Aging & Longevity

In many organisms, aging is a clear risk factor for chromosome missegregation, the main source of aneuploidy. Here, we report that old yeast cells lose chromosomes by partitioning them asymmetrically to their daughter cells together with the pre-existing (old) spindle pole body (SPB, centrosome equivalent in yeast). Strikingly, remodelling of the nuclear pore complex (NPC) and the displacement of its nuclear basket triggered these asymmetric chromosome segregation events. Simultaneously, nuclear...

CONCLUSIONS: Evidence shows a lack of structured long-term care policy in sub-Saharan Africa. Given the increasing demand for long-term care, there is an urgent need for policies that address factors affecting quality of life and ensure better care for older people in these facilities. A protocol for the scoping review was preregistered on the Open Science Framework Registry on 9th September 2023 (https://osf.io/xm8r5/).

Alpha-1 antitrypsin (AAT) deficiency in younger people is well characterized, but the effects of elevated AAT levels in older age are unclear. We examined the effect of elevated AAT levels and mortality in a longitudinal cohort of older adults, alongside high-sensitivity C-reactive protein (hs-CRP) levels. This post hoc analysis of the ASPirin in Reducing Events in the Elderly (ASPREE) trial included 11,879 adults aged ≥ 70 years without prior cardiovascular disease, dementia or life-limiting...

Social isolation and loneliness are growing public health concerns worldwide; however, the independent and combined associations of change in social isolation and loneliness with mortality are yet to be elucidated. This study aimed to investigate these associations among older adults. This cohort study used data from the Chinese Longitudinal Healthy Longevity Survey, which recruited participants from 2002 to 2011. A total of 8,956 participants aged 65 years and older were included. We used data...

Brown adipose tissue (BAT) protects against obesity, diabetes, and cardiovascular disease. During BAT activation, macroautophagy is inhibited, while chaperone-mediated autophagy (CMA) is induced, promoting thermogenic gene expression, adipokine release, oxidative activity, and lipolysis. Aging reduces BAT function and lowers levels of LAMP2A, the rate-limiting CMA component. Pharmacological CMA activation restores BAT activity in aged mice. To explore the CMA's role in BAT, we generated...

Genome instability is a major factor contributing to cellular senescence. The rRNA gene (rDNA), a repetitive sequence array, is a highly unstable region of the genome. In budding yeast, this instability induces senescence and shortens the lifespan. While the importance of rDNA stability in the aging process is well recognized, the mechanism driving rDNA instability in old cells remains unclear. Using effective methods to isolate old cells in budding yeast, our observations suggest that...

CONCLUSION: The results demonstrate a notable correlation between exposure to heavy metals, specifically lead and cadmium, and the incidence of frailty in U.S. adults aged over 20 years, with a more substantial impact observed in female participants.

Mitochondria play a crucial role in cellular energy metabolism and homeostasis and are strongly implicated in aging and age-related diseases. The outer mitochondrial membrane protein voltage-dependent anion channel (VDAC) plays multiple roles in mitochondrial homeostasis, including transport of metabolites, ATP, and Ca^(2+) Dysregulation of VDAC levels has been associated with cancer, neurodegeneration, metabolic disorders, and aging. Previously, we demonstrated that elevated VDAC-1 levels in...

Transparent conductive oxides (TCOs)-foundation of perovskite solar cells (PSCs)-have long been assumed to be stable, and thus their impact on device longevity is frequently overlooked. Herein, we unveil that fluorine doped tin oxide (FTO) suffers from instability under operational stress, exacerbating PSC stability issue. To address this issue, we propose a universal interface engineering strategy employing a scalable thermal evaporation followed by natural oxidation to form an atomically...

CONCLUSION: By analyzing the structure, strength, and interaction path between IC and FA, research has found that diseases are just a process of FA development. However, the source variable - patient's IC - has received less attention. This suggests that policymakers should not only focus on identifying a disease, but also on assessing, maintaining, and providing intervention before the disease. The authorities should also promote the implementation of people-centered rather than...

CONCLUSION: Green space mitigated the incidence of hypertension in older adults, particularly during extreme heat events. Urban greening could serve as a dual adaptation strategy against climate change and population aging.

CONCLUSIONS: Hence, supporting older adults who wish to attend religious services may be linked to better psychological well-being and mental health.

Fertility in women decreases with age, but the molecular basis for age-related, unexplained infertility remains elusive. Here, we reveal distinct transcriptome changes in oocytes and surrounding cumulus cells from women in their mid-thirties, as evidenced by notably increased transcription of ribosome genes. Additionally, meiosis genes and actin and cohesin components are downregulated in oocytes with age. Lysosomes and proteostasis are also disrupted in cumulus cells. Moreover, DNA...

In people living with HIV (PLWH), persistent viral replication and antiretroviral therapy (ART)-associated toxicity contribute to T cell exhaustion, characterised by significant metabolic reprogramming that negatively impacts cellular function and longevity. Understanding the metabolic dysregulation in exhausted T cells could unveil novel therapeutic strategies to rejuvenate immune responses in PLWH. This study investigated the prevalence and metabolic gene expression profiles of exhausted...

To verify whether DNA repair is regulated by FOXO3a, a tet-on flag-h-FOXO3a transgenic mice were used. RT-q-PCR and western blot analysis showed that the mRNA and protein levels of flag-h-FOXO3a, XRCC4, XPC, APE1 and MSH2 increased dose dependently by doxycycline. DNA repair activities like non-homologous end joining (NHEJ), nucleotide excision repair (NER), base excision repair (BER), mismatch repair (MMR) also increased in a doxycycline dose dependent manner. MEF (mouse embryonic fibroblast)...

This study critically reevaluates the utility of brain-age models within the context of detecting neurological and psychiatric disorders, challenging the conventional emphasis on maximizing chronological age prediction accuracy. Our analysis of T1 MRI data from 46,381 UK Biobank participants reveals that simpler machine learning models, and notably those with excessive regularization, demonstrate superior sensitivity to disease-relevant changes compared to their more complex counterparts,...

Decreased telomerase expression, telomere shortening, senescence-associated markers, and inflammation have all been independently observed in the ageing brain and associated with disease. However, causality between limited telomerase expression and brain senescence and neuro-inflammation in the natural ageing setting is yet to be established. Here, we address these questions using the zebrafish as an ageing model. Akin to humans, zebrafish display premature ageing and death in the absence of...

Decreased trabecular meshwork (TM) cellularity is a critical pathogenic cause of primary open-angle glaucoma, yet therapies to regenerate the decellularized TM are very limited. Induced pluripotent stem cell-derived TM-like cells (iPSC-TM) can efficiently restore aqueous humor outflow. Here, we conducted a multi-modal RNA sequencing analysis to characterize the molecular mechanisms underlying TM regeneration. Our clustering analysis identified a group of iPSC-derived alpha6 integrin-positive...

Trees are integral to ecosystems and hold considerable economic importance. Their exceptional longevity and modular structure also make them valuable models for studying the long-term accumulation of somatic mutations and epimutations in plants. Empirical evidence indicates that the annual rate of these stochastic events correlates negatively with generation time, suggesting that species with long lifespans have evolved mechanisms to mitigate the build-up of deleterious somatic variants. It has...

Aging research has primarily focused on adult aging clocks, leaving a critical gap in understanding a biological clock across the full life cycle, particularly during infancy and childhood. Here we introduce LifeClock, a biological clock model that predicts biological age across all life stages using routine electronic health records and laboratory test data. To enhance individualized predictions, we integrated virtual patient representations from 24,633,025 heterogeneous longitudinal clinical...