18 | June | 2024 | Living Well Study

Research led by Wen-Jui Han from New York University, USA, published on April 3, 2024, in the open-access journal PLOS ONE, explores the enduring health impacts of early career work patterns. The study investigates how the hours worked during young adulthood can shape health outcomes decades later. It adopts a life-course perspective to examine the link between employment patterns and health in middle age. It uses data from The National Longitudinal Survey of Youth-1979 (NLSY79), which covers over 30 years and includes more than 7,000 individuals in the US.

The study reveals that a significant proportion of participants (26%) consistently adhered to stable standard work hours throughout their careers, while another third (35%) predominantly maintained traditional daytime schedules. In contrast, 17% started with standard hours in their 20s but later shifted to volatile work patterns involving evening, night, and variable hours. Additionally, 12% began with standard hours but transitioned to variable schedules later, and a final 10% experienced primary unemployment during this period.

Compared to those who predominantly worked traditional daytime hours throughout their careers, individuals with more volatile work schedules reported poorer sleep quality, shorter sleep duration, and a higher incidence of depressive symptoms by age 50. Particularly notable were the findings concerning individuals who maintained stable work hours in their 20s but transitioned to volatile schedules in their 30s, significantly impacting health outcomes similar to those observed in individuals with lower educational attainment.

Han’s research also highlights significant racial and gender disparities in work schedules and subsequent health outcomes. For instance, Black Americans were more likely to have volatile work schedules associated with poorer health outcomes, underscoring how certain demographic groups may disproportionately bear the negative consequences of such employment patterns.

The study suggests that volatile work schedules contribute to poor sleep quality, physical fatigue, and emotional exhaustion, rendering individuals more susceptible to an unhealthy lifestyle. Moreover, it indicates that the health effects of work schedules can accumulate over a lifetime, exacerbating societal health inequities.

Han emphasises that work, traditionally viewed as a means to secure resources for a decent life, has now become a health vulnerability due to increasing precariousness in work arrangements in an increasingly unequal society. Vulnerable social groups, such as women, Black individuals, and those with lower educational attainment, disproportionately experience the adverse health consequences associated with volatile work schedules.

More information: Wen-Jui Han et al, How our longitudinal employment patterns might shape our health as we approach middle adulthood—US NLSY79 cohort, PLoS ONE. DOI: 10.1371/journal.pone.0300245

Journal information: PLoS ONE Provided by PLOS

Everyone undergoes the ageing process uniquely, influenced by genetics, lifestyle, and environment. Some individuals achieve exceptional longevity, reaching their 90s or even 100s in robust health without needing medications or suffering from brain diseases. But what mechanisms enable these individuals to maintain their health as they age?

Luuk de Vries, along with colleagues Dick Swaab and Inge Huitinga from Joost Verhaagen’s group, delved into brains donated to the Netherlands Brain Bank for insights. This institution houses brain tissue from over 5,000 deceased donors with a diverse array of brain diseases, making it uniquely valuable due to its comprehensive medical histories and detailed disease courses documented alongside precise neuropathological diagnoses.

Within this repository, the researchers identified a remarkable subgroup: individuals who harboured Alzheimer’s disease pathology in their brains but exhibited no clinical symptoms during their lifetime—a cohort dubbed the ‘resilient’ group. The existence of such individuals raises profound questions about the underlying mechanisms that shield them from cognitive decline when others succumb.

Luuk de Vries explains, “The molecular and cellular processes at play in these resilient individuals remain unclear. We specifically sought donors with brain abnormalities indicative of Alzheimer’s yet who did not manifest cognitive decline. We identified 12 such donors, underscoring the rarity of this phenomenon. While we suspect genetics and lifestyle play pivotal roles in resilience, the precise mechanisms elude us.”

The findings suggest that maintaining an active lifestyle, engaging in cognitive challenges, and fostering robust social connections may help delay Alzheimer’s onset. Recent research also indicates that individuals involved in cognitively demanding tasks, such as complex jobs, may accumulate more Alzheimer’s pathology before symptoms emerge. Unravelling the molecular basis of resilience could unlock new avenues for developing medications that activate processes associated with resilience in Alzheimer’s patients.

Comparing the Alzheimer’s patients with the resilient group, the researchers observed distinct gene expression patterns. Notably, astrocytes—crucial brain cells with roles akin to garbage collectors and protective shields—appeared to produce higher levels of the antioxidant metallothionein in resilient individuals. Additionally, a microglia pathway commonly implicated in Alzheimer’s pathology seemed less active in the resilient group, potentially mitigating inflammation. Furthermore, the ‘unfolded protein response’, vital for clearing toxic misfolded proteins in brain cells, showed abnormalities in Alzheimer’s patients but remained relatively normal in resilient individuals. Moreover, there were indications of increased mitochondrial density in brain cells of resilient individuals, suggesting enhanced energy production capabilities.

However, the significance of these observed differences in cellular processes remains unclear—whether they represent causes or effects of resilience against Alzheimer’s disease. As Luuk de Vries notes, “Determining which processes initiate the disease progression is challenging with human data alone. Experimental manipulations in cellular or animal models are necessary to establish causality.” This critical step is now at the forefront of their research agenda.

Understanding why some individuals evade Alzheimer’s symptoms despite possessing brain pathology holds profound implications for future therapeutic strategies. By deciphering the mechanisms underpinning resilience, researchers aim to pave the way for novel treatments that could potentially activate resilience-promoting processes in Alzheimer’s patients, offering hope for mitigating the devastating effects of this neurodegenerative disease.

More information: Luuk E. de Vries et al, Gene-expression profiling of individuals resilient to Alzheimer’s disease reveals higher expression of genes related to metallothionein and mitochondrial processes and no changes in the unfolded protein response, Acta Neuropathologica Communications. DOI: 10.1186/s40478-024-01760-9

Journal information: Acta Neuropathologica Communications Provided by Netherlands Institute for Neuroscience