Aging & Longevity

The nervous system is primarily composed of neurons and glia, and the communication between them has profound roles in regulating the development and function of the brain. Neuron-glia signal transduction is known to be mediated by secreted signals through ligand-receptor interactions on the cell membrane. Here we show a new mechanism for neuron-glia signal transduction, wherein neurons transmit proteins to glia through extracellular vesicles, activating glial signaling pathways. We find that in...

Aging biomarkers that predict age given methylomic data are referred to as epigenetic aging clocks. While the earliest, first-generation clocks were exclusively trained to predict chronological age, more recent next-generation models have been explicitly trained to associate with health, lifestyle, and/or age-related outcomes. Although these next-generation models have been trained using distinct approaches and techniques, existing evidence indicates that they associate with a greater number of...

ObjectiveTo identify subgroups of midlife and older adults from the United States (US), defined by specific combinations of factors, who are more or less likely to meet age-specific sleep duration recommendations.MethodsParticipants (n = 3,124) aged ≥ 40 years were drawn from the 2011-2018 National Health and Nutrition Examination Survey cycles. The primary outcome was meeting age-specific sleep duration recommendations (7 to 9 hours per night) to promote optimal health. Signal detection...

CONCLUSIONS: Older adults with both VI and poor mobility are at an additive increased risk of mortality. Future interventions may want to target older adults with both VI and poor mobility to improve survival.

The varying incidence of aging-related diseases and the gender gap in life expectancy suggest differences in the aging process between the sexes. Yet, little is known about sex-specific differences in genomic instability, a key factor in aging. Here, we analyzed DNA damage responses (DDRs) in cycling peripheral blood lymphocytes (PBL) and hematopoietic stem and progenitor cells (HSPC) from female and male donors of different age, focusing on replication stress. Transcriptomics revealed striking...

The relationship between in vitro senescence cell induction and intracellular biomolecular dysregulation is still poorly understood. In this study, we have found that a range of metabolic subphenotypes exists and is dependent on the induction method that is used. To develop understanding of these subphenotypes, we developed and employed a novel bioanalytical pipeline integrating untargeted metabolomics, label-free proteomics, and stable isotope tracing alongside cellular deformability...

Cellular senescence, an irreversible cell cycle arrest, plays a pivotal role in development, aging, and tumor suppression. However, the fundamental pathway coordinating senescence and neoplastic transformation remains unclear. Here, we describe the tumorigenic involvement of ubiquitin protein ligase E3 component n-recognin 4 (UBR4), an E3 ubiquitin ligase of the N-degron pathway, in lung adenocarcinoma (LUAD). Public genome databases revealed high UBR4 expression in LUAD patients, associated...

The cellular networks that maintain genome stability encompass numerous pathways involved in all aspects of nucleic acid metabolism. Through bioinformatic analysis, we identified the Zinc Finger CCCH-Type Containing 4 protein (ZC3H4), a suppressor of noncoding RNA (ncRNA) production, as a pivotal player in this system. Experimentally, ZC3H4 deficiency led to increased DNA damage, abnormal mitosis, and cellular senescence. Biochemical analysis and super-resolution microscopy revealed that the...

Approximately 35% of US adults over 65 are obese, highlighting the need for therapies targeting age-related metabolic issues. Fibroblast growth factor 21 (FGF21), a hormone mainly produced by the liver, improves metabolism and extends lifespan. To explore its effects without developmental confounders, we generated mice with adipocyte-specific FGF21 overexpression beginning in adulthood. When fed a high-fat diet, these mice lived up to 3.3 years, resisted weight gain, improved insulin...

Ovarian failure is a key event in female reproductive aging, resulting in the depletion of follicular reserve and a decline in fertility. In addition, it triggers systemic pathological changes, including osteoporosis and cardiovascular disease, due to decreased estrogen levels. Despite extensive study, mapping senescent ovarian cells is challenging due to the multicellular composition and heterogeneity of the ovary. In the past decade, single-cell resolution technologies have provided new...

Accumulating evidence indicates that biological aging can be accelerated by environmental exposures, collectively called the 'exposome'. The skin, as the largest and most exposed organ, can be viewed as a 'window' for the deep exploration of the exposome and its effects on systemic aging. The complex interplay across hallmarks of aging in the skin and systemic biological aging suggests that physiological processes associated with skin aging influence, and are influenced by, systemic hallmarks of...

Hyponatraemia is the most common electrolyte disorder in both inpatient and outpatient settings and mostly affects older adults, in whom intrinsic factors (such as chronic heart, liver or kidney diseases and malignancies) and extrinsic factors (such as polypharmacy and malnutrition) favouring hyponatraemia are highly prevalent. Importantly, its occurrence is expected to increase exponentially with global warming. Chronic hyponatraemia is associated with an increased risk of falling, osteoporosis...

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Older adults with established cardiovascular diseases (CVD) are at elevated risk of heart failure (HF). Frailty, a hallmark of multi-system aging, may contribute to HF development through inflammation. However, population-based evidence remains scarce. Leveraging data from 49,530 CVD patients in the UK Biobank, frailty was measured by five components: weight loss, exhaustion, low physical activity, slow walking speed, and low grip strength. We employed Cox regression models to assess the...

CONCLUSIONS: The intake of dietary live microbes is nonlinearly associated with accelerated biological age. IR partially mediated the relationship.

The second Biomarkers of Aging Symposium, jointly hosted by the National Institute on Aging (NIA) Intramural Research Program and the Biomarkers of Aging Consortium (BAC) on September 12, 2024, in Baltimore, MD, convened leading researchers, clinicians, and stakeholders in the aging field to share new developments and discuss roadmaps to advance biomarkers of aging. This meeting report summarizes the highlights of this symposium and underscores the urgent need to understand longitudinal,...

Adult hippocampal neurogenesis-the generation of new neurons in the adult brain-declines with age, contributing to cognitive deficits in aging. While the majority of mammalian studies on neurogenesis have utilized inbred mouse strains, these models do not fully capture the genetic diversity of humans, limiting the translational relevance of their findings. The Diversity Outbred (DO) mouse model, a genetically heterogeneous population, provides a promising alternative to traditional inbred...

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