Discovery of potent telomerase activators: Unfolding new therapeutic and anti-aging perspectives

Abstract

Telomere length, a marker of cellular aging, decreases with age and it has been associated with aging-related diseases. environmental factors, including diet and lifestyle factors, affect the rate of telomere shortening which can be reversed by telomerase. Telomerase activation by natural molecules has been suggested to be an anti-aging modulator that can play a role in the treatment of aging-related diseases. This study aimed to investigate the effect of natural compounds on telomerase activity in human peripheral blood mononuclear cells (PBMcs). The tested compounds included Centella asiatica extract formulation (08aGTlF), astragalus extract formulation (nutrient 4), Ta-65 (containing Astragalus membranaceus extract), oleanolic acid (oa), maslinic acid (Ma), and 3 multi-nutrient formulas (nutrients 1, 2 and 3) at various concentrations. The mean absorbance values of telomerase activity measured following treatment with some of the above-mentioned formulations were statistically significantly higher compared to those of the untreated cells. in particular, in order of importance with respect to telomerase activation from highest to lowest, 08aGTlF, oa, nutrient 4, Ta-65, Ma, nutrient 3 and nutrient 2, triggered statistically significant increase in telomerase activity compared to the untreated cells. 08aGTlF reached the highest levels of telomerase activity reported to date, at least to our knowledge, increasing telomerase activity by 8.8 folds compared to untreated cells, while nutrient 4 and oa were also potent activators (4.3-fold and 5.9-fold increase, respectively). on the whole, this study indicates that the synergistic effect of nutrients and natural compounds can activate telomerase and produce more potent formulations. Human clinical studies using these formulations are required to evaluate their mode of action. This would reveal the health benefits of telomerase activation through natural molecules and would shed new light onto the treatment of aging-related diseases.

Telomere length and telomerase activity in osteoporosis and osteoarthritis (Review)

“…In particular, stem cell dysfunction caused by telomere shortening may be one of the mechanisms responsible for aging in both humans and mice (9). Of note, a recent study revealed that the administration of nutraceutical supplements to healthy individuals was implicated in TL maintenance (28).…”

“…In agreement with this, de Jesus et al previously demonstrated that the TA-65 component from Astragalus membranaceus root induced the elongation of short telomeres and the neutralization of associated DNA damage, in a telomerase-dependent manner (33). In addition to these studies, it has recently been demonstrated that specific natural compounds can significantly activate telomerase in human peripheral blood mononuclear cells in vitro (28).…”

Dermatologic Toxicities and Biological Activities of Chromium

“…Chromium as dietary supplement (50-200 μg) has been used in preventing skin aging by controlling and regulating blood sugar and lipid levels [17]. Either in topical or systemic applications, chromium is usually combined with different vitamins and minerals to obtain optimum results based on certain parameters such as improving insulin function using chromium picolinate [149], promoting mitochondrial biogenesis and lipid metabolism using oligomannuronate-chromium(III) complexes [150], replacing or removing excess iron production using chromium(III) chloride or chromium picolinate [151,152], and activating telomerase [153].…”

An Appraisal on the Value of Using Nutraceutical Based Senolytics and Senostatics in Aging

“…They are also being investigated in telomere biology. Telomerase is capable of reversing telomere erosion and has been targeted in peripheral blood mononuclear cells by plant derived telomerase activators (Tsoukalas et al, 2019). TA-65, a derivative of Astragalus membranaceus, has been shown to elongate telomerase in a telomere deficient mouse model (de Jesus et al, 2011).…”