Aging & Longevity

CONCLUSIONS: These results underscore the importance of addressing sarcopenia and related risk factors, including malnutrition, in the management and prevention of severe falls in the elderly population. Body composition analyzed in CT-scans could add value in this risk assessment. This analysis could be conducted opportunistically during CT scans performed for other purposes.

CONCLUSIONS: The global status of nutritional deficiency among older adults has improved since 1990, but the increasing prevalence of protein-energy malnutrition requires attention. Additionally, cross-country health inequalities persist, necessitating more efficient public health measures.

Human proteome data across populations have been analyzed extensively to reveal protein quantitative associations with physiological or pathological states, while the single amino acid polymorphism (SAP) has been rarely investigated. In this work, we introduce a pan-SAP workflow that relies on pan-database searching independent of individual genome sequencing. Using ten cohorts comprising 2,004 individuals related to cognition disorder and aging, we quantify the SAP sites in key proteins, such...

Aging brings with it many health issues that can make life challenging. As much of the attention is given to non-communicable diseases, there are others which are slowly becoming a matter of great concern. One such issue is cognitive frailty, which is a high risk factor for dementia, falls, fractures and hospitalization. Though not yet declared a public health concern, it deserves early detection and prevention strategies. As it is reversible if treated on time, there is a need to look into its...

CONCLUSION AND IMPLICATIONS: CogStep1 demonstrated good sensitivity and PPV to identify objective cognitive impairment among older people referred to a memory clinic. Achieving excellent sensitivity and specificity values is challenging for a very short test. However, CogStep1 proved useful for risk-stratifying patients who can benefit from further cognitive assessment, biomarker measurements, and therapeutic management, especially in the context of new anti-amyloid therapies.

Senescence and loss of cochlear hair cells is an important pathologic basis of age-related hearing loss. Lipid droplet accumulation has previously been shown to play an important role in neurodegeneration; however, its role in age-related hearing loss has not yet been investigated. LXRβ/ABCA1 is a key pathway that regulates lipid metabolism, while its dysfunction can cause abnormal accumulation of lipid droplets in neurons, leading to neurodegeneration. In this study, we found that decreased...

Executive functions (EFs), encompassing inhibition, shifting, and updating as three fundamental subdomains, are typically characterized by a unity/diversity construct. However, given the dedifferentiation trend observed in aging, it remains controversial whether the construct of EFs in older adults becomes unidimensional or maintains unity/diversity. This study aims to explore and validate the construct of EFs in older adults. At the behavioral level, we conducted confirmatory factor analysis on...

Hypoxia and interleukin (IL)-1β are independent mediators of tubulointerstitial fibrosis, the histological hallmark of chronic kidney disease (CKD). Here, we examine how hypoxia and IL-1β act in synergy to augment maladaptive proximal tubular epithelial cell (PTEC) repair in human CKD. Ex vivo patient-derived PTECs were cultured under normoxic (21% O(2)) or hypoxic (1% O(2)) conditions in the absence or presence of IL-1β and examined for maladaptive repair signatures. Hypoxic PTECs incubated...

Glioblastoma multiforme (GBM) remains a therapeutic challenge due to its aggressive nature and recurrence. This study establishes a radioresistant GBM cell model through repeated irradiation and observes a cellular senescence-like phenotype in these cells. Comprehensive genomic and transcriptomic analyses identify IFI16 as a central regulator of this phenotype and contributes to radioresistance. IFI16 activates HMOX1 transcription thereby attenuating ferroptosis by reducing lipid peroxidation,...

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Various anti-aging interventions show promise in extending lifespan, but many are ineffective or even harmful to healthspan. Ginkgolide B (GB), derived from Ginkgo biloba, reduces aging-related morbidities such as osteoporosis, yet its effects on healthspan and longevity have not been fully understood. In this study, we found that continuous oral administration of GB to female mice beginning at 20 months of age extended median survival and median lifespan by 30% and 8.5%, respectively. GB...

Accumulation of senescent cells (SnCs) plays a causative role in many age-related diseases and has also been implicated in the pathogenesis and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Senolytics that can selectively kill SnCs have the potential to be developed as therapeutics for these diseases. Here we report the finding that 753b, a dual BCL-xL/BCL-2 proteolysis-targeting chimera (PROTAC), acts as a potent and liver-tropic senolytic. We found that...

The peripheral immune system communicates with the brain through complex anatomical routes involving the skull, the brain borders, circumventricular organs and peripheral nerves. These immune-brain communication pathways were classically considered to be dormant under physiological conditions and active only in cases of infection or damage. Yet, peripheral immune cells and signals are key in brain development, function and maintenance. In this Perspective, we propose an alternative framework for...

Dietary metal ions significantly influence the lifespan and reproduction of Drosophila females. In this study, we show that not adding any of the metal ions to the diet adversely affects reproduction and lifespan. By contrast, food with no added Zn negatively impacts reproduction but does not adversely affect maternal lifespan, indicating it can dictate resource reallocation between key fitness traits. Specifically, it indicates that female flies stop producing eggs to conserve their body Zn for...

Sex differences in life span are widespread across animal taxa, but their causes remain unresolved. Alterations to the epigenome are hypothesized to contribute to vertebrate aging, and DNA methylation-based aging clocks allow for quantitative estimation of biological aging trajectories. Here, we investigate the influence of age, sex, and their interaction on genome-wide DNA methylation patterns in the brown anole (Anolis sagrei), a lizard with pronounced female-biased survival and longevity. We...

Neurotransmitters (NTs) mediate trans-synaptic signaling, and disturbances in their levels are linked to aging and brain disorders. Here, we ascribe an additional function for NTs in mediating intracellular protein aggregation by interaction with cytosolic protein fibrils. Cell-based seeding experiments revealed monoaminergic NTs as inhibitors of tau. Seeding is a disease-relevant mechanism involving catalysis by fibrils, leading to the aggregation of proteins in Alzheimer's disease and other...

Renal proximal tubular epithelial cell (PTEC) senescence and defective autophagy contribute to kidney aging, but the mechanisms remain unclear. Caveolin-1 (CAV1), a crucial component of cell membrane caveolae, regulates autophagy and is associated with cellular senescence. However, its specific role in kidney aging is poorly understood. In this study, we generated Cav1 gene knockout mice and induced kidney aging using D-galactose (D-gal). The results showed that CAV1 expression increased in the...

CONCLUSION: This study reveals significant associations between sarcopenia and various sociodemographic factors, comorbidities, and geriatric syndromes in older adults in India, suggesting potential areas for targeted intervention. However, further longitudinal studies are needed to validate these findings and clarify the causal relationships of the observed associations.

Accessible and non-invasive biomarkers that measure human ageing processes and the risk of developing age-related disease are paramount in preventative healthcare. Here, we describe a novel framework to train saliva-based DNA methylation (DNAm) biomarkers that are reproducible and biologically interpretable. By leveraging a reliability dataset with replicates across tissues, we demonstrate that it is possible to transfer knowledge from blood DNAm to saliva DNAm data using DNAm proxies of blood...

Dietary restriction (DR) is widely considered to be one of the most potent approaches to extend healthy lifespan across various species, yet it has become increasingly apparent that DR-mediated longevity is influenced by biological and non-biological factors. We propose that current priorities in the field should include understanding the relative contributions of these factors to elucidate the mechanisms underlying the beneficial effects of DR. Our work conducted in two laboratories represents...