Aging & Longevity

Entropy, characterized by increased disorder throughout biological systems, can be quantified by homeostatic dysregulation (HD). One potential measure of HD is the dispersion of points from a normal value, approximated at the individual level by Mahalanobis distance (D(M)). We hypothesized that greater HD in electrocardiogram (ECG) would also reflect greater HD in the musculoskeletal system which, in turn, would be associated with age and manifest as an increased risk of fracture independently...

The tumor microenvironment (TME) imposes immunologic and metabolic stresses sufficient to deviate immune cell differentiation into dysfunctional states. Oxidative stress originating in the mitochondria can induce DNA damage, most notably telomeres. Here, we show that dysfunctional T cells in cancer did not harbor short telomeres indicative of replicative senescence but rather harbored damaged telomeres, which we hypothesized arose from oxidative stress. Chemo-optogenetic induction of highly...

Aging is the greatest risk factor for cardiovascular diseases (CVD) and is characterized by inflammation, oxidative stress, and cellular senescence. Cellular senescence is a state of persistent cell cycle arrest triggered by stressors such as DNA damage and telomere attrition. Senescent endothelial cells (ECs) can impair vascular function and promote inflammation, thereby contributing to CVD progression. Senolytics, a class of drugs that selectively eliminate senescent cells, have been shown to...

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Circadian oscillations of gene transcripts rely on a negative feedback loop executed by the activating BMAL1-CLOCK heterodimer and its negative regulators PER and CRY. Although circadian rhythms and CLOCK protein are mostly absent during embryogenesis, the lack of BMAL1 during prenatal development causes an early aging phenotype during adulthood, suggesting that BMAL1 performs an unknown non-circadian function during organism development that is fundamental for healthy adult life. Here, we show...

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Membraneless organelles assembled by liquid-liquid phase separation interact with diverse membranous organelles to regulate distinct cellular processes. It remains unknown how membraneless organelles are engaged in mitochondrial homeostasis. Here we demonstrate that mitochondria-associated translation organelles (MATOs) mediate local synthesis of proteins required for structural and functional maintenance of mitochondria. In Caenorhabditis elegans, the RNA-binding protein LARP-1 (La-related...

Aging is a major risk factor for various neurological disorders, including Alzheimer's disease, and is associated with the accumulation of senescent cells, which can themselves propagate the senescence process through paracrine signaling. Migrasomes are organelles that form during cellular migration, detach from parent cells and mediate intercellular communication. Here we demonstrate that border-associated macrophages (BAMs) acquire senescence-associated properties during early brain aging,...

In the past century, the human Lifespan has doubled. However, this is not equivalent to Healthspan which refers to the number of years spent healthy and free from disease. Women have an additional level of complexity on the path to optimal healthspan where health resilience dramatically decreases following menopause and this is due to their ovaries aging by midlife. It still remains elusive on why and how the ovaries in women, albeit their distinct and vital reproductive functions, start to age...

This study aims to investigate the predictive value of combined phenotypic age and phenotypic age acceleration (PhenoAgeAccel) for benign prostatic hyperplasia (BPH) and develop a machine learning-based risk prediction model to inform precision prevention and clinical management strategies. The study analyzed data from 784 male participants in the US National Health and Nutrition Examination Survey (NHANES, 2001-2008). Phenotypic age was derived from chronological age and nine serum biomarkers....

To evaluate a simplified version of the Clinical Frailty Scale (SCFS) among older adults presenting to the emergency department (ED) with acute dyspnea. In this retrospective single-center cohort study, we included patients from the Acute Dyspnea Study (ADYS) cohort. Severity of illness was assessed using the Medical Emergency Triage and Treatment System (METTS). SCFS was operationalized using existing data on municipal care services from the ADYS database and divided into three levels. SCFS 1:...

Triple-negative breast cancers (TNBCs) lack predictive biomarkers to guide immunotherapy, especially during early-stage disease. To address this issue, we used single-cell RNA sequencing, bulk transcriptomics, and pathology assays on samples from 171 patients with early-stage TNBC receiving chemotherapy with or without immunotherapy. Our investigation identified an enriched subset of interferon (IFN)-induced CD8^(+) T cells in early TNBC samples, which predict immunotherapy nonresponsiveness....

CONCLUSIONS: When evaluating mortality using the NHATS Sensitive files, investigators should consider censoring all participants who are lost to follow-up at the time of the last completed interview, recognizing potential trade-offs in terms of reductions in power and precision.

Aging leads to chronic inflammation that is linked to aging-associated conditions and diseases. Multiple immune pathways become activated during aging, posing a challenge to effectively reduce aging-associated inflammation. SIRT2, an NAD^(+)-dependent deacetylase, suppresses several immune pathways that become activated during aging and may represent an attractive target to broadly dampen aging-associated inflammation. Here, we show that SIRT2 deficiency leads to increased inflammation governed...

The aging population worldwide faces an increasing burden of age-related conditions, with Alzheimer's disease being a prominent neurodegenerative concern. Drug repurposing, the practice of identifying new therapeutic applications for existing drugs, offers a promising avenue for accelerated intervention. In this study, we utilized the yeast Saccharomyces cerevisiae to screen a library of 1760 FDA-approved compounds, both with and without rapamycin, to assess potential synergistic effects on...

Cognitive decline is common in multiple sclerosis (MS), although neural mechanisms are not fully understood. The objective was to investigate the impact of mild cognitive impairment (MCI) on the relationship between resting state functional connectivity (RSFC) and cognitive function in older adults with multiple sclerosis (OAMS) and age matched healthy controls. Participants underwent magnetic resonance imaging (MRI) scans and cognitive assessments. The Oral Symbol Digit Modalities Test (SDMT)...

Beyond their classical functions as redox cofactors, recent fundamental and clinical research has expanded our understanding of the diverse roles of nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) in signaling pathways, epigenetic regulation and energy homeostasis. Moreover, NAD and NADP influence numerous diseases as well as the processes of aging, and are emerging as targets for clinical intervention. Here, we summarize safety, bioavailability and...

The global surge in the population of people 60 years and older, including that in China, challenges healthcare systems with rising age-related diseases. To address this demographic change, the Aging Biomarker Consortium (ABC) has launched the X-Age Project to develop a comprehensive aging evaluation system tailored to the Chinese population. Our goal is to identify robust biomarkers and construct composite aging clocks that capture biological age, defined as an individual's physiological and...

CONCLUSIONS: The results emphasize the need for enhanced communication and personalized care to better support frail older adults in engaging in physical activity during hospitalization. Customized advice and tailored physical activities are key to supporting them in staying active and healthy. Effective strategies, teamwork, and resource allocation are needed to meet these older adults' needs and develop interventions that ensure proper care and support.

CONCLUSION: The AMCOHF study will contribute to knowledge about markers to predict an accelerated decline in intrinsic capacity in an early stage. This knowledge is important to deploy prevention strategies at an earlier stage in life then those currently undertaken, ultimately reducing healthcare costs and contributing to a healthy aging population.