Aging & Longevity

Frailty is an established benchmark of aging-related decline, yet most measures of frailty focus on physical decline. Increasing evidence that social environments influence trajectories of aging has led to growing interest in social frailty. Recently, a 10-item Social Frailty Index (SFI-10) was developed using data from the Health and Retirement Study (HRS) that used 8 social items plus chronological age and sex to predict mortality. This study evaluates the validity of the SFI-10, providing...

Interorgan communication is essential for metabolic homeostasis and healthy aging, with adipose tissue acting as a central hub that coordinates systemic metabolism, stress responses, and longevity. Here, we show that the miRNA-processing enzyme Dicer-1 (Dcr-1) acts in the fat body (FB) to regulate Dilp2 secretion from brain insulin-producing cells (IPCs), thereby modulating systemic insulin signaling and lifespan in Drosophila. Dcr-1 expression is reduced in multiple long-lived conditions, and...

Aging is a major contributor to the escalating prevalence of heart failure (HF). Ferroptosis has been implicated in age-related disorders and cardiovascular diseases. The role of ferroptosis in age-related HF remains unclear. Here, we show that aged rats exhibit impaired cardiac function accompanied by hallmark features of ferroptosis, including reduced glutathione peroxidase 4 (GPX4) expression and excessive lipid peroxidation. Consistently, cardiomyocyte-specific GPX4 knockout mice develop...

Cancer is associated with biological aging and functional decline; however, few studies have simultaneously examined objective changes in physical function and biological aging in older adults who develop cancer. We therefore compared functional and accelerated aging in generally healthy adults with and without incident invasive cancer, using data from DO-HEALTH, a three-year, randomized controlled trial including 2152 participants (mean age: 74.9 years, 61.1% women), free of major health...

Frailty is a modifiable aging-related condition driven by chronic inflammation and metabolic dysregulation, which are influenced by diet. Metabolomic profiling captures individual metabolic responses and can uncover mechanisms linking diet to frailty. This study examined the effects of food-derived metabolites on changes in frailty risk, both directly and through inflammatory pathways. This longitudinal study included baseline and three-year follow-up data from 9992 participants aged 45-85 years...

Older age combined with chronic disease increases the risk of malnutrition and frailty, impacting disease recovery and overall clinical outcomes. Serum concentrations of several trace elements and their respective biomarkers have not yet been investigated with regard to frailty in older adults with disease, although these patients most likely have an altered trace element profile owing to both inflammatory conditions and inadequate dietary intake. This cross-sectional study investigated trace...

Haematopoiesis has long been a paradigm for understanding how human genetic variation can influence physiology in health and disease, ranging from the genetic characterization of Mendelian blood diseases to population-scale genomic studies of blood cell phenotypes and diseases. More recently, advances in single-cell genomics and variant-to-function mapping are enabling mechanistic insights into how genetic variation shapes blood cell development. Alongside inherited variation, the...

How minute pathogenic signals trigger decisive immune responses is a fundamental question in biology. Classical signaling often relies on ATP-driven enzymatic cascades, but innate immunity frequently employs death fold domain (DFD) self-assembly. The energetic basis of this assembly is unknown. Here, we show that specific DFDs function as energy reservoirs through metastable supersaturation. Characterizing all 109 human DFDs, we identified sequence-encoded nucleation barriers specifically in the...

Age-related cellular changes negatively impact CD4^(+) T cell function. Our prior work showed that mitochondrial complex II (succinate dehydrogenase [SDH]) expression was upregulated in T cells from older (O) adults (60-80 years old). T cells from older adults also produced higher amounts of cytokines generally considered proinflammatory, such as Th17 cytokines IL-17A/F and IL-21, and the Th-17-supportive cytokine IL-6, compared to T cells from younger (Y) adults (25-40 years old). The objective...

No abstract

The question of whether aging should be classified as a disease has gained prominence in geroscience, fueled by advances in molecular biology and the aspiration to develop interventions that mitigate age-associated functional decline. However, evolutionary models describe aging as an emergent consequence of declining selection gradients and life-history trade-offs rather than as a deviation from species-typical function. Comparative data across taxa reveal substantial heterogeneity in aging...

Postural control is expressed as intermittent organization of center-of-pressure (CoP) motion on a saddle-shaped manifold typically aligned with the anteroposterior (AP) and mediolateral (ML) axes. When task demands reorient postural focus, this saddle rotates away from the AP-ML alignment yet preserves orthogonal axes that indicate directions of greatest and least fractal temporal correlations in sway. Preserved orthogonality appears to reflect a balance between endogenous fractal fluctuations...

The identification of functional ligand-membrane protein interactions under native conditions remains a major challenge in cancer biology. Using cell-systematic evolution of ligands by exponential enrichment, we identified a high-affinity DNA aptamer, CW06, against breast cancer cells. To precisely identify its native membrane target, we developed Aptamer-mediated Metabolic Glycan-labeling Proximity Hybridization (Apt-MGPH), which revealed the mitochondrial solute carrier SLC25A24 as the...

Through alternative splicing, the TP53 gene can generate multiple protein isoforms with distinct biochemical properties. The p53psi isoform has been identified as a shorter variant than full-length p53 as it lacks nuclear localization, oligomerization, and part of the DNA binding domains due to the use of an alternative 3' splice site in intron 6. Several TP53-truncating mutations, including those producing p53psi, have been detected in a significant proportion of human tumors. However, the...

CONCLUSIONS AND IMPLICATIONS: Despite methodological variation, community-based programs that reduce loneliness, social isolation, and support aging in place consistently generate positive SROI ratios, benefiting participants, families, and volunteers while reducing health care use. Collaboration among researchers, communities, and policymakers is essential to translate findings into community actions that enable older adults to age in place.

CONCLUSIONS AND IMPLICATIONS: Stable health trajectories are strongly linked to better cognitive outcomes, whereas sharp health declines predict poorer cognition. Our findings highlight the interconnected biological and behavioral pathways through which health changes may accelerate or mitigate cognitive deterioration, offering insights for targeted interventions and holistic care for persons with cognitive impairment.

DNA replication stress responses are guardians of genomic stability critical during development, hematopoiesis, cancer therapy response, aging and disease suppression. Central to these responses are reversed forks (RF), which are distinct four-way DNA structures formed during DNA replication stalling to protect against toxic DNA lesions. Historically, RF detection relies on specialized electron microscopy, precluding studies within their native cellular context. By harnessing intrinsic...

CONCLUSIONS: We propose that aging affects RFT performance through two dissociable mechanisms. A general decline in multisensory integration increases overall errors symmetrically across tilt angles. The clockwise-specific asymmetry, by contrast, may reflect age-related changes in lateralized visuospatial attention-specifically, the well-documented rightward attentional shift that accompanies healthy aging-which differentially affects the weighting of visual cues for clockwise vs....

Cognitive impairment associated with obstructive sleep apnea (OSA) is more prevalent and severe in the elderly, possibly due to age-related increases in neuronal susceptibility to intermittent hypoxia (IH). As telomere dysfunction is a key driver of cellular aging, this study aimed to characterize the interaction between telomere dysfunction and IH, and to explore the associated molecular alterations. Using telomere-damaged PC12 cells and G3 Tert^(-/-) progeria mice exposed to IH, we assessed...

OBJECTIVE: Cerebral microbleeds (CMBs) are small vascular lesions detectable on MRI and are associated with increased stroke risk and cognitive decline. However, imaging-based diagnosis is limited by cost and accessibility. This study aimed to identify serum protein biomarkers for early CMB diagnosis and to elucidate molecular mechanisms underlying CMB subtypes.