Delaying and reversing the effects of aging have long been sought by researchers, so a long-standing dream has been to find anti-ageing drugs.
Heparin successfully caused full length tau amyloid aggregation in the presence of monomeric species as indicated by ThT fluorescence, as we tested whether doxycycline could prevent this process.
1. Antioxidant
Researchers have recently discovered that taking the antibiotic doxycycline dramatically extends mouse lives. This is because this particular antibiotic causes mitochondrial DNA depletion, stopping mitochondria from providing 90 percent of their energy needs – such as respiration, repair and growth processes – along with producing energy substrates such as Adenosine Triphosphate (ATP). Mitochondria are vital organelles which produce energy needed for respiration, repair and growth processes as well as producing energy substrates like Adenosine Triphosphate (ATP), making their function essential. Unfortunately mitochondrial dysfunction is linked to human diseases including cardiovascular disease, age related neurological disorders as well as diabetes.
Alcohol consumption is a risk factor for cardiovascular disease and hastens endothelial cell senescence, and we tested whether doxycycline could attenuate these effects by administering 400 mM ethanol alone or combined with 10 g/mL doxycycline for two days; then we utilized TeloTest Kit measurements of telomere length change; our results show that doxycycline significantly attenuated this acceleration of shortening using alcohol-accelerated methods in HUVECs treated this way; our results showed significant attenuation by this treatment of 400 mM ethanol-accelerated shortening in HUVECs by inhibiting molecular events associated with 400 mM ethanol-related molecular events associated with endothelial cell senescence; our results revealed significant attenuation by doxycycline from other treatment regimens of 400mM ethanol alone or combined with 10g/mL doxycycline significantly attenuated the effects of 400mM ethanol treatment by attenuating molecular events associated with molecular events associated with its acceleration of shortening through TeloT Test Kit quantification method of shortening by significantly attenuating its effects, using TeloT Test Kit analysis of shortening as well. The TeloTest kit data confirmed its significant attenuating its effectiveness at attenuated shortening.
This effect was amplified when combined with Azithromycin, an established inducer of autophagy. When taken together with its known brain bioavailability, safety, and antioxidant properties of Doxycycline, these findings show its suitability as a repurposed treatment option for tauopathy.
2. Anti-inflammatory
Ethanol accelerates human endothelial cell aging by shortening telomeres and inducing cell senescence [1-3]. Senescent cells release MMPs that play an essential role in vascular remodeling and age-related diseases [4, 5]. We conducted this study to investigate whether doxycycline protects against ethanol-induced vascular senescence through inhibiting MMP activity. HUVECs were treated with 10uM concentration doxycycline to inhibit their MMPs while MMP-1, MMP-2, MMP-3-4 MMP-5 and MMP-11 were significantly decreased; these results were observed by decreasing relative MMP mRNA expression of MMPs 1-5 11 but not MMP-13 MMP-8 or MMP-9 as well as decreasing SASP.
Doxycycline was shown to prevent activation of NFk-B and transcription of MCP-1, E-selectin, ICAM-1, and VCAM-1 genes; these results suggest that doxycycline effectively mitigated ethanol-induced inflammaging by directly restricting leukocyte migration, adhesion, and infiltration into vascular endothelium.
Doxycycline also reverses C. elegans’s accumulation of lipofuscin, an aging pigment. After 13 days of treatment with doxycycline, lipofuscin had decreased significantly and their ability to move their pharynx increased, suggesting improved pharyngeal muscle function from taking this medication.
Doxycycline also prevents early accumulations of synuclein that have been thought to contribute to neurodegeneration by redirecting its aggregation process toward nontoxic off-pathway oligomers, rather than toxic oligomers that accumulate quickly in early oligomer forms. Doxycycline’s broad spectrum bactericidal activities, brain bioavailability and safety make it an attractive candidate for treating tauopathies in humans. Further research must be completed in this regard before drawing any definitive conclusions from it. However, Doxycycline’s multifaceted effects could explain its inconclusive clinical trial results and serve as an alternative therapy for Alzheimer’s disease and related tauopathies. We hope that future research studies will reveal its anti-ageing mechanism.
5. Anti-aging
Anti-aging has long been the goal of scientists, who aim to extend life expectancy and extend healthspan (the number of healthy years). By delaying or stopping the aging process altogether, scientists hope they can reverse metabolic dysfunction that causes diseases as well as organ malfunction and function loss.
Scientists have researched various approaches to anti-aging, such as gene therapy, dietary supplements and therapeutic interventions. A significant area of research involves cellular reprogramming; studies on mice have demonstrated its ability to partially reverse age-related phenotypes. Over the last decade a team of scientists developed a system using OCT4 (O), SOX2 (S), and KLF4 (K) transcription factors known as Yamanaka factors for this process; these transcription factors can be either temporarily induced into somatic cells so as to transform them into pluripotent stem cells able to produce any cell type that will eventually make progress easier overall.
Reintroducing these cells back into the organism to restore homeostasis is possible; however, reprogramming is an expensive and time-consuming process which often requires special cell culture conditions and is still unknown whether this treatment works effectively on humans.
Researchers have explored two antibiotics — doxycycline and azithromycin — which target various components of bacteria or mitochondria’s protein-making machinery, to counter the limitations of their approach. When tested at various concentrations in C. elegans, both drugs significantly extended median lifespan while decreasing visible signs of aging.
The researchers discovered that doxycycline and azithromycin had anti-synuclein effects by blocking production of new proteins encoded by mitochondrial DNA, stimulating autophagy to selectively eliminate defective mitochondria, binding tubulin and blocking its acetylation; adding Vitamin C further enhanced this combination’s anti-ageing benefits, maintaining pharyngeal muscle contractions and decreasing lipofuscin accumulation by 90%.
