How Healthy
Cohort mortality forecasts indicate signs of deceleration in life expectancy gains
José Andrade, Carlo Giovanni Camarda & Héctor Pifarré i Arolas
Proceedings of the National Academy of Sciences, 2 September 2025
Abstract:
The fast-paced improvements in mortality in high-income countries since the early 1900s have led to a sustained increase in life expectancy. However, whether this linear trend will continue or life expectancy gains will decelerate in the near future remains unclear. To answer this question, we apply multiple established and recently developed mortality forecasting methods to estimate cohort life expectancy for individuals born between 1939 and 2000 in 23 high-income countries. Across all forecasting methods, our results robustly and consistently indicate a deceleration in cohort life expectancy. The previously observed pace of improvement, 0.46 y per cohort, declines by 37% to 52%, depending on the method used. Robustness checks suggest that these findings are unlikely to be solely due to downward bias in cohort life expectancy forecasts. Furthermore, an age-decomposition analysis indicates that this deceleration is primarily driven by a slower pace of mortality improvement at very young ages. Over half of the total deceleration is attributable to mortality trends under age 5, while more than two-thirds is explained by mortality trends under age 20. This pattern had already emerged in the observed data for the cohorts included in our analysis. Thus, even if these estimates turned out to be overly pessimistic, it is unlikely that the deceleration will reverse in the near future.
In Money, We Survive: The Effects of Social Security Retirement Income on Longevity
Hamid Noghanibehambari & Jason Fletcher
NBER Working Paper, September 2025
Abstract:
An old and debated line of research examines the income-mortality relationship and finds mixed evidence. In this paper, we re-evaluate previous studies using a new dataset and implementing a difference-in-difference model based on a Notch in Social Security retirement benefits to overcome selection and endogeneity issues. We employ Social Security Administration death records and find a positive income-longevity relationship. Moreover, we find more pronounced effects among low-educated individuals and people from low socioeconomic status families. Analyses using census data suggest that part of the reductions in retirement income are offset by wage income due to post-retirement labor force participation. Past age 80, the net adverse effects of the policy on both income and longevity become more pronounced.
Lithium deficiency and the onset of Alzheimer’s disease
Liviu Aron et al.
Nature, 18 September 2025, Pages 712-721
Abstract:
The earliest molecular changes in Alzheimer’s disease (AD) are poorly understood. Here we show that endogenous lithium (Li) is dynamically regulated in the brain and contributes to cognitive preservation during ageing. Of the metals we analysed, Li was the only one that was significantly reduced in the brain in individuals with mild cognitive impairment (MCI), a precursor to AD. Li bioavailability was further reduced in AD by amyloid sequestration. We explored the role of endogenous Li in the brain by depleting it from the diet of wild-type and AD mouse models. Reducing endogenous cortical Li by approximately 50% markedly increased the deposition of amyloid-β and the accumulation of phospho-tau, and led to pro-inflammatory microglial activation, the loss of synapses, axons and myelin, and accelerated cognitive decline. These effects were mediated, at least in part, through activation of the kinase GSK3β. Single-nucleus RNA-seq showed that Li deficiency gives rise to transcriptome changes in multiple brain cell types that overlap with transcriptome changes in AD. Replacement therapy with lithium orotate, which is a Li salt with reduced amyloid binding, prevents pathological changes and memory loss in AD mouse models and ageing wild-type mice. These findings reveal physiological effects of endogenous Li in the brain and indicate that disruption of Li homeostasis may be an early event in the pathogenesis of AD. Li replacement with amyloid-evading salts is a potential approach to the prevention and treatment of AD.
Polygenic scores for depression are associated with indices of neighborhood adversity
Cope Feurer et al.
Journal of Psychopathology and Clinical Science, October 2025, Pages 722-732
Abstract:
Genome-wide association studies have allowed for the creation of polygenic scores (PGSs) reflecting genetic liability for depression, yet recent work suggests that these PGSs may also reflect greater genetic propensity toward higher levels of stress exposure. The current study sought to extend prior findings to examine whether an established depression PGS (DEP-PGS) is associated with greater stress exposure at the neighborhood level in a sample of preadolescent children. This study included 278 children of European ancestry between the ages of 7 and 11 (45.3% female) and their parents. Parents and children completed clinical interviews and questionnaires, and children provided genetic samples. Children’s neighborhoods were defined based on their current home address, and geocoded indices of neighborhood adversity (i.e., area socioeconomic disadvantage, crime, and opportunity) were matched to zip codes. As hypothesized, children with greater genetic liability for depression, as reflected by DEP-PGSs, were more likely to live in neighborhoods characterized by greater adversity. Findings were maintained when statistically controlling for family socioeconomic status and parents’ and children’s histories of depression and anxiety. The current findings build upon prior research highlighting depression-relevant gene–environment correlations and extend this work to provide evidence that DEP-PGSs may capture genetic liability for exposure to stressful contexts at the neighborhood level. Future research is needed to replicate findings in diverse samples and to examine whether neighborhood-level adversity mediates the relation between DEP-PGSs and future depression risk in youth.
Cigarette Purchasing Behaviors and Financial Burden of Cigarette Spending after a Major Tobacco Tax Increase in California: Evidence from Household Panel Data
Dian Gu et al.
University of California Working Paper, August 2025
Objectives: To examine the patterns of cigarette purchasing behaviors and financial burden of cigarette spending among California households following the implementation of California Proposition 56, which increased cigarette excise taxes by $2-per-pack on April 1, 2017.
Methods: Using longitudinal NielsenIQ Consumer Panel data, we identified a cohort of 2,324 California households that participated continuously from 2016 through 2022. The outcomes included cigarette purchasing behaviors and financial burden of cigarette spending. We compared outcomes from the 2016 baseline to each follow-up year and to the 5-year average for 2018–2022 (post-implementation), both overall and by income group.
Results: In 2016, 10.6% of California households purchased cigarettes. This percentage decreased steadily over time to 4.2% in 2022 (p<.001). However, the reduction over the 5-year period was significantly smaller among low-income households compared to middle-income (2.1% vs. 5.1%, p = 0.004) and high-income groups (2.1% vs. 3.8%, p < .001). Among low-income households, the annual cigarette spending increased significantly from $651 at baseline to $1,053 in 2021 (p=0.043) and $1,343 in 2022 (p = 0.002). Changes in the annual quantity of cigarette packs purchased and proportion of income spent on cigarettes were mostly not statistically significant.
Repeated head trauma causes neuron loss and inflammation in young athletes
Morgane Butler et al.
Nature, forthcoming
Abstract:
Repetitive head impacts (RHIs) sustained from contact sports are the largest risk factor for chronic traumatic encephalopathy (CTE). Currently, CTE can only be diagnosed after death and the events that trigger initial hyperphosphorylated tau (p-tau) deposition remain unclear. Furthermore, the symptoms endorsed by young individuals are not fully explained by the extent of p-tau deposition, severely hampering therapeutic interventions. Here we observed a multicellular response prior to the onset of CTE p-tau pathology that correlates with number of years of RHI exposure in young people (less than 51 years of age) with RHI exposure, the majority of whom played American football. Leveraging single-nucleus RNA sequencing of tissue from 8 control individuals, 9 RHI-exposed individuals and 11 individuals with low-stage CTE, we identify SPP1-expressing inflammatory microglia, angiogenic and inflamed endothelial cells, astrocytosis and altered synaptic gene expression in those exposed to RHI. We also observe a significant loss of cortical sulcus layer 2/3 neurons independent of p-tau pathology. Finally, we identify TGFβ1 as a potential signal that mediates microglia–endothelial cell cross talk. These results provide robust evidence that multiple years of RHI is sufficient to induce lasting cellular alterations that may underlie p-tau deposition and help explain the early pathogenesis in young former contact sport athletes. Furthermore, these data identify specific cellular responses to RHI that may direct future identification of diagnostic and therapeutic strategies for CTE.
Early-life infectious disease exposure, the “hygiene hypothesis,” and lifespan: Evidence from hookworm disease
Ralph Lawton
Proceedings of the National Academy of Sciences, 2 September 2025
Abstract:
Exposure to infectious disease in early life may have long-term ramifications for health and lifespan. However, reducing pathogen exposure may not be uniformly beneficial. The rise of modern sanitation and reduction of infectious diseases has been implicated in increasing levels of allergy and immune dysregulation: termed, the “hygiene hypothesis.” This study leverages quasi-experimental variation from combining precampaign hookworm exposure with the Rockefeller Sanitary Commission’s deworming campaign in the early 20th century to rigorously examine the impacts of childhood hookworm exposure on adult lifespan and morbidity. Findings show deworming before age five leads to 2.5 additional months of life in a large sample of adult death records. Further, decreasing hookworm exposure is related to improvements in biomarkers for inflammation and skin-tested allergies, in contrast to predictions of the “hygiene hypothesis.” Placebo tests using health outcomes that should not be affected by deworming do not show similar patterns. Overall, childhood deworming leads to improvements in morbidity and lifespan decades later.
Local Problems, Local Solutions: Evidence from the Drug-Free Communities Program on Youth Development
Shijun You, Wei Fu & Shin-Yi Chou
NBER Working Paper, August 2025
Abstract:
The Drug-Free Communities (DFC) Support Program aims to reduce youth substance use by fostering multi-sector collaboration and implementing locally tailored strategies within the community. This study is among the first to evaluate the program’s impact on youth development outcomes in the United States. Using the Callaway and Sant’Anna (2021) difference-in-differences (CSDID) estimator, we find that the DFC program significantly reduces drug-related juvenile crime and improves academic performance. The effects are particularly pronounced in communities where coalitions include government agencies, highlighting the critical role of institutional coordination in mobilizing local resources. We also explore behavioral mechanisms, documenting reductions in marijuana use and opioid-related inpatient hospitalizations. A cost-benefit analysis indicates substantial welfare gains, suggesting that early-life prevention represents a cost-effective investment in public health.
Does SNAP participation increase bulk purchases?
Hannah Wich & Katherine Harris-Lagoudakis
Journal of Public Economics, September 2025
Abstract:
The Supplemental Nutrition Assistance Program (SNAP) issues monthly lump-sum payments. One potential benefit of SNAP payments is that they could ease liquidity constraints for participating households. Using novel retailer panel data, this is the first study to investigate the effect of SNAP on bulk purchasing behavior using within-household variation. To estimate a causal relationship between SNAP and bulk purchases, we use the timing of program re-certification as a source of exogenous variation in the decision to participate in SNAP. We find that participating in SNAP increases the expenditure share of bulk purchases for all groceries by six percentage points. Analyses aiming to disentangle whether increased bulk spending among SNAP households reflects an “income effect” or a “liquidity effect” point to the former, with spending patterns indicating “splurge behavior” rather than efforts to minimize prices.
Respiratory viral infections awaken metastatic breast cancer cells in lungs
Shi Chia et al.
Nature, 11 September 2025, Pages 496-506
Abstract:
Breast cancer is the second most common cancer globally, with most deaths caused by metastatic disease, often following long periods of clinical dormancy. Understanding the mechanisms that disrupt the quiescence of dormant disseminated cancer cells (DCCs) is crucial for addressing metastatic progression. Infections caused by respiratory viruses such as influenza and SARS-CoV-2 trigger both local and systemic inflammation. Here we demonstrate, in mice, that influenza and SARS-CoV-2 infections lead to loss of the pro-dormancy phenotype in breast DCCs in the lung, causing DCC proliferation within days of infection and a massive expansion of carcinoma cells into metastatic lesions within two weeks. These phenotypic transitions and expansions are interleukin-6 dependent. We show that DCCs impair lung T cell activation and that CD4+ T cells sustain the pulmonary metastatic burden after the influenza infection by inhibiting CD8+ T cell activation and cytotoxicity. Crucially, these experimental findings align with human observational data. Analyses of cancer survivors from the UK Biobank (all cancers) and Flatiron Health (breast cancer) databases reveal that SARS-CoV-2 infection substantially increases the risk of cancer-related mortality and lung metastasis compared with uninfected cancer survivors. These discoveries underscore the huge impact of respiratory viral infections on metastatic cancer resurgence, offering new insights into the connection between infectious diseases and cancer metastasis.