Late life depression: Bridging the gap with new perspectives on aging

In a recent study published in Frontiers in Medicine, researchers explore the interplay between late life depression (LLD) and aging.

Study: Late life depression and concepts of aging: an emerging paradigm. Iamge Credit: Ground Picture /

Characterizing LLD

The growing incidence of LLD in individuals over 65 of age is a global concern. The World Health Organization (WHO) emphasizes the management of mental health issues, especially depression, for sustainable healthy aging.

The three main categories of biological aging include cerebrovascular aging, inflammation with dopamine depletion, and oxidative stress linked to energy imbalances. These correspond to three LLD phenotypic subtypes including depressed with executive dysfunction, inflamed-slowed, and frail-fatigued.

Coexisting neurodegenerative processes enhance these phenotypes and are marked by cognitive issues, decreased processing speed, impaired speech, abnormal gait, and signs of dwindling cognitive reserves.

Neural networks in aging and LLD

Progress in mapping neural networks has improved the understanding of depression and related changes within and between these networks. Using tools like functional magnetic resonance imaging (MRI) and neuroimaging, recent studies have linked aging brain alterations to structural and functional shifts.

More specifically, LLD is associated with abnormalities in the ventral limbic affective system leading to dysphoria, the frontal striatal reward network resulting in anhedonia, disrupted default mode network connectivity causing depressive rumination, and the dorsal cognitive control network which produces cognitive deficits and reduced control over negative thoughts and emotions.

The concept of aging concept represents the combined effects of deteriorating systems within the broader aging biology of humans. Previous research has associated both physical frailty and LLD with widespread impairments in biological networks.

The importance of resilience

In psychosocial studies, resilience refers to one's ability to sustain or regain well-being amidst adversity. Physical resilience, though lacking a unanimous definition, often denotes resistance or recovery from functional decline after health challenges. Incorporated into models of successful aging, resilient individuals persevere through hardships, in addition to retaining functional stability and a sense of well-being.

Efforts to define resilience, especially regarding LLD, have identified distinct psychosocial and biological factors. Positive attributes like temperament, attachment levels, personality, beliefs, coping mechanisms, and socio-lifestyle factors have been linked to avoiding depression in older age.

Intrinsic capacity, a concept introduced by the WHO and distinct from resilience, plays a pivotal role in successful aging, as it mediates the interaction between individuals and their environment.

The WHO Function, Disability, and Health (ICF) framework

The concept of intrinsic capacity can be better understood within the framework of the WHO ICF. As compared to the former linear disease-focused model, the ICF perceives a person’s functionality as a result of interactions among health conditions, body functions, participation, environment, and personal factors.

Aging experts argue that intrinsic capacity aligns with "Body Functions" in the ICF. The definition of intrinsic capacity often encompasses cognition, locomotion, sensory integrity, vitality, and psychological capacity. Extensive research on depression demonstrates the strong link between LLD, aspects of the ICF model, and intrinsic capacity measurements.


The widespread prevalence of ageism impacts elderly individuals, thereby leading to perceptions of negativity, increased social isolation, and diminished roles in society. This phenomenon is strongly associated with LLD and can be influenced by factors like loss of social identity, diminished employment roles, isolation, and reduced community resources.

Risk factors include loneliness, caregiver stress, sleep disturbances, and addiction. Conversely, faith, hope, and a sense of purpose contribute to depression-free aging. Overall, psychobiological aspects of resilience play a crucial role in shielding individuals from LLD.

Treatment approaches for LLD

Emerging insights into the biology of LLD highlight potential research focuses including controlling neurovascular risks, minimizing oxidative stress, and slowing brain aging. Advanced clinical diagnostics that can characterize LLD phenotypic subtypes could facilitate personalized pharmacological treatments, behavioral strategies, psychotherapy, loneliness interventions, and cognitive exercises.

Exploring new drugs, based on the distinct biochemical and neurotransmitter shifts, may improve the currently modest response rate to LLD antidepressants, especially among the very elderly.

Furthermore, a holistic understanding of LLD biology suggests improved diagnostics and personalized treatments based on specific subtypes. However, treatments exclusively focusing on pharmacological solutions may not consider the broader perspective of successful aging. Society's understanding of depression should transition away from the conventional medical paradigm and instead re-evaluate aging and the role of the elderly within the modern society.

Addressing age-related challenges including social frailty is imperative. Health planners and stakeholders are currently addressing issues like elder isolation and age-related poverty by emphasizing interdisciplinary solutions to promote seniors' active societal participation.

Beyond medication, it is crucial to nurture psychological resilience and emphasize the importance of positive psychology, health, and aging.


While acknowledging the importance of understanding the biology of depression, the authors advocate for an inclusive approach for addressing LLD by emphasizing concepts like resilience, intrinsic capacity, and re-evaluating the societal role of older individuals.

Journal reference:
  • Jacobs, J. M., Baider, L., Goldzweig, G., et al. (2023) Late life depression and concepts of aging: an emerging paradigm. Frontiers in Medicine. doi:10.3389/fmed.2023.1218562
Vijay Kumar Malesu

Written by

Vijay Kumar Malesu

Vijay holds a Ph.D. in Biotechnology and possesses a deep passion for microbiology. His academic journey has allowed him to delve deeper into understanding the intricate world of microorganisms. Through his research and studies, he has gained expertise in various aspects of microbiology, which includes microbial genetics, microbial physiology, and microbial ecology. Vijay has six years of scientific research experience at renowned research institutes such as the Indian Council for Agricultural Research and KIIT University. He has worked on diverse projects in microbiology, biopolymers, and drug delivery. His contributions to these areas have provided him with a comprehensive understanding of the subject matter and the ability to tackle complex research challenges.    


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