Both environmental exposures and genetics are known to play important roles in shaping human aging. Here we aimed to quantify the relative contributions of environment (referred to as the exposome) and genetics to aging and premature mortality. To systematically identify environmental exposures associated with aging in the UK Biobank, we first conducted an exposome-wide analysis of all-cause mortality (n = 492,567) and then assessed the associations of these exposures with a proteomic age clock (n = 45,441), identifying 25 independent exposures associated with mortality and proteomic aging. These exposures were also associated with incident age-related multimorbidity, aging biomarkers and major disease risk factors. Compared with information on age and sex, polygenic risk scores for 22 major diseases explained less than 2 percentage points of additional mortality variation, whereas the exposome explained an additional 17 percentage points. Polygenic risk explained a greater proportion of variation (10.3–26.2%) compared with the exposome for incidence of dementias and breast, prostate and colorectal cancers, whereas the exposome explained a greater proportion of variation (5.5–49.4%) compared with polygenic risk for incidence of diseases of the lung, heart and liver. Our findings provide a comprehensive map of the contributions of environment and genetics to mortality and incidence of common age-related diseases, suggesting that the exposome shapes distinct patterns of disease and mortality risk, irrespective of polygenic disease risk.

We aimed to assess the psychoeducational quality of TikTok content about attention-deficit/hyperactivity disorder (ADHD) from the perspective of both mental health professionals and young adults across two pre-registered studies. In Study 1, two clinical psychologists with expertise in ADHD evaluated the claims (accuracy, nuance, overall quality as psychoeducation material) made in the top 100 #ADHD TikTok videos. Despite the videos’ immense popularity (collectively amassing nearly half a billion views), fewer than 50% of the claims about ADHD symptoms were judged to align with the Diagnostic and Statistical Manual of Mental Disorders. In Study 2, 843 undergraduate students (no ADHD =  224, ADHD self-diagnosis =  421, ADHD formal diagnosis =  198) were asked about their typical frequency of viewing #ADHD content on TikTok and their perceptions of ADHD and were shown the top 5 and bottom 5 psychologist-rated videos from Study 1. A greater typical frequency of watching ADHD-related TikToks was linked to a greater willingness to recommend both the top and bottom-rated videos from Study 1, after controlling for demographics and ADHD diagnostic status. It was also linked to estimating a higher prevalence of ADHD in the general population and greater challenges faced by those with ADHD. Our findings highlight a discrepancy between mental health professionals and young adults regarding the psychoeducational value of #ADHD content on TikTok. Addressing this is crucial to improving access to treatment and enhancing support for those with ADHD.

Previous studies have suggested that systemic viral infections may increase risks of dementia. Whether this holds true for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infections is unknown. Determining this is important for anticipating the potential future incidence of dementia. To begin to do this, we measured plasma biomarkers linked to Alzheimer’s disease pathology in the UK Biobank before and after serology-confirmed SARS-CoV-2 infections. SARS-CoV-2 infection was associated with biomarkers associated with β-amyloid pathology: reduced plasma Aβ42:Aβ40 ratio and, in more vulnerable participants, lower plasma Aβ42 and higher plasma pTau-181. The plasma biomarker changes were greater in participants who had been hospitalized with COVID-19 or had reported hypertension previously. We showed that the changes in biomarkers were linked to brain structural imaging patterns associated with Alzheimer’s disease, lower cognitive test scores and poorer overall health evaluations. Our data from this post hoc case–control matched study thus provide observational biomarker evidence that SARS-CoV-2 infection can be associated with greater brain β-amyloid pathology in older adults. While these results do not establish causality, they suggest that SARS-CoV-2 (and possibly other systemic inflammatory diseases) may increase the risk of future Alzheimer’s disease.

While observational studies and small pilot trials suggest that vitamin D, omega-3 and exercise may slow biological aging, larger clinical trials testing these treatments individually or in combination are lacking. Here, we report the results of a post hoc analysis among 777 participants of the DO-HEALTH trial on the effect of vitamin D (2,000 IU per day) and/or omega-3 (1 g per day) and/or a home exercise program on four next-generation DNA methylation (DNAm) measures of biological aging (PhenoAge, GrimAge, GrimAge2 and DunedinPACE) over 3 years. Omega-3 alone slowed the DNAm clocks PhenoAge, GrimAge2 and DunedinPACE, and all three treatments had additive benefits on PhenoAge. Overall, from baseline to year 3, standardized effects ranged from 0.16 to 0.32 units (2.9–3.8 months). In summary, our trial indicates a small protective effect of omega-3 treatment on slowing biological aging over 3 years across several clocks, with an additive protective effect of omega-3, vitamin D and exercise based on PhenoAge.

Humans lack memories for specific events from the first few years of life. We investigated the mechanistic basis of this infantile amnesia by scanning the brains of awake infants with functional magnetic resonance imaging while they performed a subsequent memory task. Greater activity in the hippocampus during the viewing of previously unseen photographs was related to later memory-based looking behavior beginning around 1 year of age, suggesting that the capacity to encode individual memories comes online during infancy. The availability of encoding mechanisms for episodic memory during a period of human life that is later lost from our autobiographical record implies that postencoding mechanisms, whereby memories from infancy become inaccessible for retrieval, may be more responsible for infantile amnesia. Humans and many other species can form memories during infancy but cannot recall these memories later in life. Yates et al . investigated the mechanism mediating this so-called infantile amnesia using functional magnetic resonance imaging (fMRI) in awake infants performing a memory task (see the Perspective by Ramsaran and Frankland). They found that infants are capable of encoding memories during infancy, and deficits in postencoding retrieval mechanisms are likely responsible for infantile amnesia in humans. —Mattia Maroso

Abstract Introduction To estimate the effect of social media use in 14 year olds on risk of and inequalities in cigarette, e-cigarette, and dual use at 17 years, using the UK-representative Millennium Cohort Study (born 2000–2002). Aims and Methods The relationship of time spent on social media (using questionnaires [n = 8987] and time-use-diaries [n = 2520]) with cigarette, e-cigarette, and dual use was estimated using adjusted odds ratios (AORs) or relative risk ratios (ARRRs). Effect modification was examined (using parental education as an indicator for socioeconomic circumstances) by comparing adjusted risk differences within low and high-parental education groups. Analyses accounted for prespecified confounders (identified via directed acyclic graphs), baseline outcome measures (to address reverse causality), sample design, attrition, and item-missingness (through multiple imputation). Results Time spent on social media was associated with increased risk of cigarette, e-cigarette, and dual use in a dose–response manner. Social media use for ≥2 hours/day (vs. 1–<30 minutes) was associated with increased cigarette (AOR 2.76 [95% confidence interval 2.19 to 3.48]), e-cigarette (3.24 [2.59 to 4.05]), and dual use (ARRR 4.11 [2.77 to 6.08]). The risk of cigarette use among 30 minutes–<1 hour/day users (vs. non-users) were smaller in those with high versus low parental education (ARDs 1.4% vs. 12.4%). Similar findings were observed across the higher time categories. Analyses using time-use-diaries, in complete case samples, and with additional adjustment for baseline outcome measures generally revealed similar findings. Conclusions After accounting for observed confounders and potential reverse causality, findings suggest social media use increases the risk of cigarette, e-cigarette, and dual use in a dose–response manner. Guidance addressing adolescent online safety should be prioritized. Implications This study’s identification of a dose–response relationship and differential effects across socioeconomic groups, could assist in the development of guidance on time spent on social media. The adverse effects of social media use on adolescent cigarette, e-cigarette, and dual use supports legislation aimed at promoting adolescent online safety. Study findings strengthen calls to prohibit social media marketing of nicotine-related products and importantly highlight the need to increase awareness and understanding of the underlying algorithms which drive adolescent exposure to nicotine-related content on social media to ensure they are functioning in a way that best serves the adolescent population.

The biology underlying the connection between social relationships and health is largely unknown. Here, leveraging data from 42,062 participants across 2,920 plasma proteins in the UK Biobank, we characterized the proteomic signatures of social isolation and loneliness through proteome-wide association study and protein co-expression network analysis. Proteins linked to these constructs were implicated in inflammation, antiviral responses and complement systems. More than half of these proteins were prospectively linked to cardiovascular disease, type 2 diabetes, stroke and mortality during a 14 year follow-up. Moreover, Mendelian randomization (MR) analysis suggested causal relationships from loneliness to five proteins, with two proteins (ADM and ASGR1) further supported by colocalization. These MR-identified proteins (GFRA1, ADM, FABP4, TNFRSF10A and ASGR1) exhibited broad associations with other blood biomarkers, as well as volumes in brain regions involved in interoception and emotional and social processes. Finally, the MR-identified proteins partly mediated the relationship between loneliness and cardiovascular diseases, stroke and mortality. The exploration of the peripheral physiology through which social relationships influence morbidity and mortality is timely and has potential implications for public health.