Lowering the epigenetic age
Several studies have shown that OSKM induction (where O stands for Oct4) lowers epigenetic age gradually.
Having discovered this gradual property of epigenetic reprogramming, we can now be cautiously optimistic that we will manage to find a safe therapeutic window (such as marked by a yellow box in the graph) – that is, a period of safe epigenetic rollback when the methylation profile of a cell has been returned to a younger state but the cell has not lost its functional characteristics (for example, a skin cell would remain a skin cell rather than getting dedifferentiated into a pluripotent cell).
READ MORE: Youthereum Genetics
Human tissue 3D printing
Explore the science of bioprinting, a type of 3D printing that uses bioink, a printable material that contains living cells.
At Alkahest, we are decoding the plasma proteome to discover key proteins that increase or decrease with age, which we call chronokines. We then interrogate the chronokines to find those which act as key checkpoint nodes of biological aging, whether driving beneficial pathways like homeostasis, tissue repair, neural functioning and stem cell regeneration, or those detrimental pathways that cause tissue damage, inflammation, and neurodegeneration.
From those with the most impact on biological function, we create transformative therapies that halt or reverse the harmful effects of aging in critical diseases and alleviate their devastating consequences afflicting patients around the world. Our simple, elegant approach capitalizes on the body’s natural regulatory and communication mechanism: the plasma proteome.
The potential influence of chronokines in diseases of aging has inspired our therapeutic approach, which has so far delivered three candidates into Phase II clinical trials. In preclinical studies, Alkahest scientists demonstrated that our therapeutic targets activate molecular signaling pathways in older animals that include increased tissue regeneration, reduced age-related cognitive impairment, reduced neuroimmune activation, increased memory function.
Our current clinical trials are testing our therapeutic approaches for a range of age-related medical conditions, including Alzheimer’s disease, Parkinson’s disease, Age-Related Macular Degeneration, post-surgical recovery and others.
NAD+ is a redox-active metabolite, the depletion of which has been proposed to promote aging and degenerative diseases in rodents. However, whether NAD+ depletion occurs in patients with degenerative disorders and whether NAD+ repletion improves their symptoms has remained open.
Here, we report systemic NAD+ deficiency in adult-onset mitochondrial myopathy patients. We administered an increasing dose of NAD+-booster niacin, a vitamin B3 form (to 750-1,000 mg/day; clinicaltrials.gov NCT03973203) for patients and their matched controls for 10 or 4 months, respectively.
Blood NAD+ increased in all subjects, up to 8-fold, and muscle NAD+ of patients reached the level of their controls. Some patients showed anemia tendency, while muscle strength and mitochondrial biogenesis increased in all subjects. In patients, muscle metabolome shifted toward controls and liver fat decreased even 50%.
Our evidence indicates that blood analysis is useful in identifying NAD+ deficiency and points niacin to be an efficient NAD+ booster for treating mitochondrial myopathy.
SOURCE: Cell Metabolism
EDITOR’S NOTE: Increased blood levels of NAD+ were achieved here with a readily available supplement, niacin (vitamin B3).