Rewiring of Uric Acid Metabolism in the Intestine Promotes High-Altitude Hypoxia Adaptation in Humans.

Adaptation to high-altitude hypoxia is characterized by systemic and organ-specific metabolic changes. This study investigates whether intestinal metabolic rewiring is a contributing factor to hypoxia adaptation. We conducted a longitudinal analysis over 108 days, with seven time points, examining fecal metabolomic data from a cohort of 46 healthy male adults traveling from Chongqing (a.

Protein Restriction Effects on Healthspan and Lifespan in Drosophila melanogaster Are Additive With a Longevity-Promoting Diet.

Aging of the organism is associated diminished response to external stimuli including weakened immune function, resulting in diseases that impair health and lifespan. Several dietary restriction modalities have been reported to improve health and lifespan in different animal models, but it is unknown whether any of the lifespan-extending dietary treatments could be combined to achieve an additive effect. Here, we investigated the effects of halving amino acids components in the HUNTaa diet, a synthetic medium known to extend lifespan in Drosophila.

Scrutiny of genome-wide somatic mutation profiles in centenarians identifies the key genomic regions for human longevity.

Somatic mutations accumulate with age and are associated closely with human health, their characterization in longevity cohorts remains largely unknown. Here, by analyzing whole genome somatic mutation profiles in 73 centenarians and 51 younger controls in China, we found that centenarian genomes are characterized by a markedly skewed distribution of somatic mutations, with many genomic regions being specifically conserved but displaying a high function potential. This, together with the observed more efficient DNA repair ability in the long-lived individuals, supports the existence of key genomic regions for human survival during aging, with their integrity being of essential to human longevity.

Longevity-Associated Transcription Factor ATF7 Promotes Healthspan by Suppressing Cellular Senescence and Systematic Inflammation.

Aging is characterized by persistent low-grade systematic inflammation, which is largely responsible for the occurrence of various age-associated diseases. We and others have previously reported that long-lived people (such as centenarians) can delay the onset of or even escape certain major age-related diseases. Here, by screening blood transcriptome and inflammatory profiles, we found that long-lived individuals had a relatively lower inflammation level (IL6, TNFα), accompanied by up-regulation of activating transcription factor 7 (ATF7).

Multiple time-series expression trajectories imply dynamic functional changes during cellular senescence.

Cellular senescence is a dynamic process driven by epigenetic and genetic changes. Although some transcriptomic signatures of senescent cells have been discovered, how these senescence-related signals change over time remains largely unclear. Here, we profiled the transcriptome dynamics of human dermal fibroblast (HDF) cells in successive stages of growth from proliferation to senescence.

Specific Gain and Loss of Co-Expression Modules in Long-Lived Individuals Indicate a Role of circRNAs in Human Longevity.

Deep RNA sequencing of 164 blood samples collected from long-lived families was performed to investigate the expression patterns of circular RNAs (circRNAs). Unlike that observed in previous studies, circRNA expression in long-lived elderly individuals (98.3 ± 3.

Hepatic RACK1 deletion disturbs lipid and glucose homeostasis independently of insulin resistance.

Receptor for activated C kinase 1 (RACK1) is a versatile protein involved in multiple biological processes. In a previous study by Zhao et al., hepatic RACK1 deletion in mice led to an inhibition of autophagy, blocked autophagy-dependent lipolysis, and caused steatosis.

ETS1 acts as a regulator of human healthy aging via decreasing ribosomal activity.

Adaptation to reduced energy production during aging is a fundamental issue for maintaining healthspan or prolonging life span. Currently, however, the underlying mechanism in long-lived people remains poorly understood. Here, we analyzed transcriptomes of 185 long-lived individuals (LLIs) and 86 spouses of their children from two independent Chinese longevity cohorts and found that the ribosome pathway was significantly down-regulated in LLIs.

Telomere length is maternally inherited and associated with lipid metabolism in Chinese population.

Telomere is a unique DNA-protein complex which covers the ends of chromosomes to avoid end fusion and maintain the stability and integrity of chromosomes. Telomere length (TL) shortening has been linked to aging and various age-related diseases in humans. Here we recruited a total of 1031 Chinese individuals aged between 12 and 111 years, including 108 families with parents and their offspring.

Decreased miR-4512 Levels in Monocytes and Macrophages of Individuals With Systemic Lupus Erythematosus Contribute to Innate Immune Activation and Neutrsophil NETosis by Targeting TLR4 and CXCL2.

Objective: Systemic lupus erythematosus (SLE) is an autoimmune disease with complex etiology that is not yet entirely understood. We aimed to elucidate the mechanisms and therapeutic potential of microRNAs (miRNAs) in SLE in a Tibetan population.

Methods: Peripheral blood mononuclear cells from SLE patients (n = 5) and healthy controls (n = 5) were used for miRNA-mRNA co-sequencing to detect miRNAs related to immune abnormalities associated with SLE.

Senolytic targets and new strategies for clearing senescent cells.

Senescent cells (SCs) accumulate with age and cause various age-related diseases. Clearance of SCs by transgenic or pharmaceutical strategies has been demonstrated to delay aging, treat age-related diseases and extend healthspan. SCs are resistant to various stressors because they are protected from apoptosis by SC anti-apoptotic pathways (SCAPs).

Decoding the role of long noncoding RNAs in the healthy aging of centenarians.

Aging is the largest risk factor of major human diseases. Long noncoding RNAs (lncRNAs) as the key regulatory elements have shown a strong impact on multiple biological processes as well as human disease mechanisms. However, the roles of lncRNAs in aging/healthy aging processes remain largely unknown.

Glycerophosphodiester phosphodiesterase 1 (GDE1) acts as a potential tumor suppressor and is a novel therapeutic target for non-mucin-producing colon adenocarcinoma.

Colon adenocarcinoma (COAD) represents a major public health issue due to its high incidence and mortality. As different histological subtypes of COAD are related to various survival outcomes and different therapies, finding specific targets and treatments for different subtypes is one of the major demands of individual disease therapy. Interestingly, as these different subtypes show distinct metabolic profiles, it may be possible to find specific targets related to histological typing by targeting COAD metabolism.

Improved lipids, diastolic pressure and kidney function are potential contributors to familial longevity: a study on 60 Chinese centenarian families.

Centenarians are a good healthy aging model. Interestingly, centenarians' offspring are prone to achieve longevity. Here we recruited 60 longevity families and investigated the blood biochemical indexes of family members to seek candidate factors associated with familial longevity.