Stress response biomarkers of resilience
Stress response biomarkers include endocrine, immune, and inflammatory indices. Stress has been identified as a factor in inflammatory responses. Stress-related overstimulation of the HPA axis may increase the risk of LLD.22 Numerous studies have demonstrated an association between increased levels of peripheral proinflammatory cytokines and depressive symptoms in older adults.23 Interleukin-6 (IL-6) has been increasingly linked with depressive symptoms and poor memory performance in older adults.9 There also appears to be an interaction of inflammatory and vascular processes predisposing to LLD, as increased levels of IL-6 and C-reactive protein have been associated with higher white matter pathology.9 Additionally, proinflammatory cytokines impact monoamine neurotransmitter pathways, leading to a reduction in tryptophan and serotonin synthesis, disruption of glucocorticoid receptors, and a decrease in hippocampal neurotrophic support.9 Alexopoulos et al24 further explain that a prolonged CNS immune response can affect emotional and cognitive network functions related to LLD and has a role in the etiology of depressive symptoms in older adults.
Cardiovascular comorbidity and autonomic nervous system dysfunction
Many studies have revealed evidence of a bidirectional association between cardiovascular disease and depression.25 Dysregulation of the autonomic nervous system (ANS) is an underlying mechanism that could explain the link between cardiovascular risk and MDD via heart rate variability (HRV), though research examining age-related capacities provide conflicting data.25,26 HRV is a surrogate index of resting cardiac vagal outflow that represents the ability of the ANS to adapt to psychological, social, and physical environmental changes.27 Higher overall HRV is associated with greater self-regulating capacity, including behavioral, cognitive, and emotional control.28 Additionally, higher HRV may serve as a biomarker of resilience to the development of stress-related disorders such as MDD. Recent studies have shown an overall reduction in HRV in older adults with LLD.29 When high- and low-frequency HRV were investigated separately, only low-frequency HRV was significantly reduced in patients with depression.29 One explanation is that older adults with depression have impaired or reduced baroreflex sensitivity and gain, which is often associated with an increased risk of mortality following cardiac events.30 More research is needed to examine the complex processes required to better characterize the correlation between resilience in cardiovascular disease and autonomic dysfunction.
The Box6,31,32 describes the relationship between markers of cellular health and resilience.
Among the biomarkers of resilience, telomere length and telomerase activity serve as biomarkers of biological aging that can differ from the chronological age and mark successful anti-aging, stress-reducing strategies.31 Telomerase, the cellular enzyme that regulates the health of cells when they reproduce (preserving the telomeres, repetitive DNA strands at the ends of chromosomes), is associated with overall cell health and cellular biological age.31 When telomerase is reduced, the telomeres in a cell are clipped, causing the cells to age more rapidly as the telomeres get shorter through the process of cellular reproduction.31 Psychological stress may play a significant role in telomerase production and subsequent telomere length.32 Lavretsky et al32 evaluated the effect of brief daily yogic meditation on depressive symptoms and immune cell telomerase activity in a family of dementia caregivers with mild depressive symptoms. Brief daily meditation practice led to significant lower levels of depressive symptoms that was accompanied by an increase in telomerase activity, suggesting improvement in stress-induced cellular aging.6,32
There is increasing interest in improving older adults’ physical and emotional well-being while promoting resilience through stress-reducing lifestyle interventions such as MBTs.33 Because MBTs are often considered a natural and safer option compared to conventional medicine, these interventions are rapidly gaining popularity in the United States.33,34 According to a 2017 National Health Survey, there were 5% to 10% increases in the use of yoga, meditation, and chiropractic care from 2012 to 2017, with growing evidence supporting MBTs as minimally invasive, cost-effective approaches for managing stress and neurocognitive disorders.35 In contrast to pharmacologic approaches, MBTs can be used to train individuals to self-regulate in the face of adversity and stress, thus increasing their resilience.
MBTs can be divided into mindful movement exercises and meditative practices. Mindful movement exercises include yoga, tai chi, and qigong. Meditative practices that do not include movement include progressive relaxation, mindfulness, meditation, and acceptance therapies. On average, both mindful movement exercise (eg, yoga) and multicomponent mindfulness-based interventions (eg, mindfulness-based cognitive therapy, mindfulness-based stress reduction [MBSR], and mindfulness-based relapse prevention) can be as effective as other active treatments for psychiatric disorders such as MDD, anxiety, and substance use disorders.36,37 MBSR specifically has been shown to increase empathy, self-control, self-compassion, relationship quality, mindfulness, and spirituality as well as decrease rumination in healthy older adults.38 This suggests that MBSR can help strengthen the 4 factors of resilience.
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