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Global Translational Medicine Metabolic dysfunction in vascular senescence

4.2.1. Rapamycin age. Therefore, long-term regular exercise serves as an

The mammalian target of rapamycin protein (mTOR) effective intervention for enhancing SIRT3 expression
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is a vital regulatory factor involved in cellular growth and mitigating age-related diseases. Regular physical
and proliferation. By inhibiting mTORC1, rapamycin activity and exercise play a pivotal role in the primary and
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secondary prevention of cardiovascular diseases.
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reduces cellular growth, proliferation, and metabolic rate,
while enhancing autophagy. These effects highlight the 4.3.2. Dietary regulation
potential of rapamycin and its analogs, such as everolimus
and sirolimus, in the research and treatment of cancer, Reducing the content of branched-chain amino acids
senescence, and various metabolic disorders. Rapamycin in the diet can simulate starvation and extend the
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can reportedly improve health conditions associated with lifespan of fruit flies. In addition, mTORC1 modulates
senescence, extend the lifespan of model organisms, and growth factor signaling by regulating cell anabolism
reduce the incidence of age-related diseases. mTOR and nutrient sensing through the RagGTPase signaling
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inhibition delays stem cell senescence and prolongs the pathway. Reduced intracellular nutrition levels inhibit
lifespan of eukaryotes. Further, rapamycin can delay the the RagGTPase signaling pathway, which suppresses the
senescence of dental pulp stem cells by inhibiting protein mTORC1 signaling pathway. Therefore, manipulation of
homeostasis and impaired intercellular signal transduction the diet composition, such as caloric restriction, fasting, or
and regulating mitochondrial dysfunction. The results of dietary protein content increase, can inhibit the mTORC1
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clinical trials conducted on the skin have also shown that signaling pathway and delay senescence progression.
rapamycin administration reduces p16 INK4A expression, 5. Conclusion
which is consistent with cellular senescence and suggests
that rapamycin therapy is a potential antisenescence Senescence is a complex physiological process that
treatment. 69 intensifies with advancing age and leads to structural and
functional changes in tissues and organs. Cardiovascular
4.2.2. Melatonin diseases are the leading cause of mortality worldwide and
MSCs are a commonly used source for various stem are attracting broad research attention. In recent years,
cell-based therapies. Melatonin is a highly effective senescence has been identified as a significant risk factor
antioxidant predominantly used for treating insomnia, for cardiovascular diseases, highlighting the importance of
jet lag, depression, anxiety, pre-menstrual syndrome, and understanding its impact on the vascular system. Notably,
menopausal symptoms and supporting immune system investigations into cellular senescence mechanisms
functions. Although initially recognized for its role in have focused on endothelial cells, smooth muscle cells,
regulating sleep and circadian rhythms, melatonin possesses macrophages, and stem cells because of their direct
substantial antioxidant properties. It effectively neutralizes influence on vascular function and contribution to the
free radicals and mitigates oxidative stress through development and progression of cardiovascular diseases.
several mechanisms – direct free-radical scavenging, Senescence involves multifaceted mechanisms, such as
enhancement of endogenous antioxidant enzyme activity, stem cell senescence, cellular metabolic dysregulation,
and improvement of the cellular antioxidant defense mitophagy, and ferroptosis.
system. These actions position melatonin as a remarkably This review aimed to comprehensively summarize
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effective agent in combating senescence, inflammation, and the mechanisms underlying senescence, while proposing
cellular damage, exceeding initial expectations. Research potential strategies to counteract them, with the goal of
demonstrates that melatonin enhances the expression offering new therapeutic insights into diseases related
of heat shock protein family A (Hsp70) member 1-like, to vascular senescence. Strategies targeting stem cell
which subsequently promotes mitophagy and facilitates senescence may involve interventions in the stem cell
the removal of damaged mitochondria. In addition, microenvironment, aimed at delaying senescence. Cellular
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melatonin exhibits antioxidant properties that alleviate metabolic dysregulation might be achieved through
age-related oxidative stress, protecting the functionality of optimizing metabolic pathways and enhancing metabolic
MSCs and ultimately delaying MSC senescence. 71 regulation. Mitochondrial function protection and
optimization might be achieved by applying antioxidants,
4.3. Other interventions whereas intervention in ferroptosis requires the regulation

4.3.1. Exercise of iron metabolism and related pathways.
Chronic endurance exercise training (≥8 weeks) can When cardiovascular diseases coexist with other
improve age-induced SIRT3 inhibition regardless of systemic conditions, such as diabetes, metabolic syndrome,

Volume 3 Issue 4 (2024) 9 doi: 10.36922/gtm.4619