Aging & Longevity

Ageing is characterized by progressive functional decline and increase in disease risk and imposes substantial burdens on human health. Identifying aging biomarkers in primates is crucial for advancing our understanding of human ageing and for informing interventions to mitigate age-related pathologies. However, a comprehensive grasp of these biomarkers is still lacking, hindering the translation of fundamental research into clinical practice. In this Review, we present the current knowledge on...

INTRODUCTION: Cognitive decline is part of the normal aging process, but also a major risk factor for dementia. Cognitive training interventions aim to attenuate cognitive decline, but training gains need to be transferable to untrained cognitive abilities to influence everyday function. Furthermore, the neurobiological basis of cognitive training gain transfer remains elusive. A possible candidate is increased bilateral hemisphere usage enabled by efficient structural connectivity, especially...

INTRODUCTION: Previous studies provided inconclusive results regarding the effects of aging on the ability to flexibly switch between task rules (local switch cost). The goal of the present study was to investigate the influence of age on the local switch costs at two levels of difficulty (easy task switching: two task rules vs. difficult task switching: four task rules).

CONCLUSION: Hand dexterity (NHPT) and specific functional mobility tasks (5CRT, 4MWT) are robust, independent predictors of cognition in older adults. Grip strength, balance, usual gait speed, and gait variability offer limited additional value when assessed together. The NHPT and timed SPPB components are accessible, pragmatic tools for motor-cognitive research and screening.

Autophagosome closure by the endosomal sorting complex required for transport (ESCRT) complex is a prerequisite for their dynamin 2 (DNM2)-dependent release from the recycling endosome and subsequent lysosomal clearance. However, the mechanism that coordinates autophagosome closure and release is unknown. We identified that the Alzheimer's disease-associated protein bridging integrator 1 (BIN1) is a critical mediator of this coordination. Prior to autophagosome closure, BIN1 is held at...

Oxytocin is essential in shaping social behavior across the lifespan. Although the role of oxytocin signaling in parental care has been widely investigated, little is known about its function in social behavior during early life. We studied the role of oxytocin in mouse pup social behavior during acute separation from the mother as well as upon reunion. The activity of oxytocin neurons was increased by acute maternal separation. Behaviorally, maternally separated pups emitted more ultrasonic...

Neural oscillations comprise periodic and aperiodic components, which have been linked to cognitive functions. Changes in oscillatory activity as a function of age and musical training may related to cognitive decline and the protective effects of lifelong musical training. However, there are inconsistencies in prior studies assessing the changes in alpha oscillations with age and musical training experience, which did not consider the putative impact of the aperiodic activity. In this study, we...

Influenza A virus (IAV) infection causes significantly greater morbidity and mortality in the elderly population, but the molecular mechanisms in the aging process responsible for severe infection remain unclear. In this study, we found that increased severity in IAV infection and reduced innate immune response correlated with extensive mitophagy in senescent human cells and in the lung of aged mice. Apolipoprotein D (ApoD) was identified as strongly elevated in the lungs and sera of aged human...

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...

No abstract

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...

No abstract

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....