Aging & Longevity

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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The prevalent itching condition associated with aging, historically referred to as senile pruritus, diminishes quality of life. Despite its impact, effective treatments remain elusive, largely due to an incomplete understanding of its pathological cause. In this study, we reveal a subset of dorsal root ganglion neurons enriched with Zn2+ that express the vesicular Zn2+ transporter TMEM163. These neurons form direct synapses with and modulate the activity of spinal NPY+ inhibitory interneurons....

Aberrant angiogenesis could contribute to the development of cognitive impairment and represent a therapeutic target for preventing dementia. However, most studies addressing angiogenesis and cognitive impairment focus on model organisms. To test the relevance of angiogenesis to human cognitive aging, we evaluated associations of circulating blood markers of angiogenesis with brain aging trajectories in a pooled two-center sample from deeply phenotyped longitudinal human cohorts (n = 435; female...

Complex lipids, essential components in biological processes, exhibit conserved age-related changes that alter membrane properties and cellular functions and are implicated as biomarkers and contributors to longevity and age-related diseases. While physical activity alleviates age-related comorbidities and physical impairments, comprehensive exploration of the underlying biological mechanisms, particularly at the level of complex lipids, remains limited. However, clinical studies suggest that...

The lifestyle patterns of top athletes are highly disciplined, featuring strict exercise regimens, nutrition plans, and mental preparation, often beginning at a young age. Recently, it was shown that physically active individuals exhibit slowed epigenetic aging and better age-related outcomes. Here, we investigate whether the extreme intensity of physical activity of Olympic champions still has a beneficial effect on epigenetic aging. To test this hypothesis, we examined the epigenetic aging of...

OBJECTIVES: Nearly half of older adults experience somnolence, but the link between medications with somnolence as an adverse effect and somnolence is unclear. This study investigated the association between polypharmacy and somnolence symptoms (excessive sleepiness or long sleep duration).

Cerebral pericytes are mural cells covering brain microvessels, organized as ensheathing, mesh and thin-strand pericytes. These latter two, together called capillary pericytes, have low levels of alpha smooth muscle actin (α-SMA), regulating basal vascular tone and applying a slow influence on cerebral blood flow. Pericytes are subject to alterations in ageing which may be even more pronounced in age-related pathologies, including microinfarcts, which usually affect a large number of vessels in...

Aging has profound effects on the body, most notably an increase in the prevalence of several diseases. An important aging hallmark is the presence of senescent cells that no longer multiply nor die off properly. Another characteristic is an altered immune system that fails to properly self-surveil. In this multi-player aging process, cellular senescence induces a change in the secretory phenotype, known as senescence-associated secretory phenotype (SASP), of many cells with the intention of...