The researchers discovered that AP2A1 seemed to be responsible for switching cells between their “young” and “old” states—senescent cells were rejuvenated by the suppression of the protein, and younger cells aged by its overexpression.
The scientists also found that the AP2A1 was frequently in close proximity to another protein: integrin β1, which aids cells in binding to the collagen scaffold that envelops them. Both proteins, the researchers described, travel along stress fibers within cells.
The number of people suffering from osteoarthritis is expected to top 1 billion by 2050. The biggest risk factor for the prevalent, often painful, chronic joint disease is aging. And like aging, there is currently no way to stop it.
A discovery by scientists at Henry Ford Health + Michigan State University Health Sciences could pave the way for new breakthroughs in detecting and treating the disease. Their findings were recently published in Nature Communications.
“Our hope is that this discovery will one day allow doctors to catch the disease earlier and intervene before significant joint damage occurs,” said Shabana Amanda Ali, Ph.D., a Henry Ford Health assistant scientist and senior author of the paper. “Osteoarthritis is so complex and so heterogeneous that even with decades of research there hasn’t been a single therapeutic.”
Nicotinamide adenine dinucleotide (NAD) is a ubiquitous electron carrier essential for energy metabolism and post-translational modification of numerous regulatory proteins. Dysregulations of NAD metabolism are widely regarded as detrimental to health, with NAD depletion commonly implicated in aging. However, the extent to which cellular NAD concentration can decline without adverse consequences remains unclear. To investigate this, we generated a mouse model in which nicotinamide phosphoribosyltransferase (NAMPT)-mediated NAD+ biosynthesis was disrupted in adult skeletal muscle. The intervention resulted in an 85% reduction in muscle NAD+ abundance while maintaining tissue integrity and functionality, as demonstrated by preserved muscle morphology, contractility, and exercise tolerance. This absence of functional impairments was further supported by intact mitochondrial respiratory capacity and unaltered muscle transcriptomic and proteomic profiles. Furthermore, lifelong NAD depletion did not accelerate muscle aging or impair whole-body metabolism. Collectively, these findings suggest that NAD depletion does not contribute to age-related decline in skeletal muscle function.
#Aging #Longevity aging and longevity.
NAD depletion in skeletal muscle does not impair tissue integrity and function or accelerate aging, as shown in a mouse model with an 85% decrease in muscle NAD+ levels. Muscle structure, metabolism, and mitochondrial function remain unaffected, suggesting that NAD depletion does not drive age-related muscle decline.
Ambrosi and colleagues profile human skeletal stem cells (hSSCs) across ten fetal skeletal sites and from patients throughout adulthood, identifying, mapping, and functionally testing four distinct hSSC subtypes. Skeletal aging and disease are characterized by a dominant fibrogenic hSSC variant, but targeting defined gene regulatory networks reinstates functional hSSC diversity.
In our Founder Interview series, we highlight the brightest minds in preventive health, wellness, and longevity. In Episode 6, we’re honored to feature Dr. Emil Kenziorra, founder and CEO at Tomorrow Biostasis —one of the world-leading human cryopreservation experts.
Tell us a little about yourself and your current venture
Doctor and researcher by training, entrepreneur by trade. Longevity has always been my motivation, with a focus on maximal life span extension. I’m running Tomorrow.bio and the non-profit European Biostasis Foundation to push human cryopreservation forward.
Scientists at the University of East Anglia (UEA) have developed a new way of uncovering the “true age” of a heart using MRI.
Research accepted for publication European Heart Journal Open shows how an MRI scan can reveal your heart’s functional age—and how unhealthy lifestyles can dramatically accelerate this figure. The paper is titled “Cardiac MRI Markers of Ageing: A Multicentre, Cross-sectional Cohort Study.”
It is hoped that the findings could transform how heart disease is diagnosed—offering a lifeline to millions by catching problems before they become deadly.
The duplication and division of cells is critical to keeping all multicellular organisms alive. But the opposite process is equally important: cell death. Controlled death of cells, or programmed cell death, is also necessary for the proper development and function of the body. It has also been a focus of researchers developing treatments for cancer by finding ways to activate the cell death of cancer cells themselves.
Ferroptosis is a recently discovered form of programmed cell death and has been a promising target for the development of cancer treatments. It is mediated by iron molecules, with the cell dying through the degradation of the phospholipid bilayer by oxidation, a process called lipid peroxidation. However, recent studies have shown that certain cancer cells are less susceptible to ferroptosis, raising concerns that this resistance could pose a barrier to future therapeutics.
In a paper published in Nature Communications, researchers from Kyushu University, using cultured cells and mice, found that the lipid peroxidation of the lysosomes—the organelle responsible for degrading and recycling molecules in a cell—plays a critical role in the execution of ferroptosis.