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Category: genetics – Page 47

The ability to accurately quantify biological age could help monitor and control healthy aging. Epigenetic clocks have emerged as promising tools for estimating biological age, yet so far, most of these clocks have been developed from heterogeneous bulk tissues, and are thus composites of two aging processes, one reflecting the change of cell-type composition with age and another reflecting the aging of individual cell-types. There is thus a need to dissect and quantify these two components of epigenetic clocks, and to develop epigenetic clocks that can yield biological age estimates at cell-type resolution. Here we demonstrate that in blood and brain, approximately 35% of an epigenetic clock’s accuracy is driven by underlying shifts in lymphocyte and neuronal subsets, respectively. Using brain and liver tissue as prototypes, we build and validate neuron and hepatocyte specific DNA methylation clocks, and demonstrate that these cell-type specific clocks yield improved estimates of chronological age in the corresponding cell and tissue-types. We find that neuron and glia specific clocks display biological age acceleration in Alzheimer’s Disease with the effect being strongest for glia in the temporal lobe. The hepatocyte clock is found accelerated in liver under various pathological conditions. In contrast, non-cell-type specific clocks do not display biological age-acceleration, or only do so more marginally. In summary, this work highlights the importance of dissecting epigenetic clocks and quantifying biological age at cell-type resolution.

The authors have declared no competing interest.

The Illumina DNA methylation datasets analyzed here are all freely available from GEO (www.ncbi.nlm.nih.gov/geo).

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When we form a new memory, the brain undergoes physical and functional changes known collectively as a “memory trace.” A memory trace represents the specific patterns of activity and structural modifications of neurons that occur when a memory is formed and later recalled.

But how does the brain “decide” which neurons will be involved in a ? Studies have suggested that the inherent excitability of neurons plays a role, but the currently accepted view of learning has neglected to look inside the command center of the neuron itself, its nucleus. In the nucleus, there seems to be another dimension altogether that has gone unexplored: epigenetics.

Inside every cell of a given living organism, the genetic material encoded by the DNA is the same, yet the various cell types that make up the body, like , , or nerve cells each express a different set of genes. Epigenetics is the mechanism of how cells control such gene activity without changing the DNA sequence.

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I have a new essay out via the wonderful site Merion West. The article is based on some of my experimental writings at Oxford. I hope you’ll read and consider it. I’m highly worried life extension science isn’t moving forward fast enough!

“Sadly, biological humans are likely to be mortal for centuries more, unless a dramatic increase of both resources and life extension scientists are marshaled.”

Certain well-known gerontologists and longevity experts around the world believe that sometime in this century—probably in the next 15–50 years—medicine will likely overcome and cure most forms of disease, and even death itself. Billionaires such as Meta’s Mark Zuckerberg, Amazon’s Jeff Bezos, Alphabet’s Larry Page, and Oracle’s Larry Ellison have jumped on board, pledging billions of dollars to “conquering all disease by this century” and mortality altogether.

These business titans hope age reversal techniques via genetic editing therapies, stem cell rejuvenation, 3D bioprinting of organs, and the widespread creation of synthetic organs like artificial hearts could keep people indefinitely young and healthy. If biological human death from disease and aging are overcome, then only catastrophic accidental death—such as an airplane crash or incineration—can kill people. (Accidental death in this vein accounts for about seven percent of all deaths in the United States.)

Continue reading “When We’re Overly Optimistic about the Pace of Life Extension Research” | >

(CNN) — Regular aspirin use may keep the oncologist away, at least when it comes to colorectal cancer, according to a new study, and people with unhealthy lifestyles seemed to see the greatest benefit.

Colorectal cancer is the second most common cause of cancer death worldwide, predicted to cause more than 52,500 deaths in the US alone in 2023. About 153,020 people in the US were diagnosed with the condition in 2023, and it’s become much more prevalent among people under 55, with numbers more than doubling in this group from a decade ago, studies show.

The causes of colorectal cancer can be genetic, but certain lifestyle factors also seem to raise risk, including eating an unhealthy diet, not getting enough exercise, drinking alcohol, smoking and having a high body mass index.

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Yay face_with_colon_three

A 60-year-old man in Germany has become at least the seventh person with HIV to be announced free of the virus after receiving a stem-cell transplant1. But the man, who has been virus-free for close to six years, is only the second person to receive stem cells that are not resistant to the virus.

“I am quite surprised that it worked,” says Ravindra Gupta, a microbiologist at the University of Cambridge, UK, who led a team that treated one of the other people who is now free of HIV2,3. “It’s a big deal.”

The first person found to be HIV-free after a bone-marrow transplant to treat blood cancer4 was Timothy Ray Brown, who is known as the Berlin patient. Brown and a handful of others received special donor stem cells2,3. These carried a mutation in the gene that encodes a receptor called CCR5, which is used by most HIV virus strains to enter immune cells. To many scientists, these cases suggested that CCR5 was the best target for an HIV cure.

Continue reading “Seventh patient ‘cured’ of HIV: why scientists are excited” | >

At the mere flick of a magnetic field, mice engineered with nanoparticle-activated ‘switches’ inside their brains were driven to feed, socialize, and act like clucky new mothers in an experiment designed to test an innovative research tool.

While ’mind control’ animal experiments are far from new, they have generally relied on cumbersome electrodes tethering the subject to an external system, which not only requires invasive surgery but also sets limits on how freely the test subject can move about.

In what is claimed to be a breakthrough in neurology, researchers from the Institute for Basic Science (IBS) in Korea have developed a method for targeting pathways in the brain using a combination of genetics, nanoparticles, and magnetic fields.

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Aging is a universal experience, evident through changes like wrinkles and graying hair. However, aging goes beyond the surface; it begins within our cells. Over time, our cells gradually lose their ability to perform essential functions, leading to a decline that affects every part of our bodies, from our cognitive abilities to our immune health.

To understand how cellular changes lead to age-related disorders, Calico scientists are using advanced RNA sequencing to map molecular changes in individual cells over time in the roundworm, C. elegans. Much like mapping networks of roads and landscapes, we’re charting the complexities of our biology. These atlases uncover cell characteristics, functions, and interactions, providing deeper insights into how our bodies age.

In the early 1990s, Cynthia Kenyon, Vice President of Aging Research at Calico, and her former team at UCSF discovered genes in C. elegans that control lifespan; these genes, which influence IGF1 signaling, function similarly to extend lifespan in many other organisms, including mammals. The genetic similarities between this tiny worm and more complex animals make it a useful model for studying the aging process. In work published in Cell Reports last year, our researchers created a detailed map of gene activity in every cell of the body of C. elegans throughout its development, providing a comprehensive blueprint of its cellular diversity and functions. They found that aging is an organized process, not merely random deterioration. Each cell type follows its own aging path, with many activating cell-specific protective gene expression pathways, and with some cell types aging faster than others. Even within the same cell type, the rate of aging can vary.

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Summary: A new study reveals that the epigenetic state of neurons determines their role in memory formation. Neurons with open chromatin states are more likely to be recruited into memory traces, showing higher electrical activity during learning.

Researchers demonstrated that manipulating these epigenetic states in mice can enhance or impair learning. This discovery shifts the focus from synaptic plasticity to nuclear processes, offering potential new avenues for treating cognitive disorders.

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