Aging & Longevity

Cellular senescence, a hallmark of aging, reveals context-dependent phenotypes across multiple biological length scales. Despite its mechanistic importance, identifying and characterizing senescence across cell populations is challenging. Using primary dermal fibroblasts, we combined single-cell imaging, machine learning, several induced senescence conditions, and multiple protein biomarkers to define functional senescence subtypes. Single-cell morphology analysis revealed 11 distinct morphology...

Extracellular vesicles (EVs) are secreted by most cell types, transmitting crucial signaling molecules like proteins, small RNAs, and DNA. We previously demonstrated that EVs from murine and human mesenchymal stem cells (MSCs) functioned as senomorphics to suppress markers of senescence and the inflammatory senescence-associated secretory phenotype (SASP) in cell culture and in aged mice. Here we demonstrate that EVs from additional types of human adult stem cells and embryonic progenitor cells...

The mitochondrial translocator protein (TSPO) is a biomarker of inflammation associated with neurodegenerative diseases, widely regarded to be upregulated in the aging brain. Here we investigated the interaction between aging and TSPO immunomodulatory function in the mouse hippocampus, a region severely affected in Alzheimer's Disease (AD). Surprisingly, we found that TSPO levels were decreased in brain innate immune populations in aging. Aging resulted in a reversal of TSPO knockout...

Poor sleep is associated with worse cognitive function in older adults. However, nuanced associations between sleep and cognition might be masked by the multidimensional nature of sleep which requires multiple approaches (e.g., self-report and actigraphy) to gain meaningful insight. We investigated associations of sleep with cognition and hypothesized that the most consistent association would be between self-reported sleep duration and actigraphy-measured wake after sleep onset (WASO). We...

The amplification of molecular motion along length scales for macroscopic muscle-like functions, based on supramolecular polymers, provides attractive opportunities ranging from soft actuators to responsive biomedical materials. Taking the challenge to reveal dynamic assembly parameters governing muscle functions, we present the design of a photoswitch amphiphile based on an overcrowded alkene-derived core, and developed supramolecular artificial muscles. Going from molecular motor amphiphile...

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CONCLUSION: The proportion of poor SRH decreases with age despite a higher frequency of somatic health conditions. Associated factors varied across ages, indicating that physical factors more strongly influence SRH in younger-old adults, while psychosocial factors have a greater impact on SRH in older-old adults.

[This corrects the article DOI: 10.3389/fnagi.2020.00024.].

CONCLUSION: Research on fNIRS in elderly patients with MCI aims to provide an objective marker for MCI diagnosis. The current findings are mixed. However, these differences can be partly explained with the theoretical support from the interaction of cognitive load theory and scaffolding theory of aging and cognition, taking into account factors such as unspecified MCI subtypes, task difficulty, task design, monitoring duration, and population characteristics. Therefore, future studies should...

Multi-marker approaches are well suited for untangling the intrinsic complexity of aging and related conditions. Herein, we quantified (1) baseline concentrations of a panel of geroscience biomarkers pertaining to four biological domains (i.e., metabolism, inflammation, vascular/organ dysfunction and cellular senescence, and neurodegeneration) in individuals aged ≥60 years; (2) investigated linear and non-linear changes in biomarker levels over a 6-year period according to age and sex; and (3)...

Clonal haematopoiesis of indeterminate potential (CHIP) involves the gradual expansion of mutant pre-leukaemic haematopoietic cells, which increases with age and confers a risk for multiple diseases, including leukaemia and immune-related conditions¹. Although the absolute risk of leukaemic transformation in individuals with CHIP is very low, the strongest predictor of progression is the accumulation of mutant haematopoietic cells². Despite the known associations between CHIP and increased...

CONCLUSIONS: A coexistence of social isolation and loneliness was associated with a substantially lower likelihood of healthy aging among women. Our findings highlight the importance of social support in extending women's healthspan beyond the management of traditional risk factors.

CONCLUSION: IC trajectory among Chinese older adults is heterogeneous. Low IC with slow declining is associated with an increased risk of CVD incidence.

Biological aging is marked by a decline in resilience at the cellular and systemic levels, driving an exponential increase in mortality risk. Here, we evaluate several clinical and epigenetic clocks for their ability to predict mortality, demonstrating that clocks trained on survival and functional aging outperform those trained on chronological age. We present an enhanced clinical clock that predicts mortality more accurately and provides actionable insights for guiding personalized...

There are no appropriate mouse models to study the pathophysiology of spontaneous disc herniations in a wild-type setting. SM/J mice, a poor healer inbred strain, presented a high incidence of age-associated lumbar disc herniations with neurovascular innervations. Transcriptomic comparisons of the SM/J annulus fibrosus with human tissues showed shared pathways related to immune cell activation and inflammation. Notably, aged SM/J mice showed increased pain sensitization and neuroinflammation...

CONCLUSIONS: TI-CH increased the risk of disease recurrence or death among patients with NSCLC and the risk of death from any cause among patients with solid tumors. TI-CH remodeled the tumor immune microenvironment and accelerated tumor organoid growth, findings that support a role for an aging-related hematologic clonal proliferation in cancer evolution. (Funded by the Royal Society and others.).

Mitochondrial function is critical for neuronal activity and systemic metabolic adaptation. In this issue, Li et al. (https://doi.org/10.1083/jcb.202408050) identify TMBIM-2 as a key regulator of calcium dynamics, coordinating the neuronal-to-intestinal mitochondrial unfolded protein response (UPRmt), pathogen-induced aversive learning, and aging.

Neurodegenerative diseases are age-related disorders characterized by the cerebral accumulation of amyloidogenic proteins, and cellular senescence underlies their pathogenesis. Thus, it is necessary for preventing these diseases to remove toxic proteins, repair damaged neurons, and suppress cellular senescence. As a source for such prophylactic agents, we selected zizyphi spinosi semen (ZSS), a medicinal herb used in traditional Chinese medicine. Oral administration of ZSS hot water extract...

Epigenetic aging signatures provide insights into human aging, but traditional clocks rely on linear regression of DNA methylation levels, assuming linear trajectories. This study explores a non-parametric approach using 2D-kernel density estimation to determine epigenetic age. Our weighted model achieves similar predictive accuracy as conventional clocks and provides a variation score reflecting the inherent variability of age-related epigenetic changes within samples. This score is...

Human aging presents an evolutionary paradox: while aging rates remain constant, healthspan and lifespan vary widely. We address this conundrum via salutogenesis-the active production of health-through immune resilience (IR), the capacity to resist disease despite aging and inflammation. Analyzing ~17,500 individuals across lifespan stages and inflammatory challenges, we identified a core salutogenic mechanism: IR centered on TCF7, a conserved transcription factor maintaining T-cell stemness and...