Aging & Longevity

The telomerase RNA component (Terc) constitutes a non-coding RNA critical for telomerase function, commonly associated with aging and pivotal in immunomodulation during inflammation. Our study unveils heightened susceptibility to pneumonia caused by Staphylococcus aureus (S. aureus) in Terc knockout (Terc^(ko/ko)) mice compared to both young and old infected counterparts. The exacerbated infection in Terc^(ko/ko) mice correlates with heightened inflammation, manifested by elevated interleukin-1β...

Age-related macular degeneration (AMD) is a major cause of vision loss in older adults. AMD is caused by degeneration in the macula of the retina. The retina is the highest oxygen consuming tissue in our body and is prone to oxidative damage. DNA damage is one hallmark of aging implicated in loss of organ function. Genome instability has been associated with several disorders that result in premature vision loss. We hypothesized that endogenous DNA damage plays a causal role in age-related...

This study investigates why individuals with multimorbidity-two or more chronic conditions-are more prone to adverse outcomes after surgery. In our cohort, ninety-eight of 144 participants had multimorbidity. The myocardial transcriptome and metabolites involved in energy production were measured in 53 and 57 sequential participants, respectively. Untargeted analysis of the metabolome in blood and myocardium was performed in 30 sequential participants. Mitochondrial respiration in circulating...

Age-related alterations of the immune system compromise the host's ability to respond to pathogens, but how immune aging is regulated is still poorly understood. Here, we identify via transcriptomic analysis of splenic DCs and bone marrow derived dendritic cells (BMDC) of young and aged mice, the small GTPase Rab8a as a regulator of dendritic cell (DC) functions in mice. CD11c^(+)CD11b^(+) DCs of aged in comparison to young host exhibit a diminished type I IFN response upon viral stimulation and...

This Review focuses on currently available literature describing sex differences in skeletal muscle metabolism in humans, as well as highlighting current research gaps within the field. These discussions serve as a call for action to address the current lack of sufficient sex-balanced studies in skeletal muscle research, and the resulting limitations in understanding sex-specific physiological and pathophysiological responses. Although the participation of women in studies has increased, parity...

With a growing elderly population in the European Union, age-related diseases associated with unhealthy aging pose increasing public health challenges, including a loss of independence and heightened societal burdens. The Semmelweis Study, a prospective occupational cohort study in Hungary, seeks to identify determinants of unhealthy aging, focusing on the complex relationship between lifestyle, environmental, occupational factors, and the development of chronic age-associated diseases,...

Aquaporin-1 (AQP1) is a highly conserved water-channel protein, found to be expressed by astrocytes in adult humans and non-human primates (NHPs). Upregulation of cortical AQP1 expression occurs with cancer, injury, and neurodegenerative disease, but minimal information is available about the effects of normative aging on AQP1 expression. This study leverages tissues from the oldest-old rhesus macaques, some greater than 40 years of age, from the National Institute on Aging longitudinal study of...

Restricting the intake of protein or the branched-chain amino acid isoleucine promotes healthspan and extends lifespan in young or adult mice. However, their effects when initiated in aged animals are unknown. Here we investigate the consequences of consuming a diet with 67% reduction of all amino acids (low AA) or of isoleucine alone (low Ile), in male and female C57BL/6J.Nia mice starting at 20 months of age. Both dietary regimens effectively promote overall metabolic health without reducing...

Transposable elements (TEs) are DNA sequences that expand selfishly in the genome, possibly causing severe cellular damage. While normally silenced, TEs have been shown to activate during aging. DNA 5-methylcytosine (5mC) is one of the main epigenetic modifications by which TEs are silenced and has been used to train highly accurate age predictors. Yet, one common criticism of such predictors is that they lack interpretability. In this study, we investigate the changes in TE 5mC methylation that...

Brain-wide association studies (BWAS) are a fundamental tool in discovering brain-behaviour associations^(1,2). Several recent studies have shown that thousands of study participants are required for good replicability of BWAS^(1-3). Here we performed analyses and meta-analyses of a robust effect size index using 63 longitudinal and cross-sectional MRI studies from the Lifespan Brain Chart Consortium⁴ (77,695 total scans) to demonstrate that optimizing study design is critical for increasing...

CONCLUSION: Our study underscored the impact of modifiable and non-modifiable sociodemographic determinants of mobility trajectory. There is a need for nuanced ageing policies that support mobility in older adults, considering sociodemographic inequalities through equitable resource distribution, including people of lower socioeconomic backgrounds.

Epigenetic clocks provide powerful tools for estimating health and lifespan but their ability to predict brain degeneration and neuronal damage during the aging process is unknown. In this study, we use GrimAge, an epigenetic clock correlated to several blood plasma proteins, to longitudinally investigate brain cellular microstructure in axonal white matter from a cohort of healthy aging individuals. A specific focus was made on white matter hyperintensities, a visible neurological manifestation...

Introduction The pathogenesis of aging nephropathy is yet to be elucidated. Intrarenal Angiotensin-II (AngII) and activation of the NF-κB and NLRP3 inflammasome pathways exert a relevant pathogenic role in the progression of chronic kidney disease (CKD). We sought to investigate whether monotherapy with Losartan and combined treatment with Losartan and the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) would attenuate experimental aging nephropathy. Materials and Methods Forty adult Male...

White matter hyperintensities (WMH) increase with age, with marked interindividual variation. There is a need for normative data by age and sex, to improve individualized WMH burden assessment. In this study, we pooled cross-sectional data from 15 population-based cohorts (14,876 nondemented individuals, age 18-97 years), through the Meta VCI Map consortium. Whole brain and tract-specific MRI-assessed WMH volumes were calculated in MNI-152 space. We used quantile regression to create centile...

CONCLUSIONS: Most main outcome measures in physical performance worsened over time across age groups while poor performance pattern was different between older males (strength) and females (functional mobility). We highlighted the importance of assessing strength, functional mobility, and postural control in older adults. Based on observed poor performance patterns across age groups by sex, sex-specific interventions should be implemented.

Mitochondrial calcium (mtCa^(2+)) uptake via the mitochondrial calcium uniporter (MCU) couples calcium homeostasis and energy metabolism. mtCa^(2+) uptake via MCU is rate-limiting for mitochondrial activation during muscle contraction, but its pathophysiological role and therapeutic application remain largely uncharacterized. By profiling human muscle biopsies, patient-derived myotubes, and preclinical models, we discovered a conserved downregulation of mitochondrial calcium uniporter regulator...

CONCLUSION: Machine learning algorithms, especially ensemble models, can effectively identify older adults at risk for ADL disorders. Increased outdoor activity, social engagement, and dietary adjustments are associated with a decreased risk of ADL deterioration. TRANSLATIONAL SIGNIFICANCE.

CONCLUSIONS: While the global burden of SCI is decreasing, the complex distribution across demographics and regions necessitates targeted prevention and treatment strategies to further reduce the burden and improve patient outcomes.

While it is well understood that mitochondrial DNA (mtDNA) deletion mutations cause incurable diseases and contribute to aging, little is known about the transcriptional products that arise from these DNA structural variants. We hypothesized that mitochondrial genomes containing deletion mutations express chimeric mitochondrial RNAs. To test this, we analyzed human and rat RNA sequencing data to identify, quantitate, and characterize chimeric mitochondrial RNAs. We observed increased chimeric...

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