Aging & Longevity

The endoplasmic reticulum (ER) stress-response is an adaptive cellular mechanism activated by an accumulation of unfolded proteins within the ER. Although recent evidence shows that the ER stress-response is activated in aged tissues, and therefore ER stress is considered a candidate driver of aging, the spatiotemporal regulation and roles of the ER stress-response during aging remain unclear. To address this research gap, we introduced an Ire1-Xbp1s ER stress-response pathway-sensitive reporter...

Aging is a risk factor for atrial fibrillation (AF). In 19-month-old mice, increases in AF inducibility are associated with enhanced protein levels of fat mass and obesity-associated protein (Fto), and reduced N6-methyladenosine (m6A) modification in atrial tissue. Whether Fto-regulated m6A demethylation is involved in aging-induced AF remains unclear. AF inducibility and electrophysiology were performed through programmed stimulation and optical mapping. The intensities of slow delayed...

Valvular heart disease (VHD) is a highly prevalent age-associated cardiovascular pathology. VHD can be characterised by stenosis, an increase in valve stiffening commonly due to leaflet calcification, or regurgitation, where backflow of blood can occur as a result of valve remodelling. At present, there is a paucity of spontaneous animal models of valve disease which would aid mechanistic investigations and allow therapeutic screening. Here, we report a spontaneously occurring zebrafish valve...

A decrease in osteoblast number and bone formation are seminal contributors to age-related osteoporosis. However, the aging-associated molecular mechanisms that impact osteoblast precursors, osteoblasts, osteocytes, and other bone mesenchymal cell types remain unclear. We performed single-cell RNA-sequencing of mesenchymal cells present at the endosteum and periosteum of young and old C57BL/6 mice of both sexes. Osteoblast precursors and osteoblasts from female endosteum exhibited the greatest...

Many studies have compared gene expression in young and old samples to gain insights on aging, the primary risk factor for most chronic diseases. However, these studies only identify associations without distinguishing drivers of aging from compensatory geroprotective responses or incidental downstream effects. Here, we introduce a workflow to characterize causal effects of differentially expressed genes on lifespan. First, we performed a meta-analysis of 25 gene expression datasets comprising...

Autophagy is intricately linked with protective cellular processes, including mitochondrial function, proteostasis, and cellular senescence. Animal studies have indicated that autophagy becomes dysfunctional with aging and may contribute to T cell immunosenescence. In humans, it remains unclear whether autophagy is impaired in CD4^(+) T cells as people age. To answer this question, we examined basal and inducible autophagic activity in a series of experiments comparing CD4^(+) T cells from...

Immune cell metabolism is increasingly recognized as an important regulator of immune function, but its role in age-related immune dysfunction, chronic inflammation, and cardiometabolic complications in humans remains incompletely understood. This study investigated the impact of aging on monocyte metabolic and functional signatures in a healthy elderly population. We aimed to leverage these immunometabolic signatures to identify healthy elderly individuals with reduced immune cell fitness and,...

Circular RNAs (circRNAs) are emerging as crucial regulators of biological processes and have been implicated in age-related diseases. Few studies have explored age-related circRNA expression in the human brain across the adult lifespan. This study aims to identify age-related differentially expressed circRNAs in human post-mortem dorsolateral prefrontal cortex (DLPFC) samples, a region critically involved in cognition that exhibits early signs of age-related changes. Total RNA sequencing was...

CONCLUSIONS AND IMPLICATIONS: In China, technophobia among older adults is moderate, particularly concerning privacy concerns dimensions. Higher technophobia levels are observed in those who are older, have lower education and income, and live in rural areas. This trend is global amid aging and digitalization. Health care professionals and policymakers should identify high-risk groups and risk factors, developing targeted interventions through multidisciplinary collaboration to reduce...

Non-invasive brain stimulation applied to the prefrontal cortex (PFC) has been shown to improve cognitive outcomes in older adults with cognitive impairments (Miller et al., 2023). However, the differential impact of left versus right dorsolateral prefrontal cortex (DLPFC) stimulation on prefrontal oxygenation levels, as well as its modulation across age groups, remains insufficiently understood. 45 adults completed a within-subjects design completing 4 cognitive tasks before and after...

CONCLUSIONS: LA mitigated age-related cognitive deficits by modulating neuroinflammation through PPARγ/NF-κB suppression. Our findings highlighted the therapeutic potential of LA in aging-related cognitive decline and the role of the PPARγ/NF-κB axis in neuroinflammation regulation. As an exploratory study with a limited sample size, these findings offer promising insights that would benefit from future confirmation in larger cohorts.

CONCLUSION: Tryptophan supplementation, HIIT, and their combination similarly can influence muscle atrophy markers and adipose tissue inflammation in aging during HFD feeding.

Progressive multiple sclerosis (PMS) involves a persistent, maladaptive inflammatory process with numerous cellular drivers. We generated induced neural stem cells (iNSCs) from patient fibroblasts through a direct reprogramming protocol that preserved their epigenome, which revealed a PMS-specific hypomethylation of lipid metabolism and interferon (IFN) signaling genes. Single-cell multi-omics uncovered a novel, disease-associated radial glia-like cell (DARG) subpopulation in PMS cell lines...

Rapid remodeling of actin filament (F-actin) networks is essential for the movement and morphogenesis of eukaryotic cells. The conserved actin-binding proteins coronin, cofilin, and actin-interacting protein 1 (AIP1) act in synergy to promote rapid F-actin network disassembly, but the underlying mechanisms have remained elusive. Here, using cryo-electron microscopy (cryo-EM), we uncover the concerted molecular actions of coronin, cofilin, and AIP1 that lead to actin filament aging and severing....

CONCLUSIONS AND IMPLICATIONS: Our findings suggest that exercise interventions involving minimal equipment show promising benefits in various outcome domains among community-dwelling adults with dementia. However, given the low certainty of evidence, more studies of higher quality are needed to confirm these findings.

Cognitive reserve mitigates aging-related cognitive decline and frailty, yet current assessments lack neurobiological specificity. We aimed to develop a noninvasive, functional near infrared spectroscopy (fNIRS)-based machine learning model to classify cognitive reserve levels in older adults with cognitive frailty. Seventy-one community-dwelling adults underwent resting-state and task-based (Stroop, n-back) fNIRS scans. Graph theory metrics and task-related β-values were extracted. Support...

CONCLUSIONS: D/AO and ND/AO were both associated with higher risk of CVD among middle-aged and older adults, which was more pronounced in people younger than 65 years old. The presence of dynapenia further increased the risk of CVD in individuals with AO.

Global population aging is increasing the demand for Long-Term Care Facilities to support older adults with complex health needs. The Prescription Day LTCFs project is a national multicenter point-prevalence study, conducted by the Italian Society of Gerontology and Geriatrics in collaboration with the ANASTE Humanitas Foundation, investigated medication prescription patterns and administration practices in 3,400 residents across 82 facilities in Italy. Participants had a mean age of 84.7 years,...

Aging is accompanied by progressive declines in metabolic and cognitive functions. Growth hormone secretagogue receptor (GHSR), a receptor for the gut hormone ghrelin, is highly expressed in neurons and plays a crucial role in metabolic regulation. We previously reported that aged global GHSR-ablated mice are lean and insulin-sensitive, and that neuronal GHSR-deleted mice (Syn1-cre;Ghsr^(f/f)) completely prevent diet-induced obesity. However, the role of neuronal GHSR in metabolic and cognitive...

CONCLUSION: This study first identifies abnormal TmP/GFR as a novel biomarker of physical dysfunction in older adults. Additionally, its causal relationship further substantiates the reliability of this finding. Abnormal TmP/GFR enables early detection of physical dysfunction, facilitating the prevention of severe adverse outcomes.