Aging & Longevity

Cellular senescence contributes to age-related neurodegeneration, yet its manifestation varies across brain cell types and senescence-inducing stressors. Here, we investigated senescence hallmarks in five human brain cell lines - astrocytes, endothelial cells, microglia, oligodendrocytes, and dopaminergic-like neurons - using chronic 5-Bromodeoxyuridine treatment and validated our findings in primary cells and alternative toxin-induced models. Principal component analysis and transcriptional...

Insulin/insulin-like growth factor signaling inhibits FOXO transcription factors to control development, homeostasis, and aging. Here, we use proximity labeling to identify proteins interacting with the C. elegans FOXO DAF-16. We show that in well-fed, unstressed animals harboring active insulin signaling, DAF-16 forms a complex with the PAR-1/MARK serine/threonine kinase, a key regulator of cell polarity. PAR-1 inhibits DAF-16 accumulation and promotes DAF-16 phosphorylation at S249, at a...

Aberrant innate immune responses contribute significantly to cellular senescence, yet the precise interplay between innate immunity and senescence remains poorly characterized. Here, we elucidate the pivotal role of nuclear respiratory factor 1 (NRF1) in orchestrating innate immune responses that drive senescence and the senescence-associated secretory phenotype (SASP). NRF1 deficiency delayed cellular senescence and ameliorated age-related deterioration in multiple organs. Mechanistically, NRF1...

Organ-specific plasma protein signatures identified via proteomics profiling could be used to quantitatively track organ aging. However, the genetic determinants and molecular mechanisms underlying the organ-specific aging process remain poorly characterized. Here we integrated large-scale plasma proteomic and genomic data from 51,936 UK Biobank participants to uncover the genetic architectures underlying aging across 13 organs. We identified 119 genetic loci associated with organ aging,...

Caloric restriction prolongs lifespan and preserves health across species, with feeding times synchronized to day-night cycles further maximizing benefits. However, the mechanisms linking diet, diurnal rhythms, and lifespan remain unclear. In mice, the time point most strongly tied to dietary effects on lifespan coincides with the peak of glucocorticoid secretion (ZT12, lights-off). Caloric restriction raises circulating glucocorticoid hormone levels, implicating these signals as candidate...

During aging and cellular senescence, repetitive elements are frequently transcriptionally derepressed across species and cell types. Among these, the most abundant repeats by copy number in the human genome are Alu retrotransposons. Though Alu elements are often studied for their mutagenic potential, there is increasing appreciation for their contributions to other biological functions, including pro-inflammatory signaling and mitochondrial dysfunction. However, a comprehensive analysis of...

The cognitively-intact oldest-old (85 +) may be the most-resilient members of their birth cohort; due to survivorship effects (e.g., depletion of susceptibles), risk factors associated with brain aging biomarkers in younger samples may not generalize to the cognitively-intact oldest-old. We evaluated associations between established aging-related risk factors and brain-predicted age difference (brainPAD) in a cross-sectional cognitively-intact oldest-old sample. Additionally, we evaluated...

Local brain age (LBA) is a regional metric of brain aging that offers a spatially resolved alternative to global brain age, but whose genetic basis is unexplored. This study reports the first genome-wide association study of cortical LBA, as estimated by a deep neural network from the T(1)-weighted magnetic resonance images of 41,708 cognitively normal adults in the UK Biobank. We identified 1,212 single-nucleotide polymorphisms (SNPs) significantly associated with LBA in at least one brain...

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Transcription is regulated in part through histone proteins. Histones can be replaced with variant forms that are particularly critical in the brain and accumulate throughout the lifespan. Recent findings demonstrated that the histone variant H2BE regulates chromatin structure, neuronal transcription, and mouse behavior. However, the role of H2BE in other cell types and throughout the lifespan remains unknown. Here, we discovered that H2BE is enriched in astrocytes and accumulates with age in...

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Calcium carbonate precipitation in ageing ocean crust sequesters carbon dioxide dissolved in seawater through seafloor weathering reactions, influencing atmospheric CO(2) concentrations on million-year timescales. However, this crustal carbon sink, and the extent it balances CO(2) degassing during crustal formation at mid-ocean ridges, remain poorly quantified due to limited sampling of the vast ridge flanks where CO(2) uptake continues for millions of years. Here we quantify the carbon sink...

CONCLUSIONS: A low level of muscle strength is significantly associated with an increased risk of comorbidities among middle-aged and older adults. Therefore, incorporating strength training into comorbidity prevention and control strategies is of great importance and should be considered a key intervention. Particular emphasis should be placed on lower limb strength exercises, which do not exhibit a plateau effect in reducing comorbidity risk and can thus yield more substantial health benefits.

Given the well-established structural and functional changes in the aging brain, it is widely assumed that cognitive aging is primarily driven by robust group-level differences between young and older adults. However, our individual-level EEG functional connectivity analysis challenges this notion. We investigated the impact of cognitive training on functional brain connectivity using task-switching paradigms in 39 younger (18-25 years) and 40 older (60-75 years) women. Participants were...

This study aimed to evaluate the independent and joint effects of adherence to healthy dietary patterns and slower biological aging on the incidence of diabetic microvascular complications in individuals with type 2 diabetes mellitus (T2DM), and to assess the mediating role of biological aging. In a prospective cohort of 13,294 T2DM participants without baseline DMCs, dietary quality was assessed using a validated 10-point score, while biological aging was calculated from nine biomarkers and...

Biological ageing is a systemic, multifactorial process driven by progressive molecular and cellular alterations whose complexity necessitates systems-level approaches. Advances in high-throughput omics technologies now allow simultaneous quantification of millions of biomolecules from a single specimen, enabling longitudinal, integrative profiling across multiple molecular layers. This review synthesizes recent progress in applying genomics, epigenomics, metabolomics and microbiomics to ageing...

Organ shortage remains a major barrier in treating end-stage organ failure, with many patients dying while waiting or becoming medically unfit by the time an organ is offered. A substantial number of organs, particularly from older donors, remain unused due to concerns over age-related decline in quality. This review highlights emerging strategies to rejuvenate and optimize such organs by mitigating ischemia-reperfusion injury and reducing age-related immunogenicity. Advances in organ...

The human utricle is a vestibular organ essential for balance, a function that declines with age. With the aging population projected to double to 2 billion by 2050 and no pharmaceutical or biological treatments available, balance disorders represent a significant unmet medical need. The utricle is composed of sensory and non-sensory cells, which are closely related. Non-sensory cells have limited capacity to regenerate sensory cells and, therefore, are a relevant therapeutic target. In this...

Aging is accompanied by profound alterations in the immune system; yet, an accurate prediction of immunological age remains challenging. While transcriptomic approaches have yielded insights into immune aging, protein-level profiling and machine learning-based prediction tools remain underdeveloped. Here, we employ mass cytometry to analyse murine splenic CD45⁺ immune cells across various age groups, profiling the expression of 30 protein markers and monitoring age-related immune changes. By...

Iron-sulfur (Fe-S) clusters are essential metallocofactors that perform a multitude of biological functions^(1-7). Their synthesis is tightly regulated and defects in this process lead to severe diseases^(8-10), such as Friedreich's ataxia, which is caused by defective expression of frataxin (FXN)^(11). However, the underlying mechanisms that regulate this process remain unclear. Here we show that efficient Fe-S cluster assembly requires a fine-tuned balance in the ratio of FXN and ferredoxin-2...