Aging & Longevity

WNT signaling is an essential pathway regulating tissue morphogenesis and regeneration. However, harnessing the pathway for regenerative medicine has been challenging due to the lack of approaches to identify and deliver specific WNT ligands to the target tissue. Herein, we reported that WNT and R-spondin (RSPO) proteins could be transported on engineered exosomes and activate the pathway synergistically. We showed that WNT3A and RSPO1 co-treatment could effectively regulate hepatic cell fate...

Cellular senescence, a hallmark of aging, can be quantified by the gene expression composite scores for the canonical senescence pathway (CSP), senescence initiating pathway (SIP), senescence response pathway (SRP), a summary of the three, and the SenMayo gene list; however, these have not been probed in representative populations. Using RNA sequencing data from the U.S. representative Health and Retirement Study (HRS) sample (N = 3580), we examine how these composite scores relate to...

Epigenetic clocks are emerging as promising tools for examining social and health disparities. These measures are typically developed using blood DNA methylation (DNAm) data. Cheek swabs, being less invasive than blood collection, can be used to assay buccal DNAm. This study examines how buccal-originated epigenetic clocks relate to socioeconomic status (SES) and health, and compares these associations to those of blood-originated clocks applied to buccal DNAm in the German SOEP cohort (N =...

Sarcopenia is a major contributor to frailty and functional decline among older adults. Combining exercise with nutritional strategies such as creatine monohydrate (CRE) and β-hydroxy-β-methylbutyrate (HMB) supplementation may help to preserve strength and independence. To evaluate the effects of 6-week CRE + HMB supplementation combined with an integral physical conditioning (IPC) program on functional strength and body composition in physically active older adults. In a randomized,...

CONCLUSIONS: Among older adults, the risk of all-cause mortality significantly increased with a more rapid progression of tooth loss, regardless of baseline tooth count. These findings emphasize the critical importance of monitoring tooth loss progression.

Extracellular vesicles present a promising alternative to stem cells in regenerative medicine and gerontology. They offer significant advantages over cell transplantation, demonstrating potential for slowing aging and treating age-related diseases. Extracellular vesicles secreted by diverse cell types modulate inflammation, stimulate tissue regeneration, and exhibit anti-inflammatory and immunomodulatory properties. This work explores the therapeutic potential of extracellular vesicles as...

Pathogens are major drivers of cancer globally and the processes of infection and carcinogenesis unfold over decades making them difficult to observe in human or natural populations. We investigate these hidden dynamics for the foodborne trematode Opisthorchis viverrini, which is a primary cause of biliary cancer (cholangiocarcinoma) and infects 12 million people in Southeast Asia. In tumors from patients exposed to O. viverrini, we find that the earliest chromosomal amplifications carrying...

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The biological aging acceleration predicts both morbidity and mortality, while few investigations have examined its utility in evaluating transitions, e.g. development patterns, of atrial fibrillation (AF) and dementia. We aimed to investigate the utility of biological aging acceleration in predicting transitions of AF and dementia. A total of 402,955 participants (mean [SD] age: 56.5 [8.1] years; men: 45.9%) in the UK Biobank were included. Biological age was calculated using the phenotypic...

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Measuring biological aging-the underlying rate of physiological decline-has become increasingly important in predicting disease risk, guiding personalized health strategies, and advancing age-targeted therapeutics. Unlike chronological age, biological age provides a more accurate reflection of an individual's functional health and longevity potential. DNA methylation-based epigenetic clocks are established tools for estimating biological age, but existing assays often require hundreds to...

CONCLUSION: This study highlights the need to monitor body changes in older adults and develop targeted health strategies to support successful aging.

Lymphangioleiomyomatosis (LAM) is a rare disease of women in which TSC2 deficient 'LAM cells' with dysregulated mTOR signalling and recruited fibroblasts form nodules causing lung cysts and respiratory failure. We examine if mTOR dysregulation can induce senescence and impair the response to lung injury in LAM. The senescence markers p21, p16 and the SenMayo gene set are increased in LAM lungs and colocalise with alveolar type 2 cells. LAM models induce mTOR dependent senescence in alveolar type...

This study investigated how the timing and duration of 30% caloric restriction (CR) affect ovarian aging in mice. Mice were assigned to one of four groups: ad libitum (AL) control, long-term CR (3-11 months; CR/CR), early short-term CR (3-7 months; CR/AL), and late short-term CR (7-11 months; AL/CR). Long-term CR reduced body mass, improved insulin sensitivity, preserved the ovarian primordial follicle reserve, and attenuated ovarian macrophage infiltration compared to AL-fed mice. Metabolic...

We propose a new theory for aging based on dynamical systems and provide a data-driven computational method to quantify the changes at the cellular level. We use ergodic theory to decompose the dynamics of changes during aging and show that aging is fundamentally a dissipative process within biological systems, akin to dynamical systems where dissipation occurs due to non-conservative forces. To quantify the dissipation dynamics, we employ a transformer-based machine learning algorithm to...

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CONCLUSION: This review outlines multiple RMSs used for elderly individuals at risk for complications. Although the effectiveness of RMSs may depend on the content and level of responsiveness, our review underscores the necessity for further empirical research into telemonitoring interventions to fully understand their impact on elderly health outcomes and healthcare systems resources.

The mouse is a tractable model for human ovarian biology, however its utility is limited by incomplete understanding of how transcription and signaling differ interspecifically and with age. We compared ovaries between species using three-dimensional imaging, single-cell transcriptomics, and functional studies. In mice, we mapped declining follicle numbers and oocyte competence during aging; in human ovaries, we identified cortical follicle pockets and decreases in density. Oocytes had...

Efficient DNA repair might make possible the longevity of naked mole-rats. However, whether they have distinctive mechanisms to optimize functions of DNA repair suppressors is unclear. We find that naked mole-rat cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) lacks the suppressive function of human or mouse homologs in homologous recombination repair through the alteration of four amino acids during evolution. The changes enable cGAS to retain chromatin longer upon DNA...

A DNA repair function in a cytosolic sensor demonstrates a potential role in naked mole-rat longevity.