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Category: life extension

Sprint or marathon? Aging muscle stem cells shift from rapid repair to long-term survival

Aging muscles heal more slowly after injury—a frustrating reality familiar to many older adults. A UCLA study conducted in mice reveals an unexpected cause: Stem cells in aged muscle accumulate higher levels of a protein that slows their ability to activate and repair tissue, but helps the cells survive longer in the harsh environment of aging tissue.

The findings, published today in the journal Science, suggest that some molecular changes associated with getting older may actually be protective adaptations rather than purely detrimental effects.

“This has led us to a new way of thinking about aging,” said Dr. Thomas Rando, senior author of the new study and director of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

Cellular survivorship bias as a mechanistic driver of muscle stem cell aging

Aging is characterized by a decline in the ability of tissue repair and regeneration after injury. In skeletal muscle, this decline is largely driven by impaired function of muscle stem cells (MuSCs) to efficiently contribute to muscle regeneration. We uncovered a cause of this aging-associated dysfunction: a cellular survivorship bias that prioritizes stem cell persistence at the expense of functionality. With age, MuSCs increased expression of a tumor suppressor, N-myc down-regulated gene 1 (NDRG1), which, by suppressing the mammalian target of rapamycin (mTOR) pathway, increased their long-term survival potential but at the cost of their ability to promptly activate and contribute to muscle regeneration. This delayed muscle regeneration with age may result from a trade-off that favors long-term stem cell survival over immediate regenerative capacity.

How a broken DNA repair tool accelerates aging

Although DNA is tightly packed and protected within the cell nucleus, it is constantly threatened by damage from normal metabolic processes or external stressors such as radiation or chemical substances. To counteract this, cells rely on an elaborate network of repair mechanisms. When these systems fail, DNA damage can accumulate, impair cellular function, and contribute to cancer, aging, and degenerative diseases.

One particularly severe form of DNA damage are the so-called DNA–protein crosslinks (DPCs), in which proteins become attached to DNA. DPCs can arise from alcohol consumption, exposure to substances such as formaldehyde or other aldehydes, or from errors made by enzymes involved in DNA replication and repair. Because DPCs can cause serious errors during cell division by stalling DNA replication, DNA–protein crosslinks pose a serious threat to genome integrity.

The enzyme SPRTN removes DPCs by cleaving the DNA-protein crosslinks. SPRTN malfunctions, for example as a result of mutations, may predispose individuals to developing bone deformities and liver cancer in their teenage years. This rare genetic disorder is known as Ruijs-Aalfs syndrome. Its underlying mechanism remains poorly understood, and there are no specific therapies.

Teaching NeuroImage: Miliary Perivascular Space Enhancement in Sepsis-Associated Posterior Reversible Encephalopathy Syndrome

Plants display a wide range of life spans and aging rates. Although dynamic changes to DNA methylation are a hallmark of aging in mammals, it is unclear whether similar molecular signatures reflect rates of aging and organism life span in plants. In this work, we show that the short-lived model plant Arabidopsis thaliana exhibits a loss of epigenetic integrity during aging, which causes DNA methylation decay and the expression of transposable elements. We show that the rate of epigenetic aging can be manipulated by extending or curtailing life span and that shoot apical meristems are protected from these epigenetic changes. We demonstrate that a program of transcriptional repression suppresses DNA methylation maintenance pathways during aging and that mutants of this program display a complete absence of epigenetic decay while physical aging remains unaffected.

DNA-Protein Crosslinks Explain Accelerated Aging in Progeria

In Ruijs-Aalfs progeria syndrome, patients experience accelerated aging and liver cancer.

Now, scientists showed that mutations in a certain gene prevent cells from repairing DNA damage during mitosis, triggering inflammatory immune responses that may fuel premature aging.

Read more.

Researchers have shown that harmful bonds between protein and DNA fuel immune attack in progeria. Pumping up a protein that cuts these bonds could prevent symptoms.

CLN3 mediates chloride efflux from lysosomes

Lysosomes degrade damaged organelles and macromolecules to recycle nutrient components. Lysosomal storage diseases (LSDs) are linked to mutations of genes encoding lysosomal proteins and may lead to age-related disorders, including neurodegenerative diseases. But, how lysosomal dysfunction contributes to neurodegenerative diseases is not clear yet…

The researchers identify CLN3 (ceroid lipofuscinosis, neuronal 3), linked to Batten disease as a conserved lysosomal protein that regulates lysosomal chloride homeostasis, pH, and protein degradation.

Curcumin analog C1 is a natural compound with anti-inflammatory properties could enhance CLN3 activity and improve lysosomal function by activating TFEB. sciencenewshighlights ScienceMission https://sciencemission.com/CLN3-n-chloride-efflux-n-lysosomes

Wang et al. identify CLN3 as a conserved lysosomal protein that regulates lysosomal chloride homeostasis, pH, and protein degradation. Transcription factor EB (TFEB) activation enhances CLN3 function, revealing the TFEB-CLN3 signaling axis as a promising therapeutic target for lysosomal storage disorders.

Physicists eye emerging technology for solar cells in outer space

Solar cells face significant challenges when deployed in outer space, where extremes in the environment decrease the efficiency and longevity they enjoy back on Earth. University of Toledo physicists are taking on these challenges at the Wright Center for Photovoltaics Innovation and Commercialization, in line with a large-scale research project supported by the Air Force Research Laboratory.

One recent advancement pertains to an emerging technology that utilizes antimony compounds as light-absorbing semiconductors. A group of UToledo faculty and students recently published a first-of-its-kind assessment exploring the promising characteristics of these antimony chalcogenide-based solar cells for space applications in the journal Solar RRL, which highlighted the work on its front cover.

“Antimony chalcogenide solar cells exhibit superior radiation robustness compared to the conventional technologies we’re deploying in space,” said Alisha Adhikari, a doctoral student in physics who co-led the team of undergraduate, graduate and faculty researchers at UToledo. “But they’ll need to become much more efficient before they become a competitive alternative for future space missions.”

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