Aging & Longevity

CONCLUSIONS: The OAC-D identified five unique domains of depression, only one of which overlapped with DSM criteria. It demonstrated robust psychometric properties, providing a nuanced alternative to DSM-based measures and addressing the distinctive psychological challenges of cancer and aging.

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The potential of proteomic aging clocks for obesity research, and the extent of nonlinearity in longitudinal associations between body weight and biological aging, remain underexplored. We investigated how BMI at ages 18 and ~60, as well as changes in BMI from age 18 to ~60, relate to downstream epigenetic and proteomic aging. We also examined nonlinearity and interactions in these associations. Analyses were conducted in 401 Finnish twins with up to nine self-reported or measured BMI values...

CONCLUSION: These findings place mitochondrial proteome collapse at the center of aging and AD-seeded pathology, distinguish Aβ- and Tau-driven proteotoxic routes, and nominate a conserved panel of aggregation-prone proteins as mechanistic drivers and candidate biomarkers for early detection and intervention in AD.

Blood-brain barrier (BBB) dysfunction is a hallmark of many diseases of the brain, including those that represent the largest healthcare burden (for example, Alzheimer disease and stroke). Despite this, rejuvenation and repair of the BBB is not a mainstream concept. During life, the BBB is subjected to perturbations and stresses from a wide range of endogenous or exogenous sources, which can promote brain health or can lead to brain pathologies. The BBB supports many functions that are critical...

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Spatiotemporal changes in the nuclear lamina and cell metabolism shape cell fate, yet their interplay is poorly understood. Here we identify lamin A/C as a key regulator of cysteine catabolic flux essential for proper cell fate and longevity. Its loss in naive mouse pluripotent stem cells leads to upregulation of the cysteine-generating and catabolizing enzymes, cystathionine γ-lyase (CTH) and cystathionine β-synthase (CBS), thereby promoting de novo cysteine synthesis. Increased cysteine flux...

Integrated circuits for communications play an enabling role when it comes to outer-space exploration thanks to their small footprint and low weight^(1-3). However, owing to the severe irradiation effects of space energetic particles, the implementation of radiation-tolerant electronic circuits remains a challenge^(4-6). Here we report the observation of the space radiation effect on a satellite-based device and find that atomically thin materials are expected to accumulate minimal...

CONCLUSION: This claims-based frailty prediction model showed reasonable performance and prognostic value. It may support efficient, population-level frailty screenings where questionnaire-based assessments are impractical.

Serial multi-omic analysis of proteome, phosphoproteome, and glycoproteome is pivotal for elucidating drug mechanisms, discovering biomarkers, and identifying therapeutic targets. However, simultaneous multi-level post-translational modifications (PTMs) analysis via parallel processing is hampered by laborious, time-consuming procedures and inconsistent reproducibility. We present an integrated Multi-level PTMs-Proteomic Enrichment platform (MuPPE), enabling sequential glycoproteome,...

Environmental differences in genetic effect sizes, namely, gene-environment interactions, may uncover the genetic encoding of phenotypic plasticity^(1-3). We provide a cross-population atlas of gene-environment interactions comprising 440,210 individuals from European and Japanese populations, with replication in 539,794 individuals from diverse populations. By decomposing the contributions from age, sex and lifestyles, we delineate the aetiology of these gene-environment interactions, including...

Heart disease is the leading cause of death in the elderly population. Age-related heart failure is frequently associated with energy deficits in cardiomyocytes. These cells rely on their abundant, cristae-rich mitochondria for ATP production. ATP synthase, localized along the cristae rims, is central to this process. It is presumed that its function is tightly bound to its spatial organization, but details remain unclear. Here, we explored the spatiotemporal organization of ATP synthase in...

Aging is a dominant risk factor for chronic diseases characterized by the functional decline of tissues and organs. During aging, the hematopoietic system declines in regenerative capacity-seemingly attributable to increases in DNA damage, replicative stress, and autophagic flux-resulting in skewing towards a myeloid lineage and away from a lymphoid lineage. Here, we characterized the transcriptomic and cellular landscape of the aged C57Bl/6J mouse hematopoietic system using a combination of...

Humans routinely anticipate upcoming language, but whether such predictions come at a cognitive cost remains debated. In this study, we demonstrate the resource-dependent nature of predictive mechanisms in language comprehension across the lifespan: Experimentally limiting executive resources through a concurrent task reduces the effect of language predictability on reading time. Participants (N = 175, replication N = 96) read short articles presented word-by-word while completing a secondary...

Ribosomes are central to protein synthesis in all organisms. In mammals, the ribosome functional core is highly conserved. Remarkably, two rodent species, the naked mole-rat (NMR) and tuco-tuco, display fragmented 28S ribosomal RNA (rRNA), coupled with high translational fidelity and long lifespan. The unusual ribosomal architecture in the NMR and tuco-tuco has been speculated to be linked to high translational fidelity. Here, we show, by single-particle cryo-electron microscopy, that despite...

Phenotypic age, an aging indicator derived from clinical biomarkers, is associated with morbidities and mortality. However, a liver-specific phenotypic aging indicator is still lacking, and its longitudinal associations with liver-related outcomes, as well as the underlying biological mechanisms, remain elusive. We developed a liver-specific phenotypic age using 11 selected clinical blood markers within the England-White cohort of the UK Biobank and validated this metric in both the...

Mitochondrial function is important to healthy aging, as it influences energy metabolism, oxidative stress, and physical performance. With age, mitochondrial function and biosynthesis of coenzyme Q10 (CoQ10) may change. CoQ10 serves as a key antioxidant and component of the electron transport system. Supplementation with CoQ10 may help preserve mitochondrial function and support healthy aging. Forty older community-dwelling adults (74 ± 4 years) received either daily oral CoQ10 supplementation...

Age-related hearing loss (ARHL) is one of the most common causes of disability in older adults. It is also frequently associated with neurological and neurodegenerative disorders, including dementia, as well as with stress, anxiety, depression, and social isolation. These observations suggest that ARHL should be considered not merely as a sensory dysfunction, but rather as a complex disease involving extra-auditory domains. Namely, identifying shared pathogenic determinants between hearing loss...

INTRODUCTION: Age-related changes in brain signal complexity are associated with cognitive decline and reduced neural adaptivity in older adults. Exergaming offers a promising prophylactic intervention combining physical and cognitive training. The aim of the present study was to assess how exergaming alters the temporal trajectory of brain signal complexity at rest and during gameplay in older adults.

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