Screening And Anti-aging Activity Study Of The Human Telomerase Reverse Transcriptase(hTERT)Expression Promoting Agents

Aging is one of the major scientific fields of human health problems,problems caused by the aging of tissues and organs of the body has posed a serious challenge.Studies have shown that telomere length plays an important role in cell senescence,holistic physiological and pathological processes of aging and age-related diseases,and telomere length has even been used as a marker of biological aging.Telomerase is a ribose nucleoprotein complexes,which is responsible for increasing cell telomeres,and its activity is closely related to the expression of human telomerase reverse transcriptase(hTERT).Expression of hTERT promotes telomerase and anti-aging or immortalized capabilities.Therefore,the hTERT expression promoting agents are expected to become the new anti-aging strategy.In this paper,luciferase reporter system and constructed the hTERT expressing compound screening system were used to screen 156 kinds of small molecule compounds from the Tianjin University of Science and synthetic drug screening laboratory.HKL2-3-35,was obtained as a(hTERT)expression promoting agent.HeLa cells were treated with 4?M and 8?M of HKL2-3-35 and showed that HKL2-3-35 promotes the extension of telomeres,cell proliferation and migration.HKL2-3-35 accelerates the cell transition from G1 to S phase.Treatment of human embryonic fibroblasts with 0.25?M and 0.5?M HKL2-3-35 indicated that HKL2-3-35 has obvious anti-aging effects.In addition,a series of environmental factors was screened and discovered that acid,caffeine and ethyl acetate promote the expression of hTERT,and they have the similar effect with HKL2-3-35,but with higher specificity.Further study found that HeLa cells treated with acetic acid and caffeine treatment decrease the p21 and p53 mRNA level by 58.6%and 31.4%and caffeine treatment decrease the p21 and p53 mRNA level by 11.6%and 31.3%,indicating that the hTERT expression promoting agents accelerate the cell cycle,enhance cell viability,and slow cellular aging.In summary,four hTERT expression promoting agents,including HKL2-3-3,acetic acid,caffeine and ethyl acetate were screened.This study provides more evendence for the roles of telomerase in regulating ageing and provides a new strategy for the treatment of aging-related diseases.