Aging & Longevity
Phenotypic upregulation of hexocylceramides and ether-linked phosphocholines as markers of human extreme longevity
Centenarians and their relatives possess a notable survival advantage, with higher longevity and reduced susceptibility to major age-related diseases. To date, characteristic omics profiles of centenarians have been described, demonstrating that these individuals with exceptional longevity regulate their metabolism to adapt and incorporate more resilient biomolecules into their cells. Among these adaptations, the lipidomic profile stands out. However, it has not yet been determined whether this...
Estradiol deficiency as a consequence of aging contributes to the depletion of the satellite cell pool in female mice
The effects of aging on the satellite cell pool have primarily been studied in male mice, where the role of cell-intrinsic versus environmental changes on satellite cell function remains contentious. Estradiol is necessary for maintenance of satellite cell pool size in adult female mice-here we investigate the hypothesis that in females, estradiol is a major environmental driver of age-associated effects on satellite cells. In 24-26 month-old ovarian senescent mice, we find the satellite cell...
Similarities and differences in the gene expression signatures of physiological age versus future lifespan
Across all taxa of life, individuals within a species exhibit variable lifespans. Differences in genotype or environment are not sufficient to explain this variance, as even isogenic Caenorhabditis elegans nematodes reared under uniform conditions show significant variability in lifespan. To investigate this phenomenon, we used lifespan-predictive biomarkers to isolate, at mid-adulthood, prospectively long- and short-lived individuals from an otherwise identical population. We selected two...
Relationships of functional connectivity of motor cortex, primary somatosensory cortex, and cerebellum to balance performance in middle-aged and older adults
Connectivity of somatosensory cortex (S1) and cerebellum with the motor cortex (M1) is critical for balance control. While both S1-M1 and cerebellar-M1 connections are affected with aging, the implications of altered connectivity for balance control are not known. We investigated the relationship between S1-M1 and cerebellar-M1 connectivity and standing balance in middle-aged and older adults. Our secondary objective was to investigate how cognition affected the relationship between connectivity...
Locus coeruleus MRI contrast, cerebral perfusion, and plasma Alzheimer's disease biomarkers in older adults
The locus coeruleus (LC) is among the first brain structures impacted by Alzheimer's disease (AD), and noradrenergic denervation may contribute to early neurovascular dysfunction in AD. Mechanistic links between the LC and cerebral perfusion have been demonstrated in rodents, but there have been no similar studies in aging humans. Community-dwelling older adults with no history of stroke or dementia (N=66) underwent structural (T1-MPRAGE; T1-FSE) and perfusion (resting pCASL) MRI. Plasma AD...
Genetic risk factors for late-onset Alzheimer's disease drive senescence in female tauopathy mice
Carling et al. report that late-onset Alzheimer's disease (LOAD) risk alleles drive cellular senescence, a hallmark of aging, in a tau- and sex-dependent manner. Mechanistic insights into interactions among genetic risk, biological aging, and sex differences in LOAD are presented.
The senotherapeutic potential of phytochemicals for age-related intestinal disease
During the last few decades, life expectancy has increased worldwide along with the prevalence of several age-related diseases. Among aging pathways, cellular senescence and chronic inflammation (or "inflammaging") appear to be connected to gut homeostasis and dysbiosis of the microbiome. Cellular senescence is a state of essentially irreversible cell cycle arrest that occurs in response to stress. Although senescent cells (SC) remain metabolically active, they do not proliferate and can secrete...
Association of Indoor Environment With the Intention to Enter Nursing Homes Among Older Adults With Functional Limitations in Japan
CONCLUSIONS AND IMPLICATIONS: The results of this study revealed that better indoor environments in terms of cooling, heating, acoustics, odor, and lighting could potentially delay nursing home admission. Integrating the assessments of these indoor environmental factors into policy frameworks may enhance the effectiveness of long-term care strategies and promote aging.
Leaky gut in systemic inflammation: exploring the link between gastrointestinal disorders and age-related diseases
Global average life expectancy has steadily increased over the last several decades and is projected to reach ~ 77 years by 2050. As it stands, the number of people > 60 years currently outnumbers children younger than 5 years, and by 2050, it is anticipated that the global population of people aged > 60 years will double, surpassing 2.1 billion. This demographic shift in our population is expected to have substantial consequences on health services globally due to the disease burden associated...
The dynamics of hematopoiesis over the human lifespan
Over a lifetime, hematopoietic stem cells (HSCs) adjust their lineage output to support age-aligned physiology. In model organisms, stereotypic waves of hematopoiesis have been observed corresponding to defined age-biased HSC hallmarks. However, how the properties of hematopoietic stem and progenitor cells change over the human lifespan remains unclear. To address this gap, we profiled individual transcriptome states of human hematopoietic stem and progenitor cells spanning gestation, maturation...
Accelerated biological aging, healthy behaviors, and genetic susceptibility with incidence of stroke and its subtypes: A prospective cohort study
Stroke risk increases with chronological age, but the relationship with biological age (BA) acceleration is poorly understood. We aimed to examine the association between BA acceleration and incident stroke and its subtypes, explore the modifying effects on genetic susceptibility, and assess how BA acceleration mediates the effect of behavior score. We studied 253,932 UK Biobank participants and computed two BA measures (Klemera-Doubal Method [KDM], Phenotypic Age [PhenoAge]), with BA...
Ageing limits stemness and tumorigenesis by reprogramming iron homeostasis
Ageing is associated with a decline in the number and fitness of adult stem cells^(1,2). Ageing-associated loss of stemness is posited to suppress tumorigenesis^(3,4), but this hypothesis has not been tested in vivo. Here we use physiologically aged autochthonous genetically engineered^(5,6) mouse models and primary cells^(5,6) to demonstrate that ageing suppresses lung cancer initiation and progression by degrading the stemness of the alveolar cell of origin. This phenotype is underpinned by...
Nicotinamide mononucleotide suppresses cellular senescence and increases aquaporin 5 expression in the submandibular gland of aged male mice to ameliorate aging-related dry mouth
Dry mouth results from decreased saliva secretion due to aging or drug side effects. Decreased saliva secretion causes dryness in the oral cavity that makes swallowing difficult and increases the risk of aspiration pneumonia. There are few fundamental treatments for dry mouth. Here we investigated whether treatment of old mice with nicotinamide mononucleotide (NMN) improved factors associated with dry mouth. Young (16-week-old) and old (113-week-old) male mice were treated subcutaneously with...
Ageing of stem cells reduces their capacity to form tumours
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Daily briefing: What is ageing? Even gerontologists don't agree
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Why breast cancer treatments might work best just after your period
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Study on the age-period-cohort effects of cognitive abilities among older Chinese adults based on the cognitive reserve hypothesis
CONCLUSIONS: The cognitive reserve hypothesis supports the significance of the majority of identified influencing factors. Cognitive abilities demonstrate an accelerating decline with increasing age, following an evolutionary trajectory consistent with physiological principles among older Chinese adults. Since 2008, cognitive abilities have shown a monotonic increasing trend annually, further validating the Flynn effect in this population. The cognitive abilities of the six earlier-born cohorts...
<em>Hydra</em> has mammal-like mutation rates facilitating fast adaptation despite its nonaging phenotype
Growing evidence suggests that somatic mutations may be a major cause of the aging process. However, it remains to be tested whether the predictions of the theory also apply to species with longer life spans than humans. Hydra is a genus of freshwater polyps with remarkable regeneration abilities and a potentially unlimited life span under laboratory conditions. By genome sequencing of single cells and whole animals, we found that the mutation rates in Hydra's stem cells are even slightly higher...
Women and aging
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An online driving decision aid for older drivers reduces ambivalence and regret about driving decisions: Randomized trial
CONCLUSIONS: In older drivers, the Healthwise® DDA reduced uncertainty and regret about driving decisions during longitudinal follow-up, without adversely affecting community mobility or crash risk. Use of DDAs in clinical and other settings may reduce the distress older adults often experience when making decisions about driving cessation.
Aging and Longevity: Latest results from PubMed
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