Aging & Longevity

Several major challenges, including an ageing population and declining workforce and the implementation of recent breakthrough therapies for Alzheimer disease, are prompting a necessary rethink of how people with neurodegenerative dementias are diagnosed and medically managed. Digital health technologies could play a pivotal part in this transformation, with new advances enabling the collection of millions of data points from a single individual. Possible applications include unobtrusive...

The clearance of senescent and altered red blood cells (RBCs) in the red pulp of the human spleen involves sequential processes of prefiltration, filtration, and postfiltration. While prior work has elucidated the mechanisms underlying the first two processes, biomechanical processes driving the postfiltration phagocytosis of RBCs retained at interendothelial slits (IES) are still poorly understood. We present here a unique computational model of macrophages to study the role of cell...

Cellular senescence is a stress-induced irreversible cell cycle arrest involved in tumor suppression and aging. Many stresses, such as telomere shortening and oncogene activation, induce senescence by damaging nuclear DNA. However, the mechanisms linking DNA damage to senescence remain unclear. Here, we show that DNA damage response (DDR) signaling to mitochondria triggers senescence. A genome-wide small interfering RNA screen implicated the outer mitochondrial transmembrane protein BNIP3 in...

Aging is an intricate process involving interactions among multiple factors, which is one of the main risks for chronic diseases, including Alzheimer's disease (AD). As a member of cysteine protease, cathepsin S (CTSS) has been implicated in inflammation across various diseases. Here, we investigated the role of neuronal CTSS in aging and AD started by examining CTSS expression in hippocampus neurons of aging mice and identified a significant increase, which was negatively correlated with...

DNA damage is a primary trigger for cellular senescence, which in turn causes organismal aging and is a promising target of anti-aging therapies. Most DNA damage occurs when DNA is fragile during DNA replication in S phase, but senescent cells maintain DNA damage long-after DNA replication has stopped. How senescent cells induce DNA damage and why senescent cells fail to repair damaged DNA remain open questions. Here, we combine reversible expression of the senescence-inducing CDK4/6 inhibitory...

Senescence and epigenetic alterations stand out as two well-characterized hallmarks of aging. When cells become senescent, they cease proliferation and release inflammatory molecules collectively termed the Senescence-Associated Secretory Phenotype (SASP). Senescence and SASP are implicated in numerous age-related diseases. Senescent cell nuclei undergo epigenetic reprogramming, which intricately regulates SASP expression. This review outlines the current understanding of how senescent cells...

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Senescent cells play a causative role in many diseases, and their elimination is a promising therapeutic strategy. Here, through a genome-wide CRISPR/Cas9 screen, we identify the gene PPIF, encoding the mitochondrial protein cyclophilin D (CypD), as a novel senolytic target. Cyclophilin D promotes the transient opening of the mitochondrial permeability transition pore (mPTP), which serves as a failsafe mechanism for calcium efflux. We show that senescent cells exhibit a high frequency of...

CONCLUSION: The results of the present study indicate a high prevalence of OCD among the older person. Hence, it is advised that greater attention be directed towards this issue by experts, authorities, and health policymakers.

This study evaluated longitudinal brain iron accumulation in older adults, its association with cognition, and the role of specific nutrients in mitigating iron accumulation. MRI-based, quantitative susceptibility mapping estimates of brain iron concentration were acquired from seventy-two healthy older adults (47 women, ages 60-86) at a baseline timepoint (TP1) and a follow-up timepoint (TP2) 2.5-3.0 years later. Dietary intake was evaluated at baseline using a validated questionnaire....

The prolyl hydroxylase domain-containing (PHD or EGL9-homologs) enzyme family is mainly known for its role in the cellular response to hypoxia. HIF-PH inhibitors can stabilize hypoxia-inducible factors (HIFs), activating transcriptional programs that promote processes such as angiogenesis and erythropoiesis to adapt to changes in oxygen levels. HIF-PH inhibitors have been clinically approved for treating several types of anaemia. While most discussions of the HIF-PH signalling axis focus on...

Telomeres, conserved DNA sequences at chromosome ends, naturally shorten with age, exacerbated by external factors like environmental challenges and reproduction. Birds, particularly psittacine, are gaining prominence as new aging models over the years because of their unique characteristics. This study explores erythrocyte telomere length (TL) and oxidative stress markers in plasma of long- and short-lived captive birds of the order Psittaciformes over four years. Long-lived birds consistently...

Parishin, a natural compound, has demonstrated significant potential in mitigating age-related phenotypes and improving outcomes in age-associated diseases. Given that aging is a major risk factor for numerous chronic conditions, including pulmonary fibrosis, we investigated parishin's effects on cellular senescence and lung health. In our study, we treated mouse lung epithelial cells with parishin and observed a reduction in cellular senescence markers alongside an upregulation of sirtuin 1...

Contest aims to improve molecular assays needed to test aging treatments.

Given its central role in immune aging, it is important to identify the regulators of thymic involution. While conventional programmed cell death has a fundamental role in thymocyte development, how cell death pathways contribute to thymic involution are unclear. In this study, we found that CD4^(+)CD8^(+) double-positive (DP) thymocytes acquired the characteristics of senescence in aged mice undergoing thymic involution, while expression of the m⁶A methyltransferase-like protein 3 (METTL3),...

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DNA storage has shown potential to transcend current silicon-based data storage technologies in storage density, longevity and energy consumption^(1-3). However, writing large-scale data directly into DNA sequences by de novo synthesis remains uneconomical in time and cost⁴. We present an alternative, parallel strategy that enables the writing of arbitrary data on DNA using premade nucleic acids. Through self-assembly guided enzymatic methylation, epigenetic modifications, as information bits,...

CONCLUSIONS: We demonstrated that frailty negatively affects the use of Social Support Act services, the use of community nursing services, medication use, and mortality risk. This study is the first to demonstrate the impact of frailty on Social Support Act services and community nursing services in the Netherlands. Findings emphasize the importance of frailty prevention for older people and public health policy.

CONCLUSIONS: IMUs could be useful tools for sarcopenia screening based on gait analysis, specifically when artificial intelligence is used to process the recorded data. However, more development and research in this field is needed to provide an effective screening tool for doctors and health systems.