PINK1: Mitochondrial quality control

PINK1 is the cell’s surveillance system for damaged mitochondria. An unusual kinase, it only stabilizes in the presence of a depolarized mitochondrion; once stabilized, it activates a mitophagy pathway that leads to clearance of the damaged organelle.

PINK1 activation has been shown to oppose the inflammation, mtDNA mutations, and metabolic/proteostatic failures that can lead to cell death in disease.

LEARN MORE: Mitokinin

AMBAR Therapeutic plasma exchange

AMBAR is an innovative clinical trial aimed at slowing down the progression of Alzheimer’s disease through periodic therapeutic plasma exchange.

AMBAR targets a multimodal approach to the management of the disease based on the hypothesis that most of the amyloid-beta protein is bound to albumin and circulates in plasma. Extracting this plasma may flush amyloid-beta peptide from the brain into the plasma, thus potentially limiting the disease’s impact on the patient’s cognitive functions. Additionally, albumin has binding capacity and antioxidant properties, and both albumin and immunoglobulin display immunomodulatory and anti-inflammatory properties.

Based on this hypothesis, the build-up of beta-amyloid could be reduced before it can cause neuronal damage, thus potentially limiting the impact of Alzheimer’s disease on cognition.



Mitophagy in cellular homeostasis

Pathogenic protein species implicated in neurodegenerative diseases (e.g., alpha synuclein, beta amyloid, tau, and TDP43) can associate with mitochondria and drive mitochondrial dysfunction.

Mitophagy, the process by which cells clear their damaged mitochondria, plays an important protective role in these circumstances: not only is the normal, healthy mitochondrial pool restored, but the proteotoxic species are cleared along with the bad mitochondria.

Mitokinin’s scientists have shown that by potentiating the PINK1 pathway in times of proteotoxic stress, neuron health can be restored and disease-driving pathologies reduced or eliminated.

LEARN MORE: Mitokinin

Fasting to delay aging

In this video I discuss different types of fasting diets (both periodic and intermittent) and the underlying molecular mechanisms and why they have potential to delay aging and aging-related diseases. In particular we will address the importance of refeeding, which is more intense in periodic fasting (and fast mimicking diets [FMD]) due to the more severe fasting length, and activation of stem cells for regeneration & rejuvenation of tissues. We will also discuss the pros and concerns for fasting and how fasting overlaps or doesn’t overlap with anti-aging supplements.

Epigenetic reprogramming

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

Scholar Rock

Targeting growth factors

Cells produce protein growth factors in the precursor, or latent, form. For the mature growth factor to carry out its function, it must be activated (through molecular events) and separated from the prodomain.

Scholar Rock monoclonal antibodies target the prodomain of the precursor, or latent form of growth factors, and block the cage’s lock to inhibit activation. Given the much greater structural differences of the prodomain, we leverage this variance to achieve extraordinary selectivity.

With greater selectivity, we aim to minimize toxicity that have challenged approaches that target the mature form of growth factors.

LEARN MORE: Scholar Rock

CohBar Mitochondrial-derived Peptides

CohBar is a clinical stage biotechnology company focused on the research and development of mitochondria based therapeutics. Mitochondria based therapeutics originate from the discovery by CohBar’s founders of a novel group of naturally occurring mitochondrial-derived peptides within the mitochondrial genome that regulate metabolism and cell death, and whose biological activity declines with age.

To date, the company has discovered more than 100 mitochondrial derived peptides and generated over 1,000 analogs. CohBar’s efforts focus on the development of these peptides into therapeutics that offer the potential to address a broad range of diseases.