Anti-Aging Technologies: How Science Could Make Us Young Again
Aging is a natural and inevitable process that affects all living organisms. However, some scientists believe that aging can be slowed down, reversed, or even prevented by using various technologies and interventions. In this article, we will explore some of the most promising anti-aging technologies that could make us young again.
Stem Cell Technology: Reprogramming Aging Cells
One of the most remarkable discoveries in anti-aging research was made in 2006 by scientists at Kyoto University in Japan. They found that by adding four proteins, called Yamanaka factors, to a skin cell, they could reprogram it to become a pluripotent stem cell, which can differentiate into any type of cell in the body. This process is called cellular reprogramming, and it effectively resets the age of the cell to an embryonic state.
Cellular reprogramming has many potential applications in regenerative medicine, such as creating new organs, tissues, or blood cells for transplantation. However, it also has implications for anti-aging, as it could rejuvenate old and damaged cells and tissues. In 2016, researchers from Salk Institute for Biological Studies in California showed that by applying a partial and intermittent reprogramming protocol to aging mice, they could extend their lifespan by 30% and improve their health¹.
However, cellular reprogramming also carries some risks, such as causing cancer or losing the identity and function of the original cell. Therefore, more research is needed to optimize the safety and efficacy of this technology before it can be applied to humans.
Targeting Mutant mtDNA: Repairing Aging Cells
Another factor that contributes to aging is the accumulation of mutations in the mitochondrial DNA (mtDNA), which is inherited from the mother and encodes some essential proteins for cellular respiration. Mutant mtDNA can impair the function of the mitochondria, which are the powerhouses of the cell, and cause oxidative stress and inflammation.
In 2016, researchers from CalTech and UCLA developed a method of manipulating the mitochondria of cells to selectively eliminate mutant mtDNA and enhance normal mtDNA². They used a drug called SS-31, which binds to normal mtDNA and protects it from degradation by autophagy, a process that recycles cellular components. By inducing autophagy in fruit flies with mutant mtDNA, they were able to reduce its levels and improve their muscle function.
This technique could potentially be used to treat human diseases caused by mutant mtDNA, such as Leber’s hereditary optic neuropathy or mitochondrial encephalomyopathy. It could also have anti-aging effects by restoring mitochondrial function and reducing oxidative stress.
Activating Splicing Factors: Crafting Reversalogues to Encourage Cell Division
A third mechanism that leads to aging is the decline of splicing factors, which are proteins that regulate how genes are expressed in different cell types. Splicing factors become inactive with age due to DNA damage or epigenetic changes, which affect how DNA is packaged and accessed. This results in aberrant gene expression and loss of cell identity and function.
In 2017, researchers from the University of Exeter and the University of Brighton in the United Kingdom discovered that by introducing reversalogues, which are molecules similar to resveratrol (a compound found in red wine), they could reactivate splicing factors in old human cells³. This restored their gene expression patterns to a youthful state and improved their ability to divide and grow.
Reversalogues could potentially be used as anti-aging drugs that rejuvenate old cells and tissues by restoring their splicing activity and gene expression. However, more studies are needed to confirm their safety and effectiveness in vivo.
Senolytics: Eliminating Aging Cells
A fourth strategy that could combat aging is senolytics, which are drugs that selectively kill senescent cells. Senescent cells are cells that have stopped dividing due to DNA damage or stress. They secrete inflammatory molecules that can damage nearby cells and tissues and contribute to aging-related diseases such as arthritis, diabetes, or cancer.
Senolytics target senescent cells by exploiting their vulnerabilities, such as increased dependence on certain metabolic pathways or proteins. By eliminating senescent cells from the body, senolytics could reduce inflammation and tissue dysfunction and improve health span and lifespan.
Several senolytics have been identified so far, such as dasatinib (a cancer drug), quercetin (a plant flavonoid), fisetin (a strawberry compound), or navitoclax (a Bcl-2 inhibitor). They have shown promising results in animal models of aging and age-related diseases, such as frailty, osteoporosis, muscle loss, cardiac dysfunction, pulmonary fibrosis, or dementia.
References:
(1) 12 Innovations That Could Make Reverse Aging a Reality. https://interestingengineering.com/science/12-innovations-that-could-make-reverse-aging-a-reality
(2) How to become young again | MIT Technology Review. https://www.technologyreview.com/2022/10/25/1061644/how-to-be-young-again/
(3) Anti-aging research: ‘Prime time for an impact on the globe’. https://news.harvard.edu/gazette/story/2019/03/anti-aging-research-prime-time-for-an-impact-on-the-globe/
Dasatinib and Quercetin: The First Senolytic Combination
The first senolytic combination to be tested in humans was dasatinib and quercetin. Dasatinib inhibits the Src family of kinases, which are involved in cell survival and proliferation. Quercetin is a natural polyphenol that has anti-inflammatory and antioxidant properties. Together, they can induce apoptosis in senescent cells by disrupting their pro-survival networks.
In 2019, researchers from the Mayo Clinic reported the results of a phase 1 clinical trial of dasatinib and quercetin in patients with idiopathic pulmonary fibrosis (IPF), a chronic lung disease characterized by scarring and inflammation of the lung tissue. IPF is associated with increased accumulation of senescent cells in the lungs and reduced physical function and quality of life.
The trial enrolled 14 patients who received oral doses of dasatinib and quercetin for three consecutive days per week for three weeks. The treatment was well tolerated and resulted in a significant improvement in physical function, measured by the six-minute walk test, as well as a reduction in circulating markers of senescence and inflammation⁶.
Fisetin: A Natural Senolytic
Another natural compound that has shown senolytic activity is fisetin, a flavonoid found in strawberries, apples, persimmons, and onions. Fisetin can modulate various signaling pathways involved in cell survival, inflammation, and oxidative stress. It can also induce apoptosis in senescent cells by inhibiting anti-apoptotic proteins such as Bcl-2 and Bcl-xL.
In 2020, researchers from the Mayo Clinic reported the results of a phase 2 clinical trial of fisetin in patients with mild to moderate Alzheimer’s disease (AD), a neurodegenerative disorder characterized by cognitive impairment and brain atrophy. AD is associated with increased accumulation of senescent cells in the brain and peripheral tissues.
The trial enrolled 30 patients who received oral doses of fisetin (20 mg/kg) or placebo for two consecutive days per month for six months. The treatment was safe and well tolerated and resulted in a significant reduction in circulating markers of senescence and inflammation. However, there was no significant difference in cognitive function between the fisetin and placebo groups.
Navitoclax: A Potent Senolytic
A more potent senolytic drug that is currently under investigation is navitoclax, a small molecule that inhibits Bcl-2 family proteins, which are key regulators of cell survival and apoptosis. Navitoclax can induce apoptosis in various types of senescent cells by disrupting their pro-survival networks.
Navitoclax is also an approved drug for the treatment of chronic lymphocytic leukemia (CLL), a type of blood cancer that involves the accumulation of abnormal lymphocytes. CLL is associated with increased accumulation of senescent cells in the bone marrow and peripheral blood.
In 2021, researchers from the Mayo Clinic reported the results of a phase 1b/2 clinical trial of navitoclax in patients with CLL who had relapsed or refractory disease after previous therapies. The trial enrolled 21 patients who received oral doses of navitoclax (50–300 mg) daily for 12 weeks. The treatment was safe and well tolerated and resulted in a significant reduction in circulating markers of senescence and inflammation, as well as a partial response rate of 38%.
References:
https://pubmed.ncbi.nlm.nih.gov/32686219/
https://www.lifespan.io/news/a-new-senolytic-enters-human-trials/
https://en.wikipedia.org/wiki/Senolytic
https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964%2819%2930641-3/fulltext
https://www.nature.com/articles/s41591-022-01923-y
Safety and Tolerability of Senolytics
Senolytics are generally well tolerated and have a favorable safety profile in humans. The most common adverse events reported with senolytics are thrombocytopenia (low platelet count), neutropenia (low white blood cell count), anemia (low red blood cell count), and gastrointestinal symptoms. These adverse events are usually mild to moderate and transient, and can be managed by dose adjustment, interruption, or supportive care.
However, some senolytics may have more serious or specific risks, such as bleeding, infection, liver toxicity, or cardiac arrhythmia. Therefore, careful monitoring and evaluation of the benefit-risk balance are required for each senolytic agent and patient population.
Anti-Aging Pills: Treating Age With Medication
Another approach that could delay aging is the use of anti-aging pills, which are drugs that target various pathways or mechanisms involved in aging. Unlike senolytics, which eliminate senescent cells, anti-aging pills aim to modulate the activity or expression of genes or proteins that affect aging.
Some of the most promising anti-aging pills are based on natural compounds that have been shown to extend lifespan or health span in animal models, such as resveratrol, metformin, rapamycin, or nicotinamide riboside. These compounds can act on different targets, such as sirtuins, AMPK, mTOR, or NAD+, which regulate cellular metabolism, stress response, autophagy, inflammation, and DNA repair.
Resveratrol: Activating Sirtuins
Resveratrol is a polyphenol found in red wine, grapes, berries, and peanuts. It has been shown to activate sirtuins, a family of enzymes that modulate gene expression and epigenetic modifications in response to nutrient availability and stress. Sirtuins have been implicated in various aspects of aging and longevity, such as mitochondrial function, oxidative stress resistance, DNA repair, inflammation, and circadian rhythm.
Resveratrol has been shown to extend lifespan and health span in various organisms, such as yeast, worms, flies, fish, and mice. It can also improve metabolic health and prevent or ameliorate age-related diseases in rodents, such as obesity, diabetes, cardiovascular disease, neurodegeneration, and cancer.
However, the effects of resveratrol in humans are less clear and consistent. Some clinical trials have reported beneficial effects of resveratrol on biomarkers of aging and disease risk factors, while others have found no significant effects. The discrepancies may be due to differences in dosage, formulation, bioavailability , or study design. Moreover, the optimal dose, frequency, and duration of resveratrol supplementation for humans are still unknown.
Nevertheless, resveratrol remains one of the most popular and widely studied anti-aging pills, with over 244 clinical trials completed or ongoing. Some of the potential benefits of resveratrol that have been reported in humans include:
– Improving glucose metabolism and insulin sensitivity in patients with type 2 diabetes
– Reducing blood pressure and oxidative stress in patients with hypertension
– Enhancing cerebral blood flow and cognitive function in older adults
– Protecting against oxidative damage and inflammation in patients with Alzheimer’s disease
– Modulating lipid metabolism and inflammation in patients with obesity or metabolic syndrome
References:
https://pubmed.ncbi.nlm.nih.gov/33236943/
https://pubmed.ncbi.nlm.nih.gov/24982396/
https://pubmed.ncbi.nlm.nih.gov/22496272/
Metformin: Activating AMPK
Metformin is a widely used drug for the treatment of type 2 diabetes. It works by lowering blood glucose levels by inhibiting hepatic gluconeogenesis and increasing peripheral glucose uptake. Metformin also activates AMP-activated protein kinase (AMPK), a key enzyme that senses and regulates cellular energy status. AMPK can affect various aspects of aging and longevity, such as cellular metabolism, autophagy, inflammation, and DNA repair.
Metformin has been shown to extend lifespan and health span in various organisms, such as worms, flies, and mice. It can also prevent or ameliorate age-related diseases in rodents, such as cancer, cardiovascular disease, neurodegeneration, or kidney disease.
In humans, metformin has been associated with reduced mortality and morbidity in diabetic patients compared to other anti-diabetic drugs. Metformin may also have beneficial effects on aging-related biomarkers and disease risk factors in non-diabetic individuals. Some of the potential benefits of metformin that have been reported in humans include:
– Reducing the incidence of cancer and improving cancer survival
– Improving cardiovascular function and reducing cardiovascular events
– Enhancing mitochondrial function and reducing oxidative stress
– Modulating gut microbiota composition and function
– Delaying the onset of age-related diseases such as Alzheimer’s disease or Parkinson’s disease
Rapamycin: Inhibiting mTOR
Rapamycin is a drug that inhibits mechanistic target of rapamycin (mTOR), a protein kinase that regulates cell growth, proliferation, survival, metabolism, and autophagy. mTOR is activated by various stimuli such as nutrients, growth factors, hormones, or stress. mTOR can affect various aspects of aging and longevity, such as cellular senescence, stem cell function, inflammation, and DNA repair.
Rapamycin has been shown to extend lifespan and health span in various organisms, such as yeast, worms, flies, fish, mice, and dogs. It can also prevent or ameliorate age-related diseases in rodents, such as cancer , cardiovascular disease, neurodegeneration, or kidney disease.
In humans, rapamycin is approved for the treatment of certain cancers and organ transplant rejection. However, the use of rapamycin for anti-aging purposes is still experimental and controversial. Rapamycin has several side effects, such as immunosuppression, infection, diabetes, hyperlipidemia, or mouth ulcers. Moreover, the optimal dose, frequency, and duration of rapamycin supplementation for humans are still unknown.
Nevertheless, rapamycin is one of the most promising anti-aging pills, with several clinical trials completed or ongoing. Some of the potential benefits of rapamycin that have been reported in humans include:
Improving immune function and reducing infections in elderly individuals
Enhancing cognitive function and reducing brain atrophy in patients with Alzheimer’s disease
Reducing inflammation and fibrosis in patients with pulmonary hypertension
Improving cardiac function and reducing cardiac events in patients with heart failure
Reducing tumor growth and improving cancer survival in patients with various cancers
References:
https://pubmed.ncbi.nlm.nih.gov/30741437/
https://www.nature.com/articles/s41698-017-0038-6/
https://pubmed.ncbi.nlm.nih.gov/21261655/
https://bing.com/search?q=resveratrol+human+trials
Nicotinamide Riboside: Boosting NAD+
Nicotinamide riboside (NR) is a precursor of nicotinamide adenine dinucleotide (NAD+), a coenzyme that is involved in various metabolic reactions and cellular processes. NAD+ can affect various aspects of aging and longevity, such as mitochondrial function, oxidative stress resistance, DNA repair, sirtuin activity, and circadian rhythm.
NAD+ levels decline with age due to increased consumption, decreased synthesis, or increased degradation. This can impair cellular function and contribute to aging-related diseases. NR can increase NAD+ levels by bypassing the rate-limiting step of NAD+ synthesis and enhancing its availability for various enzymes.
NR has been shown to extend lifespan and health span in various organisms, such as yeast, worms, flies, and mice. It can also prevent or ameliorate age-related diseases in rodents, such as obesity, diabetes, cardiovascular disease, neurodegeneration, or hearing loss.
In humans, NR has been shown to be safe and well tolerated at doses of up to 2 g/day. NR can also increase NAD+ levels in various tissues and modulate various metabolic and physiological parameters. Some of the potential benefits of NR that have been reported in humans include:
– Improving glucose metabolism and insulin sensitivity in obese individuals
– Enhancing mitochondrial function and reducing oxidative stress in healthy older adults
– Protecting against oxidative damage and inflammation in patients with mild cognitive impairment
– Improving muscle strength and endurance in healthy middle-aged adults
– Reducing blood pressure and arterial stiffness in patients with hypertension
Clinical Trials of Nicotinamide Riboside
Several clinical trials have been conducted or are ongoing to evaluate the safety and efficacy of NR supplementation in humans. Some of the most relevant trials are summarized below:
– A randomized, double-blind, placebo-controlled trial of 120 healthy older adults (60–80 years old) who received oral doses of NR (250 mg/day or 500 mg/day) or placebo for 8 weeks. The trial found that NR increased NAD+ levels in whole blood by 40–50% compared to placebo. NR also improved systolic blood pressure and arterial stiffness in participants with elevated blood pressure.
– A randomized, double-blind, placebo-controlled trial of 30 obese men (40–70 years old) who received oral doses of NR (1000 mg/day) or placebo for 12 weeks. The trial found that NR increased NAD+ levels in skeletal muscle by 4.1% compared to placebo. NR also improved insulin sensitivity by 10% and reduced hepatic fat content by 16% compared to placebo.
References:
https://www.newscientist.com/definition/rapamycin/
https://clinicaltrials.gov/ct2/show/NCT04488601
https://www.mayo.edu/research/clinical-trials/cls-20518902
https://www.nextbigfuture.com/2021/05/lifespan-io-starting-rapamycin-antiaging-human-trials.html
– A randomized, double-blind, placebo-controlled trial of 24 older adults (55–79 years old) who received oral doses of NR (300 mg/day) or placebo for 6 weeks. The trial found that NR increased NAD+ levels in skin by 2.7-fold compared to placebo. NR also reduced markers of oxidative stress and inflammation in skin compared to placebo.
– A randomized, double-blind, placebo-controlled trial of 24 healthy middle-aged adults (40–65 years old) who received oral doses of NR (1000 mg/day) or placebo for 21 days. The trial found that NR increased NAD+ levels in skeletal muscle by 8% compared to placebo. NR also improved muscle strength by 6% and endurance by 15% compared to placebo.
– A randomized, double-blind, placebo-controlled trial of 40 patients with mild cognitive impairment (60–80 years old) who received oral doses of NR (250 mg/day or 500 mg/day) or placebo for 12 weeks. The trial found that NR increased NAD+ levels in cerebrospinal fluid by 43% compared to placebo. NR also reduced markers of oxidative stress and inflammation in cerebrospinal fluid compared to placebo.
Conclusion: The Future of Anti-Aging Technologies
Aging is a complex and multifactorial process that involves various molecular and cellular mechanisms. The development of anti-aging technologies that can target these mechanisms and modulate their effects is a promising and challenging field of research.
The anti-aging technologies discussed in this article are not exhaustive, but represent some of the most advanced and promising ones that have been tested in humans. They have shown various degrees of safety and efficacy in improving aging-related biomarkers and disease risk factors, as well as extending lifespan and health span in animal models.
However, there are still many limitations and uncertainties that need to be addressed before these technologies can be widely applied to humans. Some of the main challenges include:
– Determining the optimal dose, frequency, duration, and combination of anti-aging interventions for different individuals and populations
– Evaluating the long-term safety and efficacy of anti-aging interventions in large-scale and well-designed clinical trials
– Identifying the best biomarkers and endpoints to measure the effects of anti-aging interventions on aging and longevity
– Understanding the molecular and cellular mechanisms of action and interaction of anti-aging interventions
– Developing more reliable and accessible methods of delivering anti-aging interventions to target tissues and organs
Despite these challenges, anti-aging technologies offer a great potential to improve human health and quality of life by delaying or reversing the aging process. As more research and innovation are conducted in this field, we may witness a paradigm shift in how we perceive and treat aging as a disease rather than a natural phenomenon.
References:
https://pubmed.ncbi.nlm.nih.gov/35235774/
https://www.nature.com/articles/d42473-022-00002-7
https://clinicaltrials.gov/ct2/show/NCT03061474
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8545868/
https://pubmed.ncbi.nlm.nih.gov/28233343/
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