What is Proxofim Peptide (FOXO4-DRI)?

by | Apr 11, 2022 | Research

Proxofim is a senolytic antagonistic peptide fragment. It mainly aims at blocking the interaction between forkhead box 04 and the enzyme p53.
Aging or senescence is a normal physiological process whereby the body cells stop dividing and undergo apoptotic death.

Even though aging is a normal biological process, it proves harmful to the body. It plays an etiological or causative role in several pathologies. Senescence, therefore, contributes to the overall decline in the health of the body.

Reversing the physiological process of aging and preventing its detrimental effects on bodily health has long been a center of research and interest for scientists.

Proxofim (FOXO4-DRI) is the newest development due to these studies.

How Does Proxofim Work?

Senescence is a cellular state where it becomes arrested at a stable stage without undergoing any more replication. These senescent cells become resistant to all growth signals directed at them. Such a type of response results in DNA damage in the cell.

Aging is a progressive decline in the health of the body, and senescence is a part of it. Senescence mainly differentiates from aging in its timing, i.e., it can occur during the lifespan.

A senescent cell has typical characteristics which make it easy to identify one. A senescent cell has protective and harmful properties, part of a physiological process.

Researchers use many approaches to reverse aging. The most useful has been the selective elimination of senescent cells.

This stage is where Proxofim comes into action. It is designed in such a way that it tries to disrupt the interaction between FOXO4 and p53. Doing so directs the p53, which has been excluded from the nucleus, towards the mitochondria. p53, being the critical controller of cellular division and death, causes the stimulation of the apoptotic pathway in the targeted senescent cells.

In studies conducted on mice, there has been significant evidence that Proxofim administration showed vital improvement in the previously declining health.

Proxofim experimental benefits

Although still in the clinical trial phase, the use of Proxofim has shown promising results in the following areas.

Insulin Signalling
Proxofim has long been considered a protein with significant downstream regulatory effects on insulin and insulin-like growth factors. Animal research has shown that Proxofim is involved in the acute inhibitory effects of insulin on processes related to cellular metabolism, differentiation, oxidative stress, etc.

FOXO mutations have been well-documented in various pathological complications of insulin signaling and metabolic disorders. Hyperglycemia and hyperlipidemia are two complications that result from impaired FOXO signaling in diabetics.

These two conditions have high morbidity and mortality. It calls for the need to regulate FOXO signaling in diabetics. Even though there is a lack of sufficient studies on how it manages to do this, Proxofim significantly brings down the fasting blood glucose concentration in people with diabetes.

Neurodegenerative Diseases
Neurodegenerative conditions like Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, etc., are some of the unfortunate age-related conditions that are the inevitable consequences of the aging process. Some of these diseases lead to changes in proteasome activity in the CNS.

Proxofim modifications have also been noted in these conditions. It has led researchers to believe that it might have some role to play here. Although still in developmental stages, the use of Proxofim has been positively implicated in reversing or facilitating, at the very least, these neurodegenerative conditions.

Heart Diseases
Heart diseases are often age-related complications. Cardiovascular diseases have been linked with an upset in the balance of proteasome activity in the heart. When proteasome activity declines, the risk for CVS disorder starts rising. This rise is because the primary function of proteasomes is to remove oxidized, otherwise deemed as “dysfunctional or damaged” proteins from the heart, which can be a potential source of cardiac damage.

In studies conducted on mice, it has been seen that a decline in proteasome activity is also related to increases in age, which further solidifies the argument that heart issues are common with advancing age.
Proxofim protein acts as a mediator for proteasome activity as well as autophagy. It may therefore be helpful to investigate Proxofim’s role in maintaining the normal functioning of the heart. It can lead to minimizing all the age-related changes taking place.

Proxofim is a potent anti-aging molecule. It acts on a cellular level to reverse the molecular processes related to aging. Therefore, it has a significant potential for use in several age-related conditions.

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