THE 'CEUTICALS' |
TA-65md repairs the ravages of chronic infections
lifetime. Over 70% of older people suffer from immunodeficiency and are considered immuno- compromised. Immunodeficiencies result from a variety of immunosuppressive agents, such as ageing, chemotherapy, radiation, HIV, cytomegalovirus (CMV), Epstein–Barr virus (EBV), and many types of cancers (including leukaemia, lymphoma, and multiple myeloma).
H Immunodeficiencies are
characterised by a dramatic decline in immune function and in particular, this occurs with chronic infections that impair the immune system’s ability to ward off disease. It is therefore important that the immune system remains robust and capable of combating both new and repeat pathogenic offenders. Some of the most important changes that occur in the immune system involve lymphocytes, and in particular, the CD8 (or cytotoxic) T-cells. These lymphocytes are predominantly responsible for recognising viral antigens and undergoing massive cell division in order to create a population substantial enough to eliminate infected or abnormal cells. They also secrete antiviral cytokines that can suppress viral replication. However, with prolonged stress of the immune system, extensive CD8 cell turnover and proliferation occurs, eventually leading to replicative senescence. This is the case during chronic viral infections, where it has been shown that there is a high proportion of senescent
umans are exposed to an increasing number of pa thoge ns throughout their
CD8 cells compared with the naïve population (Goronzy, 2001). Replicative senescence in CD8
T-cells is driven in large part by the extensive cell proliferation required to control viral infections. The process itself has been well characterised and is known to be one of the major mechanisms underlying the shaping of the T-cell population in the human immune system. The CD8 T-cell replicative senescence cascade is modulated by a number of factors, involving roles by telomeres, telomerase, and the CD28 co-stimulatory receptor. Understanding this process sheds light on immune function during chronic infection
Senescent CD8 cells can be a
problem for a number of reasons. Their mere presence can have a detrimental effect on the immune system because they impact the activity of surrounding cells.
Since
the senescent cells are no longer proliferative, but are still metabolically active, they influence their micro-environment. It has been suggested that the presence of senescent CD8s influence the naïve T-cell pool (Boucher, et al., 1998; Campisi, 1997). Furthermore, after the senescence cascade has been initiated, CD8 cells begin to increase secretion of pro-inflammatory cytokines and decrease the secretion of antiviral factors. They may also have a reduced ability to respond to stress and repair damaged DNA (Effros, 2011).
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TA-65: rejuvenation of the immune system TA-65, a small-molecule single-entity naturally-derived compound, activates telomerase in human cells and in animal models (Fauce, et al., 2008; Bernardes de Jesus, et al., 2011; Harley, et al., 2011). In an observational human study, TA-65 decreased the abundance of short telomeres and had positive effects
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on the immune system (Harley, et al., 2011). More specifically, the abundance of senescent immune cells (CD8+/CD28-) was significantly reduced, especially in CMV+ subjects. There was also a decrease in the percent and number of natural killer (NK) cells. This evidence suggests a significant role for TA-65 in immune system remodelling. Biomarker analyses of human subjects also revealed significant improvements in markers related to metabolism, cardiovascular health, and bone mineral density. The positive structure/function
effects that were observed in multiple tissue systems were also demonstrated in a vehicle-controlled animal study
"Some of the most important changes
that occur in the immune system
involve lymphocytes, and in particular, the CD8 (or cytotoxic) T-cells.
with TA-65 (Bernardes de Jesus, et al., 2011). A blinded study of mature mice demonstrated that TA- 65 administration led to a significant rescue of short telomeres, and an improvement in glucose tolerance scores, as well as an increase in both subcutaneous and epidermal thickness. In vitro analysis of TA-65-treated mouse keratinocytes also showed increased proliferation and mobilisation potential (Bernardes de Jesus, et al., 2011) In previous studies, it has been
shown that short-term exposure of a small molecule telomerase activator similar to TA-65 led to a significant enhancement of telomerase activity in T-cells from both healthy and HIV-infected individuals. The observed increase
in telomerase activity was of greater magnitude in cells from patients with HIV than in cells from healthy individuals, supporting the notion that healthy individuals have more substantial endogenous telomerase activity than patients fighting chronic infection. For HIV-specific CD8 T lymphocytes, the increased telomerase activity was accompanied by increased proliferation, and importantly, significant enhancement of a range of anti-viral functions (Fauce, et al., 2008). This suggests that a small-molecule telomerase activator is capable of extending the lifespan of cells by delaying senescence and up-regulating telomerase so that the shortest telomeres can be extended. Therefore, the ability to enhance
telomerase activity and antiviral functions of CD8+ T lymphocytes suggests that TA-65 could be useful in treating immunodeficiency conditions, as well as increased susceptibility to other viral infections associated with chronic infections (Targonski, Jacobson, & Poland, 2007).
TA-65: a solution for immunodeficiency TA-65 provides a naturally-derived solution for rejuvenating an immune system that has been impaired. TA-65 is unique in that it can repair critically short telomeres and extend the functional life-span of pre-senescent cells. These results cannot be obtained through a normal diet, as it takes high concentrations of this molecule to achieve telomere lengthening, which is the mechanism for cellular rescue and eventual rejuvenation. By repairing the immune system at the fundamental cellular level, TA- 65 may act as a useful complement to existing drug regimens for patients with chronic immune infections or immunodeficiency.
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