Aging & Longevity

Why people age at different rates is a fundamental, unsolved problem in biology. We created a model that predicts an individual's age from physiological traits that change with age in the large UK Biobank dataset, such as blood pressure, lung function, strength, and stimulus-reaction time. The model predicted a person's age with best accuracy when it heavily weighted traits that together query multiple organ systems, arguing that most or all physiological systems (lung, heart, brain, etc.)...

Mutation, deletion, or silencing of genes encoding cellular metabolism factors occurs frequently in human malignancies. Neomorphic mutations in isocitrate dehydrogenases 1 and 2 (IDH1/2) promoting the production of R-2-hydroxyglutarate (R-2HG) instead of α-ketoglutarate (αKG) are recurrent in human brain cancers and constitute an early event in low-grade gliomagenesis. Due to its structural similarity with αKG, R-2HG acts as an inhibitor of αKG-dependent enzymes. These include the JUMONJI family...

Here, we investigated whether educational attainment influences the neurophysiological mechanisms underlying vigilance regulation, as reflected in resting-state eyes-closed electroencephalographic (rsEEG) rhythms, in patients with dementia due to Parkinson's (PDD) and Lewy body disease (DLB). Clinical, demographic, and rsEEG data were obtained from an international database, including PDD patients (N = 75), DLB patients (N = 50), and cognitively unimpaired older controls (Healthy; N = 54). Each...

The limited doubling capacity of human cells, known as replicative senescence or cellular senescence, is a major factor in cellular aging. This process is triggered by telomere erosion, which activates a p53-mediated DNA damage response (DDR) that halts cell proliferation. p53, a transcriptional regulator, responds to DNA damage by increasing the expression of the cyclin-dependent kinase inhibitor p21. p21 then arrests cells at specific stages of the cell cycle. Additionally, p53 upregulates...

In the United States, older adults who self-identify as Black have a disproportionately higher incidence of mobility disability compared to those who are White. Whether older adults who are Black also have lower fitness and mitochondrial energetics has not been adequately investigated. The study of muscle, mobility and aging (SOMMA) examined 879 participants aged ≥ 70 years old, including 116 who self-identified as Black. Mitochondrial respiration (Max OXPHOS) was measured in permeabilized...

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Early vascular aging plays a central role in chronic kidney disease (CKD), but its molecular causes remain unclear. Somatic mutations accumulate in various cells with age, yet their functional contribution to aging tissues is not well understood. Here we found progerin, the protein responsible for the premature aging disease Hutchinson-Gilford progeria syndrome, steadily recurring in vascular smooth muscle cells of patients with CKD. Notably, the most common progeria-causing mutation, LMNA...

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Cellular senescence, a major contributor to aging and age-related pathologies, is characterized by irreversible proliferative arrest and a disease-linked, proinflammatory profile known as the Senescence Associated Secretory Phenotype (SASP). A critical unanswered question is whether these properties are regulated by specific enhancer subsets, potentially licensing strategies that selectively block deleterious SASP components. Here, we identify two functionally distinct and independently...

CONCLUSIONS: Depression was prevalent among the oldest-old in India. Appropriate intervention strategies should be applied to prevent MMD among the oldest-old in India.

Advanced age is the most important risk factor for dementia. Measures of biological ageing such as DNA methylation age (DNAmAge) can give more information about the accumulation of age-related molecular damage in different organs than chronological age alone. Using post-mortem brain tissue from Swedish Twin Registry participants, we explored the relationship between lifestyle factors, dementia and DNAmAge measures from prefrontal cortex and cerebellum (n = 27 individuals) and paired blood...

Telomere shortening occurs in multiple tissues throughout aging. When telomeres become critically short, they trigger DNA-damage responses and p53 stabilization, leading to apoptosis or replicative senescence. In vitro, cells with short telomeres activate the cGAS-STING innate immune pathway resulting in type-I interferon-based inflammation and senescence. However, the consequences of these events for the organism are not yet understood. Here, we show that sting is responsible for premature...

CONCLUSIONS: Empty-nest older adults in the Chinese community show a desirable level of healthy ageing and psychological resilience, yet there is still room for improvement. Those who live with their spouses, have retirement pensions, engage regularly in social activities, and demonstrate strong psychological resilience tend to achieve a higher level of healthy ageing. Policies and strategies could focus on creating a more supportive environment, reducing health inequities among empty-nest older...

A strong association exists between exposure to life stressors and accelerated aging in humans and animal models. However, the molecular mechanisms that underlie the adverse effect of stress on aging remain poorly characterized, and there is a paucity of prognostic predictors of stress-induced disease outcomes and life expectancy. To address this gap, we developed mathematical models to predict remaining lifespan based on healthspan data across two independent cohorts which were part of a large...

Epigenetic drift, which is gradual age-related changes in DNA methylation patterns, plays a significant role in aging and age-related diseases. However, the relationship between exercise, epigenetics, and aging, and the molecular mechanisms underlying their interactions are poorly understood. Here, we investigated the relationship between cardiorespiratory fitness (CRF), epigenetic aging, and promoter methylation of individual genes across multiple organs in selectively bred low- and...

Brain precapillary sphincters, which are surrounded by contractile pericytes and are located at the junction of penetrating arterioles and first-order capillaries, can increase their diameter by ~ 30% in a few seconds during sensory stimulation, allowing for rapid control of capillary blood flow over a wide dynamic range. We hypothesized that these properties could help precapillary sphincters maintain the capillary blood flow and shield the downstream capillaries during surges in blood...

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CONCLUSION: Contrary to our hypothesis, older adults displayed more efficient heat-CPM, independent of chronic pain. Similarly, motor unit control was mostly influenced by age but not chronic knee pain. These findings suggest that age-related changes in pain modulation and motor unit behavior may play a greater role in neuromuscular function than the presence of chronic pain itself.

Tracking the envelope of speech in the brain is important for speech comprehension. Recent research suggests that acoustic background noise can enhance neural speech tracking, enabling the auditory system to robustly encode speech even under unfavorable conditions. Aging and hearing loss are associated with internal, neural noise in the auditory system, raising the question whether additional acoustic background noise enhances neural speech tracking in older adults. In the current...