Aging & Longevity
Physical activity and DNA methylation-based markers of ageing in 6208 middle-aged and older Australians: cross-sectional and longitudinal analyses
Epigenetic age quantifies biological age using DNA methylation information and is a potential pathway by which physical activity benefits general health. We aimed to assess the cross-sectional and longitudinal associations between physical activity and epigenetic age in middle-aged and older Australians. Blood DNA methylation data for 6208 participants (40% female) in the Melbourne Collaborative Cohort Study (MCCS) were available at baseline (1990-1994, mean age, 59 years) and, of those, for...
A neural implementation of cognitive reserve: Insights from a longitudinal fMRI study of set-switching in aging
Aging is often accompanied by changes in brain structure and executive functions, particularly in tasks involving cognitive flexibility, such as task-switching. However, substantial individual differences in the degree of cognitive impairment indicate that some individuals can cope with brain changes more effectively than others, suggesting higher cognitive reserve (CR). This study identified a neural basis for CR by examining the longitudinal relationship between task-related brain activation,...
Autophagy-dependent splicing control directs translation toward inflammation during senescence
The cellular proteome determines the functional state of cells and is often skewed to direct pathological conditions. Autophagy shapes cellular proteomes primarily through lysosomal degradation of either damaged or unnecessary proteins. Here, we show that autophagy directs the senescence-specific translatome to fuel inflammation by coupling selective protein degradation with alternative splicing. RNA splicing is significantly altered during senescence, some of which surprisingly depend on...
BRD7 regulates cellular senescence and apoptosis in ALS by modulating p21 expression and p53 mitochondrial translocation respectively
Cellular senescence is involved in the progression of neurodegenerative diseases. Motor neurons exhibit senescence-like alterations in ALS. BRD7, identified as a regulatory factor associated with cellular senescence, its function in ALS remains unclear. This study aims to investigate the potential role and mechanisms of BRD7 in ALS. We analyzed RNA levels using qRT-PCR, protein levels through immunofluorescence and western blot, and apoptosis via TUNEL staining. Cell transfection was conducted...
SIRT6-dependent functional switch via K494 modifications of RE-1 silencing transcription factor
RE-1 silencing transcription factor (REST) is a key repressor of neural genes. REST is upregulated under stress signals, aging and neurodegenerative diseases, but although it is upregulated, its function is lost in Alzheimer's Disease. However, why it becomes inactive remains unclear. Here, we show that the NAD-dependent deacetylase SIRT6 regulates REST expression, location and activity. In the absence of SIRT6, REST is overexpressed but mislocalized, leading to a partial loss of its activity...
Spermidine mediates acetylhypusination of RIPK1 to suppress diabetes onset and progression
It has been established that N-acetyltransferase (murine NAT1 (mNAT1) and human NAT2 (hNAT2)) mediates insulin sensitivity in type 2 diabetes. Here we show that mNAT1 deficiency leads to a decrease in cellular spermidine-a natural polyamine exhibiting health-protective and anti-ageing effects-but understanding of its mechanism is limited. We identify that mNAT1 and hNAT2 modulate a type of post-translational modification involving acetylated spermidine, which we name acetylhypusination, on...
Association of low socioeconomic status with cognitive decline among older persons in underdeveloped areas in China - a data analysis of the Gansu aging study
CONCLUSION: This study suggested that, approximately one-quarter of older persons suffered from CI in Gansu, China. Low SES was substantially associated with risk of CI. Although interventions to modify traditional risk factors may decrease the risk of CI, disparities by SES may remain without addressing SES itself.
Sequential multiple mediating effect of loneliness and family health on physical frailty and willingness to age at home in older adults: a national survey in China
CONCLUSIONS: Reducing physical frailty in older adults, reducing their sense of loneliness, and enhancing their family health is essential, as it can increase their levels of confidence with regard to ageing at home.
Older patients affected by COVID-19: investigating the existence of biological phenotypes
CONCLUSION: Biological phenotypes might be used to identify different clinical and functional phenotypes in individuals affected by COVID-19.
Exploring the barriers to the development of organizational health literacy in health institutions to meet the needs of older patients from multiple perspectives: a mixed-methods study
CONCLUSION: The two most vulnerable aspects of OHL in medical institutions regarding the needs of older patients are health information and communication. The factors influencing the construction of OHL in medical institutions are multifaceted, encompassing micro, meso, and macro levels. At the macro level, it is essential for medical institutions to enhance leadership awareness of OHL and to incorporate its development into institutional strategic plans. At the meso-level, medical institutions...
Cat brains age like ours - and could help scientists to understand cognitive decline
No abstract
Factors associated with the occupational balance in caregivers of people with dementia: A cross-sectional study from the ATENEA project
CONCLUSIONS: This study identified several associated factors with the OB of CGs of persons with dementia. Specifically, we remarked that the CGs' education, employment status, household chores assistance, overload presence, psychological distress symptoms and the functional level of the person with dementia who cared for were important variables that should be considered when evaluating OB or creating OB-related interventions in CGs.
Effects of home-based exercise alone or combined with cognitive training on cognition in community-dwelling older adults: A randomized clinical trial
CONCLUSION: Remote combined training may lead to larger improvement in executive functioning than exercise alone. Physical exercise showed a dose-related improvement in working and episodic memory performances. The combination of cognitive interventions mitigated the effects of exercise on episodic memory. These results suggest that home-based exercise and cognitive training may help improve older adults' cognition.
Characterizing the oral and gastrointestinal microbiome associated with healthy aging: insights from long-lived populations in Northeastern China
The oral and gastrointestinal (GI) tract microbiota in humans is susceptible to geographical influences and represents vital factors impacting healthy aging. The northeastern region of China, characterized by distinct dietary and climatic conditions, significantly influences the human microbiome composition. However, the microbial structure of the entire long-lived population in this area has not been evaluated. This study recruited a cohort of 142 individuals aged 55-102 residing in Northeast...
Metabolite signatures of chronological age, aging, survival, and longevity
Metabolites that mark aging are not fully known. We analyze 408 plasma metabolites in Long Life Family Study participants to characterize markers of age, aging, extreme longevity, and mortality. We identify 308 metabolites associated with age, 258 metabolites that change over time, 230 metabolites associated with extreme longevity, and 152 metabolites associated with mortality risk. We replicate many associations in independent studies. By summarizing the results into 19 signatures, we...
The <em>R1441C-Lrrk2</em> mutation induces myeloid immune cell exhaustion in an age- and sex-dependent manner in mice
Age is the greatest risk factor for many neurodegenerative diseases, yet immune system aging, a contributor to neurodegeneration, is understudied. Genetic variation in the LRRK2 gene affects risk for both familial and sporadic Parkinson's disease (PD). The leucine-rich repeat kinase 2 (LRRK2) protein is implicated in peripheral immune cell signaling, but the effects of an aging immune system on LRRK2 function remain unclear. We analyzed peritoneal macrophages from R1441C-Lrrk2 knock-in mice and...
Cytosolic <em>N6AMT1-</em>dependent translation supports mitochondrial RNA processing
Mitochondrial biogenesis relies on both the nuclear and mitochondrial genomes, and imbalance in their expression can lead to inborn errors of metabolism, inflammation, and aging. Here, we investigate N6AMT1, a nucleo-cytosolic methyltransferase that exhibits genetic codependency with mitochondria. We determine transcriptional and translational profiles of N6AMT1 and report that it is required for the cytosolic translation of TRMT10C (MRPP1) and PRORP (MRPP3), two subunits of the mitochondrial...
Multiomic profiling reveals timing of menopause predicts prefrontal cortex aging and cognitive function
A new case of dementia is diagnosed every 3 s. Beyond age, risk prediction of dementia is challenging. There is growing evidence of underlying processes that connect aging across organ systems and may provide insight for early detection, and there is a need to identify early biomarkers at an age when action can be taken to mitigate cognitive decline. We hypothesized that timing of menopause, a marker of ovarian aging, predicts brain age decades later. We used 2086 subjects with multiple "omics"...
Longitudinal accelerated brain age in mild cognitive impairment and Alzheimer's disease
INTRODUCTION: Brain age is a machine learning-derived estimate that captures lower brain volume. Previous studies have found that brain age is significantly higher in mild cognitive impairment and Alzheimer's disease (AD) compared to healthy controls. Few studies have investigated changes in brain age longitudinally in MCI and AD. We hypothesized that individuals with MCI and AD would show heightened brain age over time and across the lifespan. We also hypothesized that both MCI and AD would...
Spatial transcriptomic landscape unveils immunoglobin-associated senescence as a hallmark of aging
To systematically characterize the loss of tissue integrity and organ dysfunction resulting from aging, we produced an in-depth spatial transcriptomic profile of nine tissues in male mice during aging. We showed that senescence-sensitive spots (SSSs) colocalized with elevated entropy in organizational structure and that the aggregation of immunoglobulin-expressing cells is a characteristic feature of the microenvironment surrounding SSSs. Immunoglobulin G (IgG) accumulated across the aged...
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