Lifeboat Foundation

The latest from Calico. A bit technical.

Reprogramming of ordinary somatic cells into induced pluripotent stem cells (iPSCs) was initially thought to be a way to obtain all of the patient matched cells needed for tissue engineering or cell therapies. A great deal of work has gone towards realizing that goal over the past fifteen years or so; the research community isn’t there yet, but meaningful progress has taken place. Of late, another line of work has emerged, in that it might be possible to use partial reprogramming as a basis for therapy, delivering reprogramming factors into animals and humans in order to improve tissue function, without turning large numbers of somatic cells into iPSCs and thus risking cancer or loss of tissue structure and function.

Reprogramming triggers some of the same mechanisms of rejuvenation that operate in the developing embryo, removing epigenetic marks characteristic of aged tissues, and restoring youthful mitochondrial function. It cannot do much for forms of damage such as mutations to nuclear DNA or buildup of resilient metabolic waste, but the present feeling is there is nonetheless enough of a potential benefit to make it worth developing this approach to treatments for aging. Some groups have shown that partial reprogramming — via transient expression of reprogramming factors — can reverse functional losses in cells from aged tissues without making those cells lose their differentiated type. But this is a complicated business. Tissues are made up of many cell types, all of which can need subtly different approaches to safe reprogramming.

Today’s open access preprint is illustrative of the amount of work that lies ahead when it comes to the exploration of in vivo reprogramming. Different cell types behave quite differently, will require different recipes and approaches to reprogramming, different times of exposure, and so forth. It makes it very hard to envisage a near term therapy that operates much like present day gene therapies, meaning one vector and one cargo, as most tissues are comprised of many different cell types all mixed in together. On the other hand, the evidence to date, including that in the paper here, suggests that there are ways to create the desired rejuvenation of epigenetic patterns and mitochondrial function without the risk of somatic cells dedifferentiating into stem cells.

Continue reading “A Great Deal of Work Lies Ahead in the Development of In Vivo Reprogramming as a Therapy” »

Ed Whitlock remains at the forefront among older athletes who have led scientists to reassess the possibilities of aging and performance.

Aging is associated with an overall decline in health and increased frailty, and is a major risk factor for multiple chronic diseases. Frailty syndrome, characterized by weakness, fatigue and low physical activity, affects more than 30% of the elderly population. Increasing our understanding of the mechanisms underlying the aging process is a top priority to facilitate the development of interventions that will lead to the preservation of health and improvements on survival and lifespan.

Cumulative evidence suggests that diet and metabolism are key targetable regulators of healthy lifespan. Prof. Haim Cohen, Director of the Sagol Healthy Human Longevity Center at Bar-Ilan University, focuses much of his research on the SIRT6 protein that is involved in regulating many biological processes, such as aging, obesity, and insulin resistance.

In a study just published in the journal Nature Communications, an international team led by Cohen and his Ph.D. student Asael Roichman—together with Prof. Rafael de Cabo, of the National Institute on Aging at the National Institutes of Health, Prof. Manuel Serrani, of the Institute for Research in Biomedicine in Barcelona, and Prof. Eyal Gottlieb from the Technion—report that transgenic mice express high levels of the SIRT6 gene, and show that their life expectancy can be increased by an average of 30% in both males and females. Translated into human terms this means that a 90-year-old could live until nearly 120!

A new discovery could lead to new drugs for faster repairing muscles after injury — or rebuilding muscle mass lost during the normal aging process.

Researchers at the Salk Institute have uncovered a mechanism by which stem cells can help regenerate muscles. The discovery could provide a new drug target for repairing muscles after injury or rebuilding muscle mass lost during the normal aging process.

The breakthrough started with a set of proteins called Yamanaka factors, which have long been studied as a key part of stem cell therapy. These factors are used to convert regular cells – most commonly skin cells – into what are known as induced pluripotent stem cells (iPS), which can then go on to differentiate into a variety of other cell types. That in turn helps regenerate tissue. But exactly how the Yamanaka factors worked their magic remained a mystery.

Continue reading “Scientists discover how stem cells trigger muscle regeneration” »

Hydraulic Instability Decides Who’s to Die and Who’s to Live

In many species including humans, the cells responsible for reproduction, the germ cells, are often highly interconnected and share their cytoplasm. In the hermaphrodite nematode Caenorhabditis elegans, up to 500 germ cells are connected to each other in the gonad, the tissue that produces eggs and sperm. These cells are arranged around a central cytoplasmic “corridor” and exchange cytoplasmic material fostering cell growth, and ultimately produce oocytes ready to be fertilized.

In past studies, researchers have found that C. elegans gonads generate more germ cells than needed and that only half of them grow to become oocytes, while the rest shrinks and die by physiological apoptosis, a programmed cell death that occurs in multicellular organisms. Now, scientists from the Biotechnology Center of the TU Dresden (BIOTEC), the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), the Cluster of Excellence Physics of Life (PoL) at the TU Dresden, the Max Planck Institute for the Physics of Complex Systems (MPI-PKS), the Flatiron Institute, NY, and the University of California, Berkeley, found evidence to answer the question of what triggers this cell fate decision between life and death in the germline.

With 2700 locations across 10000 U.S. communities, YMCA is becoming a major hub for healthy living — From vaccinations and diabetes prevention programs, to healthy aging and wellness — Siva Balu, VP/Chief Information Officer — The Y of the U.S.A.

Mr. Siva Balu is Vice President and Chief Information Officer of YMCA of the U.S. (Y-USA), where he is working to rethink and reorganize the work of the organization’s information technology strategy to meet the changing needs of Y-USA and Ys throughout the country.

Continue reading “Siva Balu — VP / Chief Information Officer — YMCA of the U.S.A. — People, Potential, & Purpose” »

In many species including humans, the cells responsible for reproduction, the germ cells, are often highly interconnected and share their cytoplasm. In the hermaphrodite nematode Caenorhabditis elegans, up to 500 germ cells are connected to each other in the gonad, the tissue that produces eggs and sperm. These cells are arranged around a central cytoplasmic “corridor” and exchange cytoplasmic material fostering cell growth, and ultimately produce oocytes ready to be fertilized.

In past studies, researchers have found that C. elegans gonads generate more germ cells than needed and that only half of them grow to become oocytes, while the rest shrink and die by physiological apoptosis, a programmed cell death that occurs in multicellular organisms. Now, scientists from the Biotechnology Center of the TU Dresden (BIOTEC), the Max Planck Institute of molecular Cell Biology and Genetics (MPI-CBG), the Cluster of Excellence Physics of Life (PoL) at the TU Dresden, the Max Planck Institute for the Physics of Complex Systems (MPI-PKS), the Flatiron Institute, NY, and the University of California, Berkeley, have found evidence to answer the question of what triggers this cell fate decision between life and death in the germline.

Prior studies revealed the genetic basis and biochemical signals that drive physiological cell death, but the mechanisms that select and initiate apoptosis in individual germ cells remained unclear. As germ cells mature along the gonad of the nematode, they first collectively grow in size and in volume homogenously. In the study just published in Nature Physics, the scientists show that this homogenous growth suddenly shifts to a heterogenous growth where some cells become bigger and some cells become smaller.

TIL a preprint publication points to another commonality found in blue zones: their lack of birth records. Author Dr. Saul Justin Newman concludes, “the designated ‘blue zones’ of Sardinia, Okinawa, and Icaria corresponded to regions with low incomes, low literacy, high crime rate and short life expectancy relative to their national average. As such, relative poverty and short lifespan constitute unexpected predictors of centenarian and supercentenarian status, and support a primary role of fraud and error in generating remarkable human age records.”

Can the blue zone diet help with longevity? We investigate Dan Buettner’s claims about blue zones and the corresponding lifestyle.

Papers referenced in the video:

FGF21 and Chronic Kidney Disease: https://www.sciencedirect.com/science/article/pii/S002604952100038X

Continue reading “High FGF21, Low Insulin And Glucose: A Pro-Longevity Strategy?” »