A Targeted Approach
Aging is considered to be one of the most complicated and heterogeneous phenomena and is the main risk factor for most chronic diseases, disabilities, and declining health. Aging cells cease to divide and drive the progression of illness through various pathways. Over the years, a number of anti-aging medicines of natural and synthetic origin have been introduced. Indeed, some studies have identified senescent cells as potential therapeutic targets in the treatment of aging and age-related diseases..
Several reports have highlighted that mitochondria are a key factor in the progression of aging and neurodegenerative illnesses. This is due to their production of extra amounts of reactive oxygen species, which leads into progressive caspase-dependent apoptosis and cell death. Therefore, strategies to prevent/reduce oxidative stress-mediated aging, whether environmental, nutritional and pharmacological, need to be taken into account. Presently, Drosophila melanogaster and Caenorhabditis elegans, which focus on the evolutionary and genetic foundations of aging, have helped to establish the screening of several synthetic and natural compounds with large cohorts in a quick manner. However, there is yet to be any efficient experimental evidence to prove the exact role of senescent cells in age-related dysfunction and further studies are required to better understand these processes.
A new breakthrough in anti-aging research could lead to gene and stem cell therapies that turn back the hands of time.The search for the Fountain of Youth never gets old. Throughout history, humans have sought in vain to stop the clock on aging – or at least the outward signs of it – with make-up, plastic surgery, and dubious patent medicines. Now, however, a promising new twist in the fight against old age could propel the field of aging research beyond its snake-oil image. Recent breakthroughs in genetic and cellular research have revealed surprising new biological details of the body’s remarkable ability to rejuvenate itself, findings that may give humans a real measure of control over how long and how well they live.
The multitude of genes, processes, and pathways modulating aging in short-lived model organisms provide a plethora of potential targets for drug discovery. Hundreds of genes modulating aging and/or longevity have been identified in model organisms, most of which can be grouped into common pathways and processes like insulin/insulin-like signaling, autophagy, oxidative phosphorylation, and TOR signaling. There is also evidence that life-extending pathways tend to be evolutionarily conserved. For instance, disruption of the insulin–IGF1 pathway has been shown to extend lifespan in yeast, worms, flies, and mice and IGF1R mutations have been associated with human longevity. Thus, evolutionarily conserved life-extending genes and pathways are important targets for drug discovery
SIRT1 is a protein that is believed to play important roles in longevity and age-related diseases. Previous studies have shown that when cells age, SIRT1 expression decreases, while induction and activation of SIRT1 have been associated with extended lifespan. These studies have triggered the search for SIRT1 activators that may be used as dietary supplements to promote health and longevity.
The Cellular Anti-aging Assay (SIRT1 assay) determines the ability of a test material to stimulate SIRT1 protein expression or activity in human cells, which translates to the material’s anti-aging potential.
According to the GenAge database, we now know of >2000 genes that modulate longevity in model organisms, and the drug database lists >400 compounds that can increase longevity in model organisms. Most aging-related genes and pathways have not yet been targeted pharmacologically. Given the volumes of data generated in the life sciences, various approaches in computational and systems biology have been developed to help identify and rank new candidates, identify regulatory genes, and gather biological insights, as reviewed in. Such approaches are imperative, as is the integration of differing expertise in developing and prioritizing targets, drugs, and therapies for testing.
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