Aging & Longevity

CONCLUSION: Lower heel eBMD is independently associated with increased dementia risk among older adults.

Microglia are the brain's resident immune cells known for their dynamic responses to tissue and vascular injury. However, few studies have explored how microglial activity differs across the life stages of early development, adulthood, and aging. Using two-photon live imaging, we confirm that microglia in the adult cerebral cortex exhibit highly ramified processes and relatively immobile somata under basal conditions. Their responses to focal laser-induced injury occur over minutes and are...

Vacuolar acidification is crucial for the homeostasis of intracellular pH and the recycling of proteins and nutrients in cells, thereby playing important roles in various physiological processes related to vacuolar function. The key factors regulating vacuolar acidification and underlying mechanisms remain unclear. Here, we report that Arabidopsis phospholipase Dζ2 (PLDζ2) promotes the acidification of the vacuolar lumen to stimulate autophagic degradation under phosphorus deficiency. The pldζ2...

Training has emerged as a promising materials design technique in which function can be achieved through repeated physical modification of an existing material rather than by direct chemical functionalization, cutting, or reprocessing. This work investigates both the ability to train for function and then to erase that function on-demand in macroscopic metamaterials made from liquid crystal elastomers. We first show that the Poisson's ratio of these disordered arrays can be tuned via directed...

Aging induces substantial structural and functional decline in the retina, yet the molecular drivers of this process remain elusive. In this study, we used heterochronic parabiosis (HP) combined with single-cell RNA sequencing to generate comprehensive transcriptomic profiles of murine retinas from young, aged, and HP pairs, aiming to identify antiaging targets. Our analysis revealed extensive transcriptional alterations across retinal cell types with aging. HP experiments demonstrated that...

Age-dependent changes in DNA methylation allow chronological and biological age inference, but the underlying mechanisms remain unclear. Using ultra-deep sequencing of >300 blood samples from healthy individuals, we show that age-dependent methylation changes occur regionally across clusters of CpG sites either stochastically or in a coordinated block-like manner. Deep learning of single-molecule patterns from two genomic loci predicts chronological age with a median accuracy of 1.36-1.7 years...

Cellular senescence plays a dual role in tissue biology by promoting tumor suppression and wound healing when transient but driving inflammation, fibrosis, and age-related disease when persistent. The growing recognition that senescent cell clearance can reverse these pathologies has catalyzed efforts to develop therapeutics that preferentially kill senescent cells (also known as "senolytics"). However, clinical translation from bench to bedside remains challenging due to senescent state...

Across species, the "pace of life"-encompassing development, reproduction, and senescence-varies widely, yet the molecular mechanisms that regulate these interspecies trajectories of aging remain elusive. Even among vertebrates, a 1000-fold difference in life span is observed between species, ranging from several months in the turquoise killifish to half a millennium in the Greenland shark. As a relatively "young" area of investigation, aging research lacks the unifying conceptual frameworks...

Circulating Growth Differentiation Factors 11 and 8 (GDF11/8) exist in both latent and active forms, and it is unclear if specific forms can predict disease outcomes. Our data suggest that a dual-specific aptamer selectively binds GDF11/8 after prodomain activation. In 11,609 patients at risk for future cardiovascular events, low dual-specific aptamer-detected GDF11/8 levels strongly predicted adverse outcomes, including cardiovascular events (HR = 0.43, p = 9.1 × 10⁻⁶³) and all-cause mortality...

The pursuit of understanding early genetic or protein markers for ovarian aging has garnered considerable attention in the realm of reproductive medicine. Sirtuins (SIRTs) are a group of proteins that are NAD^(+)-dependent, and thanks to their properties, they are able to change the acetylation profile of proteins and post-translationally modify their functions, too. Previous research provided evidence that SIRTs influence fibrosis levels in several organs. With regard to ovaries, fibrosis is...

Metabolic cues are crucial for regulating haematopoietic stem and progenitor cells (HSPCs). However, the metabolic profile of human HSPCs remains poorly understood due to the limited number of cells and the scarcity of bone marrow samples. Here we present the integrated metabolome, lipidome and transcriptome of human adult HSPCs (lineage^(-), CD34^(+), CD38^(-)) upon differentiation, ageing and acute myeloid leukaemia. The combination of low-input targeted metabolomics with our newly optimized...

Singapore's rapidly aging population and increasing healthcare demands highlight the need for projections to inform policy planning. Here we adapted a previously published dynamic Markov microsimulation model, the Future Elderly Model, to estimate disease trajectories and healthcare expenditure among adults aged 51 years and older in Singapore. The model simulated four long-term lifestyle interventions aligned with the Healthier SG program from 2020 to 2050. Our projections indicate an...

Aging is associated with the accumulation of molecular damage, functional decline, increasing disease prevalence, and ultimately mortality. Although our system-wide understanding of aging has significantly progressed at the genomic and transcriptomic levels, the availability of large-scale proteomic datasets remains limited. To address this gap, we have conducted an unbiased quantitative proteomic analysis in male C57BL/6J mice, examining eight key organs (brain, heart, lung, liver, kidney,...

More than 57 million people globally suffer from neurodegenerative diseases, a figure expected to double every 20 years. Despite this growing burden, there are currently no cures, and treatment options remain limited due to disease heterogeneity, prolonged preclinical and prodromal phases, poor understanding of disease mechanisms, and diagnostic challenges. Identifying novel biomarkers is crucial for improving early detection, prognosis, staging and subtyping of these conditions....

The brain barrier system, including the choroid plexus, meninges and brain vasculature, regulates substrate transport and maintains differential protein concentrations between blood and cerebrospinal fluid (CSF). Aging and neurodegeneration disrupt brain barrier function, but proteomic studies of the effects on blood-CSF protein balance are limited. Here we used SomaScan proteomics to characterize paired CSF and plasma samples from 2,171 healthy or cognitively impaired older individuals from...

Aortic stenosis (AS) is the most prevalent valve disease in developed countries, with its incidence rising in the aging population. The current criteria for aortic valve replacement (AVR) are based on subjective symptoms and left ventricular ejection fraction (LVEF), which may not adequately reflect left ventricular (LV) dysfunction. This highlights the necessity for objective biomarkers to evaluate subclinical LV dysfunction. Serum angiotensin-converting enzyme 2 (sACE2) has emerged as a...

Nicotinamide riboside (NR) is a precursor to NAD^(+), a vital molecule for cellular energy metabolism whose levels decline with age. Aging is associated with loss of cognitive and immune function, alterations in hematological parameters, and increased vulnerability to stress. Although NR supplementation can mitigate age-related declines, it remains uncertain whether these positive effects persist when the organism is exposed to chronic physiological stress. We investigated this by exposing aged...

BACKGROUND: Frailty is a significant clinical syndrome affecting aging populations, leading to increased risks of negative outcomes such as falls, disability, hospitalization, and premature mortality. The concept has evolved from a simplistic view to a complex view that incorporates physical, psychological, cognitive, and social domains. Early intervention is crucial, yet research on the interactions among these domains is limited. This study protocol aims to outline various combinations of...

BACKGROUND: Frailty is the deterioration of physiological functions due to aging, linked to negative outcomes. Frailty, being a reversible and dynamic state, calls for individualized and comprehensive management. Goal Attainment Scaling (GAS) is a personalized method for establishing and assessing progress towards individual goals, suitable for older adults with complex requirements. We focus on attaining personalized intervention goals for elderly patients with frailty, correcting frailty...

During cognitive tasks, older adults often show increased frontoparietal neural activity and functional connectivity. Cognitive reserve accrued from positive life choices like long-term musical training can provide additional neural resources to help cope with the effect of aging. However, the relationship between cognitive reserve and upregulated neural activity in older adults remains poorly understood. In this study, we measured brain activity using functional magnetic resonance imaging...