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Longevity and rejuvenation effects of cell reprogramming are decoupled from loss of somatic identity

Partial somatic cell reprogramming has been touted as a promising rejuvenation strategy. However, its association with mechanisms of aging and longevity at the molecular level remains unclear. We identified a robust transcriptomic signature of reprogramming in mouse and human cells that revealed co-regulation of genes associated with reprogramming and response to lifespan-extending interventions, including those related to DNA repair and inflammation. We found that age-related gene expression changes were reversed during reprogramming, as confirmed by transcriptomic aging clocks. The longevity and rejuvenation effects induced by reprogramming in the transcriptome were mainly independent of pluripotency gain. Decoupling of these processes allowed predicting interventions mimicking reprogramming-induced rejuvenation (RIR) without affecting somatic cell identity, including an anti-inflammatory compound osthol, ATG5 overexpression, and C6ORF223 knockout. Overall, we revealed specific molecular mechanisms associated with RIR at the gene expression level and developed tools for discovering interventions that support the rejuvenation effect of reprogramming without posing the risk of neoplasia.

Aging is associated with the buildup of molecular damage and a gradual loss of function, culminating in chronic age-related diseases and ultimately death (1). Searching for safe and efficient interventions that can slow down or partially reverse the aging process is a major challenge in the aging field (2 6). In this regard, reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) has been proposed as a candidate longevity intervention due to its potential to rejuvenate cells in a targeted way (7, 8).

Pluripotency can be achieved in vitro by the ectopic expression of four transcription factors: OCT4, SOX2, KLF4, and MYC, known as OSKM or Yamanaka factors (YFs). It was demonstrated that OSKM support the generation of murine iPSCs using retroviral transduction as a delivery system and mouse embryonic fibroblasts (MEF) as the initial cell culture. Although this original experiment was inefficient in terms of the percentage of cells that terminally achieved the pluripotent state (0.1%), more advanced in vitro approaches resulted in a greatly improved efficiency, e.g. by down-regulation of methyl CpG-binding domain 3 (MBD3) levels (10). In parallel, other approaches have been developed to induce pluripotency. In particular, the expression of seven other transcription factors (7F: Jdp2-Jhdm1b-Mkk6-Glis1-Nanog-Essrb-Sall4) resulted in high efficiency of reprogramming (11).

New FDA-Approved Eyedrops Could Improve Close-Up Vision

Dec. 14, 2021 — A new FDA-approved eyedrop medicine could replace reading glasses for millions of Americans who have age-related blurry vision.

The product, called Vuity, was approved by the FDA in October and went on the market last week. The new medicine begins working in about 15 minutes and provides sharper vision for 6 to 10 hours.

Vuity is the first FDA-approved eyedrop to treat the condition known as presbyopia, which tends to affect people ages 40 and older. The prescription drug uses the eye’s natural ability to reduce its pupil size.

Transhumanism and Human Genetic Engineering — ROBERT SEPEHR

Transhumanism advocates the use of current and emerging technologies such as genetic engineering, artificial intelligence, and nanotechnology, to augment human capabilities, enhance longevity, and improve cognition. The term “designer baby” refers to a child who would develop from an embryo or sperm or egg that had been genetically altered. Is there a covert political agenda behind this allegedly altruistic scientific movement?

Robert Sepehr is an anthropologist and author.
(books also available through other book outlets)
http://amazon.com/Robert-Sepehr/e/B00XTAB1YC/

Robert Sepehr Links.
https://linktr.ee/RobertSepehr.

Support Robert Sepehr on Patreon:
https://www.patreon.com/AtlanteanGardens

Peter Diamandis: In 10 Years Tech Will Reset Your Age

Slowing speed of aging will increase life expectancy.


Peter Diamandis, the founder of the Singularity University and the X Prize Foundation has a goal for the next decade: to add 20 or 30 healthy years to people’s life. Or, in other words, making 100 years old the new 60s. He presents his vision during “Priorities”, a summit that took place on September 2022 in New York and organized by the FII Institute. Here are the highlights.

#Reverseaging

Cellular ‘glue’ can regenerate tissues, heal wounds and regrow nerves

Researchers at UC San Francisco (UCSF) have engineered molecules that act like “cellular glue,” allowing them to direct in precise fashion how cells bond with each other. This discovery represents a major step toward building tissues and organs, a long-sought goal of regenerative medicine [1].

Longevity. Technology: Adhesive molecules are found naturally throughout the body, holding its tens of trillions of cells together in highly-organised patterns. They form structures, create neuronal circuits and guide immune cells to their targets. Adhesion also facilitates communication between cells to keep the body functioning as a self-regulating whole.

Now a new study, published in Nature, details how the researchers engineered cells containing customised adhesion molecules that bound with specific partner cells in predictable ways to form complex multicellular ensembles.

Raising Awareness that Aging is a Problem Worth Solving

Awareness about aging and early symptom of disease can extend life to much more year.


There has been plenty going on here at Lifespan.io, so we thought it was time to give you a little update on what’s been happening.

Longevity Summit

The Longevity Summit 2022 is happening on December 6–7 at the Buck Institute for Research on Aging, and Lifespan.io is an official media partner! As a special bonus to our readers, you can purchase tickets here with a 15% discount using the code LifespanIO.

Our Executive Director Stephanie Dainow will be hosting a discussion panel during the event. If you are at the conference, please do come and say hello, as we are always interested in meeting people in the industry and exploring ways to collaborate.

Robust Mouse Rejuvenation

LEV Foundation’s flagship research program is a sequence of large mouse lifespan studies, each involving the administration of (various subsets of) at least four interventions that have, individually, shown promise in others’ hands in extending mean and maximum mouse lifespan and healthspan.

We focus on interventions that have shown efficacy when begun only after the mice have reached half their typical life expectancy, and mostly on those that specifically repair some category of accumulating, eventually pathogenic, molecular or cellular damage. The first study in this program is starting in January 2023.

Paul Thagard — Substrate-Independent Minds

Is digital immortality possible by uploading your mind? Dr. Paul Thagard discusses Neuralink, artificial intelligence, mind uploading, simulation theory, and the challenges involved with whole brain emulation.

Dr. Paul Thagard is a philosopher, cognitive scientist, and author of many interdisciplinary books. He currently teaches as a Distinguished Professor Emeritus of Philosophy at the University of Waterloo, where he founded and directed the Cognitive Science Program.

Dr. Thagard is a graduate of the Universities of Saskatchewan, Cambridge, Toronto (with a PhD in philosophy) and Michigan (with an MS in computer science). He is a Fellow of the Royal Society of Canada, the Cognitive Science Society, and the Association for Psychological Science. The Canada Council awarded him a Molson Prize in 2007 and a Killam Prize in 2013.

LINKS & RESOURCES:

Dr. Paul Thagard’s Website:

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Balance: How It Works and What It Means.

Size Matters in Cellular Aging

In a new review article published in Frontiers in Cell and Developmental Biology, researchers have suggested adding cellular enlargement to the hallmarks of aging [1].

Different cell types are known to have different shapes and sizes, which are dictated by their functions. In humans, sperm cells (male gametes) and ova (female gametes) have the smallest and largest diameters, respectively. On the other hand, some neurons are the longest cells: their axons can be over a meter long.

Nevertheless, within a specific cell type, the size variation is negligible. It has been long observed that healthy cells tend to maintain their size and that size changes are characteristic of pathological conditions. Cancer cells are often smaller than normal cells, while senescence leads to cellular enlargement [2].

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