Aging & Longevity
Resilience to mid-to-late-life depression as a risk factor for Alzheimer's disease: Physiological factors and the role of neuroimaging
Depression and Alzheimer's Disease (AD) are both diagnosed in women twice as often as in men. Moreover, a history of untreated depression confers a 2-to-5-fold increase in the risk of developing dementia. Finally, biological factors such as sex differences in immune response increase rates of depressive pathology among women. Importantly, the prevalence of mid-to-late-life depression (MLD) worldwide and its misdiagnosis due to clinical overlap with AD hinder accurate assessment and timely...
A comparison of deep multiomics profiles across ethnicity, geography, and age
Despite extensive research, molecular differences in human populations and the influence of ancestry, age, geography, and diet are poorly understood. We performed comprehensive multiomics profiling (including genomics, transcriptomics, proteomics, metabolomics, lipidomics, metallomics, glycomics, and microbiomics) on samples from 322 healthy individuals of European, East Asian, and South Asian ancestry across multiple continents. We identified ethnicity-associated molecular features linked to...
An optimized method to visualize lipid droplets in mouse brain tissue
Lipid droplets (LDs) are lipid-storage organelles that have gained interest in neurodegenerative diseases, yet their physiological role in the brain is not fully understood. Classical LD detection using lipophilic dyes like BODIPY 493/503 (BD493) or antibodies against LD coat proteins typically reveals few LDs in healthy brain tissue. In contrast, our recently developed endogenous LD-reporter mouse showed numerous LDs in the developing and adult brain without staining. To understand this...
Cellular Senescence as a Systems-Level Driver of Cardiovascular Ageing
Cellular senescence is increasingly recognized as a fundamental driver of cardiovascular ageing; however, its molecular heterogeneity, cell-type specificity, and translational relevance remain incompletely understood. Accumulating evidence indicates that cardiovascular senescence is not a uniform or cell-autonomous process, but rather an emergent property of interacting endothelial, vascular smooth muscle, immune, and stromal cell networks shaped by metabolic stress, immune dysregulation, and...
Metal ions in aging and ocular diseases: biology, pathophysiology, and therapeutic strategies
Metal ions are indispensable for sustaining normal cellular functions and preserving tissue integrity, as they participate in enzymatic catalysis, signal transduction, and antioxidant defense. However, dysregulation of metal ion homeostasis, particularly during aging, disrupts cellular balance and significantly drives the development and progression of age-related ocular diseases, including age-related macular degeneration, glaucoma, diabetic retinopathy, and cataracts. Specifically, metal ions...
Enamel-inspired composite with robust mechanical properties and self-healing capability
Echoing the regenerative powers of living organisms, self-healing materials can recover from damage, extending their lifespan and enhancing dependability, thus holding broad applications promise across diverse fields, including biological tissue engineering, soft robotics, flexible electronics, and automotive industries. Nonetheless, self-healing materials typically suffer from poor mechanical properties, a limitation stemming from the inherent trade-off between mechanical robustness and...
SIRT6 overexpression counteracts chromatin aging in the male murine liver
Aging is associated with detrimental changes in chromatin structure and gene expression, contributing to inflammation, metabolic decline and tissue dysfunction. SIRT6, a histone deacetylase, plays a key role in maintaining chromatin integrity and promoting longevity. Our multi-omics approach, combining ATAC-seq, methylome and RNA-seq shows that aging leads to increased chromatin accessibility in the male murine liver, accompanied by upregulation of inflammation and downregulation of metabolic...
Linking the exposome to the brain-behaviour phenotype
A range of environmental, lifestyle and biological exposures across the lifespan - varying in timing, duration and intensity - interact with genetic factors to shape an individual's neurocognitive phenotype. By referring to the totality of exposures that an individual has experienced in their life so far, the exposome offers a valuable concept to better understand interindividual variability in not only brain-behaviour phenotype but also vulnerability and resilience to brain diseases. Numerous...
Immune cells in the blood drive cognitive ageing - blocking them improves memory
No abstract
Human whole-blood NAD<sup>+</sup> levels do not vary with age or lifestyle interventions
Nicotinamide adenine dinucleotide (NAD^(+)) levels in blood and tissues are widely proposed to decline with age, yet evidence in human blood is inconsistent. Using a rigorously validated ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry system that accounts for real-world analytical variability, we quantify NAD^(+) across seven independent human cohorts. We find that whole-blood NAD^(+) levels remain remarkably stable with age and across lifestyle...
Whole-blood NAD(+) levels do not reflect healthy ageing
No abstract
Reduced ULK1 links impaired autophagy and mitophagy to Alzheimer's disease pathology
ULK1 (Atg1) initiates macroautophagy and mitophagy, which support neuronal growth and survival, yet how this pathway is disrupted in aging and Alzheimer's disease (AD) remains unclear. Here we report reduced ULK1 in serum and cerebrospinal fluid during aging in cognitively unimpaired participants from the COGNORM study (n = 75) and in patients with AD from the NorCog Memory Clinic Cohort (n = 316). In AD mice, ULK1 overexpression stimulates autophagic flux, reduces AD pathology and delays...
Glutamine-driven reductive TCA cycle metabolism supports aged muscle stem cell function via de novo lipogenesis
Sarcopenia and the age-related decline in muscular strength and regenerative capacity contribute directly to loss of autonomy, greater risk for hospitalization and healthcare utilization. One contributing cellular phenotype associated with skeletal muscle aging is a loss in the function and number of resident muscle stem cells (MuSCs) or satellite cells. MuSC activation leads to dramatic changes in cellular architecture and metabolic reprogramming, including both mitochondrial biogenesis and...
Social support and associated factors among community-dwelling older adults in Singapore - a cross-sectional study
CONCLUSIONS: Social support levels were comparable to international findings. Strategies are needed to enhance emotional support as scores were lowest in this domain. Frailty was associated with lower support, reinforcing a need to focus on support for this at-risk population. The positive association between community resource utilisation and social support despite low utilisation represents an area of untapped opportunity.
Malnutrition is associated with lower oxygen radical absorbance capacity in older adults: a cross-sectional study
BACKGROUND: Reactive oxygen species may play a significant role in the aging process, and there is currently limited research that assesses the correlation between oxygen radical absorbance capacity (ORAC) and malnutrition.
Association between physical resilience and self-perceptions of aging among Chinese community-dwelling older adults: a cross-sectional study
CONCLUSIONS: This study highlights the crucial associations of aging awareness and negative results with PR. Therefore, community medical workers can promote the correct understanding of aging and achieve positive aging by enhancing the physical resilience of the elderly in the community.
Reframing Expectations about aging - Physical Activity and Inclusive Reappraisal (RE-PAIR): Protocol of a randomized intervention promoting positive self-perceptions of aging and physical activity in older couples
CONCLUSION: This project will provide evidence on whether targeting couples could enhance/facilitate promotion of positive self-perceptions of aging and physical activity in older age.
Brain senescence drives sarcopenia-like transcriptomic remodeling in skeletal muscle
Aging is accompanied by a progressive decline in skeletal muscle mass and function, culminating in sarcopenia, a major contributor to frailty, disability, and mortality in older adults. While skeletal muscle aging has traditionally been attributed to cell-autonomous and local tissue mechanisms, increasing evidence suggests that systemic, cell non-autonomous processes play a central role in coordinating aging across organs. The brain, particularly the hypothalamus, has emerged as a key regulator...
A Person-Centered Exploration of Mental and Cognitive Health Risk Profiles in Community-Dwelling Older Adults
IntroductionThis study extends prior work by identifying multidimensional profiles of co-occurring mental health and cognitive symptoms that better reflect the complexity of aging and identify high-risk subgroups with more severe symptom profiles.MethodsThis secondary analysis used Wave II data from the National Social Life, Health, and Aging Project (NSHAP). Latent profile analysis was conducted to identify distinct symptom profiles and examine associated sociodemographic, clinical, and...
Beyond survival: Redefining successful aging in the era of medical complexity
A common misconception is that increasing longevity reflects slower aging. Instead, most longevity gain comes from medical advances that allow survival with disease, rather than changes to the biology of aging itself, challenging how we study aging and health.
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