Aging & Longevity

Identifying neuroimaging markers of cognitive performance in healthy aging is challenging due to heterogeneity in brain and cognitive characteristics. Among the factors relevant to that heterogeneity are lifestyle choices, of which each individual factor explains only a very small amount of variance in brain and cognition. This challenges current approaches for the prediction of cognitive outcomes. We examined whether brain features associated with an overall lifestyle profile (BF-Life(multi))...

INTRODUCTION: The aging population increases type 2 diabetes mellitus (T2DM) prevalence and consequently heightens related complications, including dementia and microvascular disease. This study examined the relationship between diabetic retinopathy (DR) and cognitive decline in adults with T2DM.

Aging alters both brain structure and electrophysiology, which can be measured non-invasively by structural magnetic resonance imaging (MRI) and event-related potentials (ERPs). On average, gray matter declines steadily from early adulthood, whereas white matter increases into midlife before declining. With respect to ERPs, the well-established P300 response shows reduced amplitude and delayed latency from early adulthood onward. Few studies test whether structural MRI and ERP measures correlate...

Aging research has increasingly recognized the need for accurate biomarkers of aging, with aging clocks emerging as a powerful tool to quantify the degree of age-related biological change. However, broad clinical implementation and the establishment of wide use of these biomarkers of aging remain ongoing. Resilience reflects a dynamic property of physiological homeostasis and offers a complementary lens to functionally interpret aging. Resilience does not capture the ground state the biological...

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Aging reduces the quality and quantity of sleep, and sleep disruption is predictive of neurodegeneration and cognitive decline. Sleep loss could affect brain health through disruption of cerebrospinal fluid (CSF) circulation, which is important for brain homeostasis. In young adults, large CSF flow waves appear during non-rapid eye movement sleep; however, whether sleep-dependent brain fluid physiology changes in aging is not known. Here we imaged large-scale CSF flow and hemodynamics in young...

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Asymmetry on the left-right axis is an organizing principle of the human brain that is important for diverse cognitive and behavioural functions. Advances in neuroimage analysis, genomics and large-scale data collection in the past decade have transformed our understanding of the biological foundations and multivariate nature of brain asymmetry. In this Review, we synthesize evidence across scales - from functional and macro-anatomical asymmetries and their inter-relations to microstructural,...

Extraembryonic tissues and many cancers share unusual DNA methylation landscapes, but how these states arise remains unclear. Here, we use GATA6- and CDX2-driven reprogramming of mouse embryonic stem cells to track genome-wide epigenetic remodeling during acquisition of extraembryonic cell fates. Despite activating distinct transcriptional programs from non-overlapping genomic targets, both transcription factors trigger rapid and genomically synchronized convergence to cancer-like DNA...

Aging is a multifactorial process shaped by genetic, metabolic, and environmental factors. Yet one physical constant-gravity-has rarely been considered as a potential contributor to the aging process. This perspective explores the hypothesis that chronic exposure to Earth's gravity, through its lifelong hydrostatic effects on cerebral blood flow (CBF), may represent an unrecognized driver of systemic aging. The brain, particularly deep regulatory centers in the hypothalamus and brainstem,...

Cardiac aging is traditionally framed as a progressive loss of energetic capacity, yet accumulating evidence indicates that iron-dependent lipid peroxidation and ferroptotic susceptibility may contribute to age-related myocardial vulnerability. Here, we integrate evidence linking mitochondrial quality control, membrane lipid remodeling, antioxidant capacity, and iron handling to the emergence of a ferroptosis-permissive state in aging cardiomyocytes. We further propose that aerobic exercise may...

The ability to recover skeletal muscle after periods of disuse declines with age leading to persistent deficits in strength and function that extend beyond muscle mass loss. Here, we investigated whether age-related alterations in lipid remodeling contribute to impairment in skeletal muscle recovery following disuse. Lipidomic and oxylipin profiling revealed that aged mouse muscle is characterized by sustained phosphatidylcholine and omega-6-dependent COX-prostaglandin signaling during early...

Natural products derived from traditional medicines are valuable sources of potential geroprotective compounds; however, their translation into therapeutic candidates is limited by chemical complexity, polypharmacology, limited mechanistic resolution, and lengthy experimental validation. Artificial intelligence (AI) offers an emerging framework for integrating chemical, pharmacological, multi-omics, imaging, and literature derived data to accelerate natural product anti-aging research. This...

Continuum elastic shells with residual stresses can exhibit complex motions that require vanishing elastic energy to excite, also called geometric zero modes, enabling them to be driven by weak and generic energy inputs. Despite recent interest in these modes, we understand very little about their dynamical properties. Plates with a curved, rather than flat, in-plane geometry, also called non-Euclidean plates, are one example in which residual stresses and geometry combine to produce a continuum...

Meningiomas exhibit substantial molecular, anatomical, and microenvironmental heterogeneity, yet the spatial organization of their lipid biology remains poorly understood. Emerging lipidomic studies demonstrate extensive remodeling of membrane, signaling, and mitochondrial lipid classes, with profiles varying according to molecular genotype, histopathological grade, and potentially patient characteristics. In parallel, developmental, single-cell, and spatial studies have revealed the meninges...

BackgroundUnderstanding changes in long-term care (LTC) applicants' needs informs service planning.ObjectiveTo examine trends in functional impairment and multimorbidity among Hong Kong's publicly funded LTC applicants during 2001-2019.MethodsWe analyzed interRAI assessments from 315,556 applicants aged ≥60. Hierarchical mixed-effects models estimated trends in physical and cognitive impairment, loneliness, and multimorbidity, adjusting for age, birth cohort, and sociodemographic factors....

ObjectiveHispanic individuals are understudied in cognitive aging research and are disproportionately exposed to crime, yet the cognitive consequences of this exposure remain unclear. We examined whether county-level crime moderates the association between physical functioning (PF) and cognitive change among Mexican Americans aged 75 years and older without cognitive impairment at baseline.MethodsParticipants included 1,189 older adults from the Hispanic Established Populations for the...

Aging research has advanced along two largely parallel paths. Experimental biology has transformed aging research by establishing that aging is biologically malleable and identifying conserved molecular and cellular mechanisms that regulate lifespan and healthspan. In parallel, population research has revealed substantial heterogeneity in human aging and identified social, environmental, behavioral, and genetic factors associated with differences in aging trajectories. Despite a shared goal of...

Mild disruptions to mitochondrial function can lead to the activation of an adaptive program that extends animal lifespan. The mitochondrial unfolded protein response (UPRmt) is associated with such conditions that prolong lifespan. We previously discovered that methionine restriction, resulting from the genetic loss of methionine synthase in C. elegans, activated the UPRmt and extended lifespan. Here, we demonstrate that methionine restriction activates the UPRmt and delays aging within the...

Aging is a complex biological process often characterized by increased vulnerability to disease, infection, and death. This increased vulnerability is mechanistically linked to a progressive and functional decline of the immune system. In humans, aged T cells lose their ability to effectively surveil complex microenvironments, thereby decreasing their capacity to clear infections, eradicate diseases, and maintain physiological homeostasis. However, specific mechanisms by which aged T cells lose...