Lifeboat Foundation

How does the research conducted by Lige Leng at the Institute of Neuroscience of Xiamen University in China (I link it to you here)? It all starts with the study of the “inflamed brain”: many diseases of old age are associated with low-level chronic inflammation in the brain, organs, joints and circulatory system. A phenomenon sometimes called “inflammaging”.

You know it: over time all of our body’s repair systems deteriorate, our DNA and proteins accumulate damage, metabolism stumbles and cells stop doing their job. That’s life, beauty.

We’re all on our way to the exit, but research on worms, flies, mice and monkeys show that going at this speed isn’t inevitable. Diet and lifestyle changes (and, perhaps, upcoming anti-aging drugs) can curb decay and give us many more years of life, especially healthy life.

Continue reading “Discovered an aging ‘brake pedal’?” »

Several factors contribute to the development of inflamm-aging, including genetic susceptibility, visceral obesity, microbiota and gut permeability, cellular senescence, NLRP3 inflammasome activation, oxidative stress caused by mitochondrial dysfunction, immune cells dysregulation, and chronic infection (Ferrucci & Fabbri, 2018). The immune system becomes gradually dysregulated during aging, leading to elevated blood levels of pro-inflammatory mediators, such as TNFα, IL6, and C-reactive protein (Harris et al., 1999 ; Mooradian et al., 1991). Energy homeostasis also becomes dysregulated with aging, which results in the redistribution of subcutaneous fat to visceral regions and contributes to inflammation (Bouchard et al., 1993 ; Chumlea et al., 1989 ; Curtis et al., 2005). Metabolism-induced inflammation, also known as metaflammation, shares similarities with inflamm-aging, including the elevation of certain circulating pro-inflammatory cytokines (Prattichizzo et al., 2018). Therefore, the molecules that play a key role in the regulation of metabolic homeostasis potentially mediate the development of chronic inflammation during aging.

Forkhead box O1 (FOXO1) transcription factor has been indicated to be involved in the regulation of nutrient metabolism and energy homeostasis (Cheng et al., 2009 ; InSug et al., 2015 ; Matsumoto et al., 2007 ; Yang et al., 2019 ; Zhang et al., 2012). Deletion of hepatic Foxo1 improves glucose homeostasis in insulin resistant mice (Dong et al., 2008). FOXO1 inhibition by AS1842856 attenuates hepatic steatosis in diet-induced obesity mice (Ding et al., 2020). In mature macrophages, FOXO1 promotes inflammation through the activation of TLR4-and STAT6-mediated signaling pathways (Fan et al., 2010 ; Lee et al., 2022). In invertebrates, DAF-16, the Foxo homolog gene, mediates the effect of insulin/IGF signaling on lifespan (Ogg et al., 1997). Overexpression of FOXO in Drosophila and C.elegans increases their lifespan (Giannakou et al., 2004 ; Henderson & Johnson, 2001). However, studies in mammalians show that FOXO1 does not have a significant correlation with longevity (Chiba et al., 2009 ; Kleindorp et al., 2011). Considering the role of FOXO1 in regulating glucose metabolism and inflammation, we hypothesize that FOXO1 plays an important role in the regulation of aging-induced inflammation and dysregulation of glucose homeostasis.

Liver is an important metabolic organ that plays a key role in maintaining whole-body nutrient homeostasis by regulating energy metabolism, clearing xenobiotic and endobiotic, and synthesizing necessary molecules (Rui, 2014). As a result, aging-induced changes in liver contribute to systemic susceptibility to aging-related diseases. Different types of liver cells, including hepatocytes, endothelial cells, hepatic stellate cells (HSC), and macrophages, are all affected by the aging process (Hunt et al., 2019). However, most studies on liver aging focused on whole-liver tissue, which is mainly composed of parenchymal cells, hepatocytes. Thus, the effects of aging on liver nonparenchymal cells (NPCs) are less understood. In this study, we used bulk RNA-Seq and single-cell RNA (scRNA)-Seq technologies to analyze aging-induced changes, and the role of FOXO1 in aging-related processes in both whole-liver and individual liver cells, particularly liver macrophages. We found that insulin resistance, liver fat accumulation, liver inflammation, and systemic inflammation were significantly aggravated in old mice. Additionally, aging significantly increased pro-inflammatory response in Kupffer cells (KCs) and induced a functional quiescence in monocyte-derived macrophages (MDMs). FOXO1 activity was significantly enhanced in the livers of old mice and FOXO1 inhibition improved insulin resistance, hepatic steatosis, and inflammation in old mice. Furthermore, we found that FOXO1 inhibition attenuated aging-induced pro-inflammation in KCs and had a limited effect on aging-induced functional quiescence in MDMs. Taken together, this study indicates that FOXO1 plays an important role in the liver aging processes and suggests that FOXO1 is a potential therapeutic target for the treatment of aging-induced chronic diseases.

Stem cells can be classified based on their ability to specialize. Totipotent stem cells can become any tissue in the body, pluripotent stem cells can become any cell type except for a complete organ, and multipotent stem cells can only differentiate into specific tissue types.

Induced pluripotent stem cells (iPSCs) show promise in treating retinal degenerative diseases. They are created by reprogramming adult cells using Yamanaka factors, allowing them to revert to an embryonic state. These cells provide a virtually unlimited cell source for research and potential therapies.

Scientists are researching several diseases and drug development applications for these cells, highlighting the characteristics that make them an ideal therapy for macular degeneration.

More than 20 years ago, the human genome was first sequenced. While the first version was full of “holes” representing missing DNA sequences, the genome has been gradually improved in successive rounds. Each has increased the quality of the genome and, in so doing, resolved most of the blank spaces that prevented us from having a complete reading of our genetic material.

The fundamental difficulty researchers faced in reading the genome from end to end is the enormous number of repeated sequences that populate it. The 20,000 or so genes we humans have occupy barely 2% of the entire genome. The remaining 98% is essentially made up of these families of repeated sequences, mobile elements known as transposons and retrotransposons, and—to a lesser but functionally important extent— gene expression regulatory sequences. These function as switches that determine when and where genes are turned on and off.

In March 2022, a major revision of the genome was published in the journal Science. An international consortium of researchers known as “T2T” (telomere to telomere, which are the ends of chromosomes) used a novel strategy based a type of cell (CHM13) that retains only one copy of each chromosome.

A promising, more durable fuel cell design could help transform heavy-duty trucking and other clean fuel cell applications. Consisting of nanowires that are less susceptible to corrosion than other designs, the innovative electrode—the heart of a polymer electrolyte-membrane fuel cell—could usher in a new era for fuel cells, which use hydrogen as emission-free power for vehicles.

“In real-world terms, this means that we can have a more durable fuel cell that will provide high fuel economy over a longer lifetime,” said Jacob Spendelow, a scientist with the Los Alamos National Laboratory team that described its results in the journal Advanced Materials. “This work demonstrates that we can get rid of conventional carbon-based catalyst supports, eliminating the degradation problems associated with carbon corrosion, while still achieving high fuel cell performance.”

The improved durability makes this fuel cell a promising candidate for use in heavy-duty trucking applications, which require fuel cell lifetimes of more than 25,000 hours.

Dan Buettner’s Blue Zones research has transformed his lifestyle: He’s made physical activity a habit of his daily life and started eating more beans.

The incidence of cancer increases exponentially as we age. Unlike most age-related diseases, which generally cause cell and tissue degeneration and loss of function, cancer cells must acquire different, albeit aberrant, functions to progress to lethal disease. One link between age-related cancer and degeneration could be an inflammatory tissue environment driven by MTOR in senescent cells.

In her groundbreaking 2010 research perspective paper, The Senescence-Associated Secretory Phenotype: The Dark Side of Tumor Suppression, Dr. Judith Campisi from the Buck Institute for Research on Aging highlighted the tumor-promoting aspects of senescent cells. Campisi’s research showcased the significant ability of senescent cells to reshape the cellular landscape around them, crafting what scientists term the ‘microenvironment.’

Far from being an inert backdrop, this microenvironment serves as a dynamic stage upon which cells interact and potentially pave the way for disease progression, particularly cancer.

Scientists have recently reviewed the available literature to examine the critical roles played by mitochondria in maintaining homeostasis. The review summarized the involvement of mitochondria in age-related disease progression and highlighted its potential as a therapeutic target of these diseases. This review has been published in Experimental & Molecular Medicine.

Mitochondria is a cytoplasmic organelle in most eukaryotic cells and is enclosed by two phospholipid membranes: the inner mitochondrial membrane (IMM) and outer mitochondrial membrane (OMM). These membranes separate functionally compartmentalized structures, i.e., matrix and intermembrane space. Mitochondria contain a unique genetic code, mitochondrial DNA (mtDNA).

During evolution, most mitochondrial genes were lost or translocated to nuclei. However, genes that remained in mtDNA encode for essential translational apparatus, i.e., ribosomal RNAs and transfer RNAs. In addition, these genes also encode proteins that are key components of oxidative phosphorylation system (OXPHOS) complexes embedded in the IMM.

NIH-funded study suggests reducing exposure to airborne particulates may decrease dementia risk.

Higher rates of new cases of dementia in a population over time — known as incident dementia — are linked to long-term exposure to fine particulate matter (PM2.5) air pollution, especially from agriculture and open fires, according to a study funded by the National Institutes of Health and published in JAMA Internal Medicine. Scientists found that 15% of older adults developed incident dementia during the average follow-up of 10 years.

“As we experience the effects of air pollution from wildfires and other emissions locally and internationally, these findings contribute to the strong evidence needed to best inform health and policy decisions,” said Richard J. Hodes, M.D., director, National Institute on Aging (NIA), part of NIH. “These results are an example of effectively using federally funded research data to help address critical health risks.”