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Dr Brian Kennedy on Rejuvant, human longevity trials, aging optimally and why individual response to intervention is key.

Alpha-ketoglutarate (AKG) is used by cells during growth and in healing from injuries; studies have shown it may be effective in treating osteoporosis, preventing a decline in protein synthesis, reducing frailty and, in some mammalian studies; even extending lifespan. has gone one step further, adding calcium to produce LifeAKG™, a patent-pending, highly bioavailable and ultra pure CaAKG supplement, backed by extensive research and double-blind placebo-controlled clinical trials.

Brian Kennedy PhD, who was the Buck Institute’s second CEO, serves as Rejuvant’s Scientific Advisor; he is also a member of the Board. Currently, Dr Kennedy is Professor and Director of the Center for Healthy Aging at the National University of Singapore, and with a plethora of widely-cited papers on aging and longevity under his belt, he is regarded as an expert in the science of gerontology.

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Adult bone marrow (BM) houses a tiny pool of hematopoietic stem cells (HSCs) that have the ability to maintain not only themselves but also all the rest of highly turning over blood lineages throughout the mammalian life (1, 2). Hence, the ability to sustain HSC in tissue culture would allow serial introduction of gain or loss of function mutations efficiently in hematopoietic system. However, our failure to expand HSC in culture has hampered the use of this approach. In fact, BM suspension cultures lose rapidly their HSC content despite vigorous growth of progenitors and more differentiated cells at least for 3 weeks even in optimal cytokine milieu (3, 4). Therefore, the phenomenon of stem cell exhaustion or senescence may set the limits that make it impossible even in principle to expand HSC in culture for longer periods (5–7).

Mouse HSC do expand in vivo (8, 9), at least up to 8000-fold, as shown by Iscove and Nawa (9) through serial transplantation experiments that assessed carefully the input and output contents of HSC in each transfer generation. Recently also in vitro approaches have been improved and refined culture conditions with new growth factors can now support up to 30-fold expansion of mouse HSC ex vivo (10). However, since it is not clear to what extent external culture conditions can be improved, alternative but not mutually exclusive efforts to change the intrinsic properties of HSC have been taken. Seminal experiments in this respect by Humphries, Savageau and their colleagues have shown that ectopic expression of HOXB4 transcription factor in BM cells support the survival and expansion of HSC in vivo and importantly also in vitro (11–13). By rigorously monitoring the HSC content in their cultures of HOXB4-transduced BM cells, they found that HSC could be expanded up to 41-fold in the 2-week liquid cultures (13). HOXB4 belongs to a large family of HOX transcription factors that are crucial for the basic developmental processes in addition to their role in maintenance of different stem cell compartments.

Capitalizing on the findings of Humphries, Savageau and their colleagues, we have established long-term murine BM cultures of HOXB4-transduced cells (HOX cells) and monitored their stem cell content to find out how extensively genetically modified HSC and their multipotent primitive progenitors (MPPs) can be expanded in culture for experimental purposes. In addition and for comparison, we established BM cultures transduced with constructs encoding for Nucleoporin 98 (NUP)–HOXB4 (NUP cells) fusion protein again following the lead of Humphries et al. (14) who showed that ectopic expression of similar fusions promoted in vivo even more robust expansion and survival of HSC.

A study on naked mole rats could help scientists prevent and better treat human illnesses.

According to new research conducted by University of Cambridge scientists, naked mole rats age healthily, very rarely get cancer, and are numb to acid.

The team hopes to utilize these insights to find better treatment methods for human illnesses and inflammatory conditions such as arthritis, according to an institutional press release.

With billions of dollars flooding into longevity, what role will epigenetic clocks play in measuring and intervening in aging?

When Horvath first described epigenetic clocks, scientists began to speculate that altering them could reverse aging. After all, if certain patterns of DNA methylation at certain sites in cells in certain tissues of your body are hallmarks of aging, could shifting them somehow reverse aging?

The biotech platform that is leveraging one of the cornerstones of evolution – mitochondria.

Mitochondria play a crucial role in the aging process, activating factors and metabolic pathways involved in longevity. Their dysfunction impacts on both lifespan and healthspan, and whilst they have been identified as disease targets for some time, mitochondria have proven difficult to treat.

The founders of cellvie wondered if it were possible, as they put it, to leverage one of the cornerstones of evolution – to replace and augment damaged mitochondria. And so, the concept of Therapeutic Mitochondria Transplantation was born. TMT holds the potential of sustainably affecting mitochondria function, and reinvigorating or amplifying the cellular energy metabolism – and having raised $5 million in Kizoo-led seed funding, cellvie is on the way to turning that possibility into a reality.

Dr Alex Schueller, Cellvie’s CEO, will be speaking at Berlin’s Rejuvenation Startup Summit (14−15 October 2022), as part of an all-star line-up that includes Michael Greve, Eric Verdin, Brian Kennedy, Michael Sidler, Christian Angermayer and our own Phil Newman. Hosted by the Forever Healthy Foundation, this vibrant networking event aims to accelerate the development of the rejuvenation biotech industry.

With the aid of physics and a minuscule magnet, researchers have discovered a new structure of telomeric DNA. Telomeres are sometimes seen as the key to living longer. They protect genes from damage but get a bit shorter each time a cell divides. If they become too short, the cell dies. The new discovery will help us understand aging and disease.

Physics is not the first scientific discipline that springs to mind at the mention of DNA. But John van Noort from the Leiden Institute of Physics (LION) is one of the scientists who found the new DNA structure. A biophysicist, he uses methods from physics for biological experiments. This also caught the attention of biologists from Nanyan Technological University in Singapore. They asked him to help study the DNA structure of . They have published the results in Nature.

Biotech start-up Pretzel Therapeutics launched Monday with $72.5 million in Series A financing to develop novel, mitochondria-based therapies for rare genetic disorders and diseases of aging.

Pretzel plans to target mitochondrial diseases, a highly heterogenous group of conditions caused by DNA mutations in the mitochondria or the nucleus. These disorders are very rare, afflicting around one in 5,000 people.

Pretzel CEO Jay Parrish told BioSpace the fundingshould enable us to get close to the clinic if not into the clinic with one or more programs.”