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ABSTRACT Protein aggregation occurs as a consequence of perturbations in protein homeostasis that can be triggered by environmental and cellular stresses. The accumulation of protein aggregates has been associated with aging and other pathologies in eukaryotes, and in bacteria with changes in growth rate, stress resistance and virulence. Numerous past studies, mostly performed in Escherichia coli, have led to a detailed understanding of the functions of the bacterial protein quality control machinery in preventing and reversing protein aggregation. However, more recent research points toward unexpected diversity in how phylogenetically different bacteria utilize components of this machinery to cope with protein aggregation. Furthermore, how persistent protein aggregates localize and are passed on to progeny during cell division and how their presence impacts reproduction and the fitness of bacterial populations remains a controversial field of research. Finally, although protein aggregation is generally seen as a symptom of stress, recent work suggests that aggregation of specific proteins under certain conditions can regulate gene expression and cellular resource allocation. This review discusses recent advances in understanding the consequences of protein aggregation and how this process is dealt with in bacteria, with focus on highlighting the differences and similarities observed between phylogenetically different groups of bacteria. This review discusses recent advances in understanding the consequences of protein aggregation and how this process is dealt with in bacteria, with focus on highlighting the differences and similarities observed between phylogenetically different groups of bacteria.

Stress over the lifespan is thought to promote accelerated aging and early disease. Telomere length is amarker of cell aging that appears to be one mediator of this relationship. Telomere length is associated with early adversity and with chronic stressors in adulthood in many studies. Although cumulative lifespan adversity should have bigger impacts than single events, it is also possible that adversity in childhood has larger effects on later life health than adult stressors, as suggested by models of biological embedding in early life. No studies have examined the individual vs. cumulative effects of childhood and adulthood adversities on adult telomere length. Here, we examined the relationship between cumulative childhood and adulthood adversity, adding up a range of severe financial, traumatic, and social exposures, as well as comparing them to each other, in relation to salivary telomere length. We examined 4,598 men and women from the US Health and Retirement Study. Single adversities tended to have nonsignificant relations with telomere length. In adjusted models, lifetime cumulative adversity predicted 6% greater odds of shorter telomere length. This result was mainly due to childhood adversity. In adjusted models for cumulative childhood adversity, the occurrence of each additional childhood event predicted 11% increased odds of having short telomeres. This result appeared mainly because of social/traumatic exposures rather than financial exposures. This study suggests that the shadow of childhood adversity may reach far into later adulthood in part through cellular aging.

Microplastics and nanoplastics (MNPs) are ubiquitous environmental contaminants. Their prevalence, persistence, and increasing industrial production have led to questions about their long-term impact on human and animal health. This narrative review describes the effects of MNPs on oxidative stress, inflammation, and aging. Exposure to MNPs leads to increased production of reactive oxygen species (ROS) across multiple experimental models, including cell lines, organoids, and animal systems. ROS can cause damage to cellular macromolecules such as DNA, proteins, and lipids. Direct interaction between MNPs and immune cells or an indirect result of oxidative stress-mediated cellular damage may lead to increased production of pro-inflammatory cytokines throughout different MNP-exposure conditions. This inflammatory response is a common feature in the pathogenesis of neurodegenerative, cardiovascular, and other age-related diseases. MNPs also act as cell senescence inducers by promoting mitochondrial dysfunction, impairing autophagy, and activating DNA damage responses, exacerbating cellular aging altogether. Increased senescence of reproductive cells and transfer of MNPs/induced damages from parents to offspring in animals further corroborates the transgenerational health risks of the tiny particles. This review aims to provoke a deeper investigation into the notorious effects these pervasive particles may have on human well-being and longevity.

Climate change represents a major challenge for avian species. It is characterized by an increase in average ambient temperatures, but also by an increase of extreme weather events, such as heatwaves and cold snaps. These abrupt temperature changes can modify the immediate and long‐term survival prospects of nestling birds, when their thermoregulatory capacities are still not fully developed. While immediate nestling survival can easily be measured, long‐term survival is more challenging to evaluate. Early‐life telomere length has been suggested as a potential biomarker of future fitness prospects. To evaluate the potential impact of changes in early‐life temperature, we thus experimentally increased (ca +2.8°C) and decreased (ca −1.7°C) average nestbox temperatures in wild pied flycatchers Ficedula hypoleuca during nestling postnatal growth, and measured nestling telomere length before fledging. Shorter telomeres were observed in individuals exposed to either experimental heating or cooling during growth. Our results suggest that long‐term survival prospects, or long‐term performance of individuals exposed to abrupt changes in early‐life temperature, may be decreased.

Aging leads to a decline in physiological reserves, an increase in age‐related diseases, reduced functional ability and a shortened healthspan. While molecular markers of chronological aging exist, their link to general health and intrinsic capacity (IC), a composite measure of physical and mental capacities, remains unclear. This study integrates the WHO's Healthy Aging framework with geroscience to explore fibroblasts as indicators of health. We assessed primary skin fibroblasts from 133 individuals aged 20–96, evaluating their ability to maintain tissue structure, modulate immune responses and regulate metabolism (SIM functions). By combining functional and molecular analyses, we investigated the relationship between fibroblast performance, chronological age and IC. Our results demonstrate that fibroblast SIM functions are modified with stressors and age, correlating with IC rather than just chronological age. Notably, fibroblasts from pre‐frail and frail individuals exhibited reduced mitochondrial respiration and lower extracellular periostin levels, with periostin being able to capture IC status, irrespective of age and sex, reflecting a cellular ‘health memory’. The SIM paradigm provides a complementary framework to the established hallmarks of aging, advancing our understanding of how cellular aging impacts functional decline. These findings suggest that fibroblast‐derived markers could serve as indicators of frailty and reduced IC, enabling early detection of individuals at risk for health deterioration and laying the foundation for early identification of functional decline. Human skin fibroblasts in vitro preserve the memory of age and health.

After Saccharomyces cerevisiae cells cultured in a medium with glucose consume glucose, the sub-populations of quiescent and non-quiescent cells develop in the budding yeast culture. An age-related chronology of quiescent and non-quiescent yeast cells within this culture is discussed here. We also describe various hallmarks of quiescent and non-quiescent yeast cells. A complex aging-associated program underlies cellular quiescence in budding yeast. This quiescence program includes a cascade of consecutive cellular events orchestrated by an intricate signaling network. We examine here how caloric restriction, a low-calorie diet that extends lifespan and healthspan in yeast and other eukaryotes, influences the cellular quiescence program in S. cerevisiae. One of the main objectives of this review is to stimulate an exploration of the mechanisms that link cellular quiescence to chronological aging of budding yeast. Yeast chronological aging is defined by the length of time during which a yeast cell remains viable after its growth and division are arrested, and it becomes quiescent. We propose a hypothesis on how caloric restriction can slow chronological aging of S. cerevisiae by altering the chronology and properties of quiescent cells. Our hypothesis posits that caloric restriction delays yeast chronological aging by targeting four different processes within quiescent cells.

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disorder affecting the central nervous system. Evidence suggests that age‐related neurodegeneration contributes to disability progression during the chronic stages of MS. Aging is characterized by decreased regeneration potential and impaired myelin repair in the brain. It is hypothesized that accelerated cellular aging contributes to the functional decline associated with neurodegenerative diseases. We assessed the impact of aging on myelin content in the corpus callosum (CC) and compared aging with the long‐term demyelination (LTD) consequents induced by 12 weeks of feeding with a cuprizone (CPZ) diet. Initially, evaluating myelin content in 2‐, 6‐, and 18‐month‐old mice revealed a reduction in myelin content, particularly at 18 months. Myelin thickness was decreased and the g‐ratio increased in aged mice. Although a lower myelin content and higher g‐ratio were observed in LTD model mice, compared to the normally aged mice, both aging and LTD exhibited relatively similar myelin ultrastructure. Our findings provide evidence that LTD exhibits the hallmarks of aging such as elevated expression of senescence‐associated genes, mitochondrial dysfunction, and high level of oxidative stress as observed following normal aging. We also investigated the senescence‐associated β‐galactosidase activity in O4+ late oligodendrocyte progenitor cells (OPCs). The senescent O4+/β‐galactosidase+ cells were elevated in the CPZ diet. Our data showed that the myelin degeneration in CC occurs throughout the lifespan, and LTD induced by CPZ accelerates the aging process which may explain the impairment of myelin repair in patients with progressive MS. We examined the effects of aging on myelin content in the corpus callosum (CC) and compared it with long‐term demyelination (LTD) induced by a 12‐week cuprizone diet. We investigated myelin changes, mitochondrial disruption, senescence occurrence, gliosis, and the aging of oligodendrocytes in the CC. Our findings revealed that myelin degeneration in the CC occurs throughout the lifespan, and CPZ might accelerate the aging process, which potentially leading to disruption in myelin repair.

Human life expectancy is constantly increasing and aging has become a major risk factor for many diseases, although the underlying gene regulatory mechanisms are still unclear. Using transcriptomic and chromosomal conformation capture (Hi‐C) data from human skin fibroblasts from individuals across different age groups, we identified a tight coupling between the changes in co‐regulation and co‐localization of genes. We obtained transcription factors, cofactors, and chromatin regulators that could drive the cellular aging process by developing a time‐course prize‐collecting Steiner tree algorithm. In particular, by combining RNA‐Seq data from different age groups and protein–protein interaction data we determined the key transcription regulators and gene regulatory changes at different life stage transitions. We then mapped these transcription regulators to the 3D reorganization of chromatin in young and old skin fibroblasts. Collectively, we identified key transcription regulators whose target genes are spatially rearranged and correlate with changes in their expression, thereby providing potential targets for reverting cellular aging. We present a prize‐collecting Steiner tree algorithm to discover key transcription regulators in cellular aging from time‐course RNA‐Seq data. Integrating Hi‐C data, our analysis demonstrates spatial rearrangements among the target genes controlled by these regulators during aging. Our findings suggest a tight coupling between changes in co‐regulation and co‐localization of age‐associated genes, thereby providing potential targets for reverting cellular aging.

Alzheimer’s disease (AD) is a condition characterized by the gradual degeneration of the nervous system that poses significant challenges to cognitive function and overall mental health. Given the increasing global life expectancy, there is an urgent need for effective strategies to prevent and manage Alzheimer’s disease, with a particular focus on anti-aging interventions. Recent scientific advancements have unveiled several promising strategies for combating Alzheimer’s disease (AD), ranging from lifestyle interventions to cutting-edge pharmacological treatments and therapies targeting the underlying biological processes of aging and AD. Regular physical exercise, cognitive engagement, a balanced diet, and social interaction serve as key pillars in maintaining brain health. At the same time, therapies target key pathological mechanisms of AD, such as amyloid-beta accumulation, tau abnormalities, neuroinflammation, mitochondrial dysfunction, and synaptic loss, offering potential breakthroughs in treatment. Moreover, cutting-edge innovations such as gene therapy, stem cell transplantation, and novel drug delivery systems are emerging as potential game-changers in the fight against AD. This review critically evaluates the latest research on anti-aging interventions and their potential in preventing and treating Alzheimer’s disease (AD) by exploring the connections between aging mechanisms and AD pathogenesis. It provides a comprehensive analysis of both well-established and emerging strategies, while also identifying key gaps in current knowledge to guide future research efforts.

Recently, cellular senescence-induced unstable carotid plaques have gained increasing attention. In this study, we utilized bioinformatics and machine learning methods to investigate the correlation between cellular senescence and the pathological mechanisms of unstable carotid plaques. Our aim was to elucidate the causes of unstable carotid plaque progression and identify new therapeutic strategies. First, differential expression analysis was performed on the test set GSE43292 to identify differentially expressed genes (DEGs) between the unstable plaque group and the control group. These DEGs were intersected with cellular senescence-associated genes to obtain 40 cellular senescence-associated DEGs. Subsequently, key genes were then identified through weighted gene co-expression network analysis, random forest, Recursive Feature Elimination for Support Vector Machines algorithm and cytoHubba plugin. The intersection yielded 3 CSA-signature genes, which were validated in the external validation set GSE163154. Additionally, we assessed the relationship between these CSA-signature genes and the immune landscape of the unstable plaque group. This study suggests that cellular senescence may play an important role in the progression mechanism of unstable plaques and is closely related to the influence of the immune microenvironment. Our research lays the foundation for studying the progression mechanism of unstable carotid plaques and provides some reference for targeted therapy.