarks of biological aging.
Figure 2:
Figure 2:
Mechanistic model linking the hallmarks of biological aging with adverse health outcomes in MDD. Major depressive disorder (MDD) triggers abnormalities in many hallmarks of biological aging which can be independent of the primary etiological mechanisms of the MDD. It is not clear how MDD triggers the dysregulation of different hallmarks of biological or what is the cascade or hierarchy of changes. However, once these biological processes are activated, they may work in concert and interact among themselves leading to a self-perpetuating deleterious cycle of damage accumulation and diminished resilience to endogenous and exogenous insults (i.e., homeoestenosis). If this deleterious cycle remains unchecked, it can manifest clinically as different adverse health outcomes commonly observed among individuals with MDD.
See this image and copyright information in PMC

References

    1. Abe N, Uchida S, Otsuki K, Hobara T, Yamagata H, Higuchi F, Shibata T, Watanabe Y, 2011. Altered sirtuin deacetylase gene expression in patients with a mood disorder. J Psychiatr Res 45, 1106–1112. - PubMed
    1. Aberg KA, Dean B, Shabalin AA, Chan RF, Han LKM, Zhao M, van Grootheest G, Xie LY, Milaneschi Y, Clark SL, Turecki G, Penninx B, van den Oord E, 2020. Methylome-wide association findings for major depressive disorder overlap in blood and brain and replicate in independent brain samples. Mol Psychiatry 25, 1344–1354. - PMC - PubMed
    1. Ahmadian AJ, Lin JE, Neylan TC, Woolley JD, O’Donovan A, Cohen BE, 2020. Social integration and inflammation in individuals with and without posttraumatic stress disorder. Brain Behav Immun 89, 168–174. - PMC - PubMed
    1. Aizenstein HJ, Baskys A, Boldrini M, Butters MA, Diniz BS, Jaiswal MK, Jellinger KA, Kruglov LS, Meshandin IA, Mijajlovic MD, Niklewski G, Pospos S, Raju K, Richter K, Steffens DC, Taylor WD, Tene O, 2016. Vascular depression consensus report - a critical update. BMC Med 14, 161. - PMC - PubMed
    1. Ampo E, Mendes-Silva AP, Goncalves V, Bartley JM, Kuchel GA, Diniz BS, 2022. Increased Levels of Circulating Cell-Free mtDNA in the Plasma of Subjects With Late-Life Depression and Frailty: A Preliminary Study. Am J Geriatr Psychiatry 30, 332–337. - PMC - PubMed

Publication types