Reversing Aging Is No Longer a Pipe Dream - Senolytics are shown to decrease senescent cells, reduce inflammation, and improve frailty in humans

Imagine a future where children and their grandparents are playing together, telling stories, going to the park, riding bikes, learning, and teaching together, a contrast to a common dystopian view of the elderly napping, looking frail, losing their sight and hearing, and getting sick. We are faced with multitudes of factors limiting our quality of life as we age.

As we age, a pain-free, high-functioning existence is not a pipe dream.

Particularly, the role of genetics and the epigenome (gene guardians) have been shown in multiple studies to be key regulators of health and lifespan. In fact, the cellular rejuvenation via modulation gene expression shown in multiple studies was maintained through a differentiation process called induced pluripotent stem cells (iPSCs).

The results showed the next generation of cells were, incredibly, biologically younger somatic cells. Based on this theory, ongoing research shows the reprogramming of old cells results in the transformation of multiple aging phenotypes to a younger state.

This exciting branch of scientific research is exploring a new class of medications that might turn back the hands of time. Not only might we “age in place,” but we might also maintain our cognitive function, disease resilience, strength, and youthful good looks.

Further encouraging research, as described by Andrew Steele in his book, “Ageless, The New Science of Getting Older Without Getting Old,” show that anti-aging properties already exist in nature.

He uses the tortoise’s very long life span of 50-plus years as an example. Not only do they live a long time, but there also appears to be little in the way of degenerative processes in later years. What are those biological factors, and is there a way for humans to capture them to promote extraordinary ageless aging?

As our global population ages, these findings could be considered imperative to learning how to combat and treat aging. This is to ensure not just quality of life but also maintaining high-functioning lifestyles as we age. The cost alone of treating age-related diseases such as cancer, heart disease, and dementia is staggering.

The global human lifespan has increased to 72 years in 2019, and this isn’t just in the developed world. Just 60 years ago, the global human lifespan was 52, in 1960. Would we prefer an extended life expectancy where we play, read, sing, and dance, rather than one where we suffer from complicated medical issues, degenerative diseases, and system failures?

There is huge potential for expanding how we learn to treat aging. In his YouTube discussion of Getting Older Without Getting Old, Andrew Steele shows a multitude of biological factors that contribute to the aging process. Each one has the potential to open a colossal field of medical advancement. These novel cellular and molecular drivers of aging include DNA changes, genetic and epigenetic alterations, senescent cells, changes within our microbiome, malfunctioning protein and mitochondria, and loss of immunity.

Aging Clock Can Be Turned Back By Reprogramming The Cells

Our biology does not always match our chronological age. We may know a vibrant and vital healthy octogenarian whose biological age differs noticeably from the date on their birth certificate. Literature and theories abound about why some folks maintain youthful vigor throughout their later years while others fall victim to the myriad of common age-related distresses. Purpose, lifestyle choices, stress, trauma, diet, exercise, and sleep habits may all be contributing factors to thriving even decades after retirement.

Through decades of longevity research, David Sinclair, a well-known molecular biologist at Harvard Medical School, has discovered ways to evaluate a person’s real biological age at a cellular level. He is dedicated to the study of treating diseases of the elderly and prolonging life. The fact that we are living longer is real. His longevity research is a hopeful glimpse into the future where people live fantastic, healthy, long, and vital lives free from age-related degenerative diseases.

Upon the discovery of induced pluripotent stem cells (iPSCs), scientists have learned to characterize their regenerative ability, noting its similarity to embryonic stem cells which can regenerate to any organ cells in the body.

Based on the theory that the epigenome, the modifiable expression of the genome, is a key regulator of health and lifespan, studies show the ability to reprogram aged cells.

These reprogrammed cells were restored to a younger state and cellular rejuvenation led to further generations of biologically younger cells.  An experiment of inducing cells to transform into iPSCs and injecting them into aging sightless mice, the cells successfully recreated the optic nerve of the mice and remarkably restored sight.

Harnessing the regenerative potential of cells and tissues has bountiful therapeutic use. As we age, damaged tissues may have incomplete repair and function loss. On the other hand, biologically younger cells regenerate quickly and fully after an injury.

A team of researchers, including David Sinclair, published their research report in 2020 about one of their remarkable success stories.

They were able to successfully regenerate the optic nerve in mice, therefore restoring vision. As part of the central nervous system, the optic nerve has notably limited regenerative capacity, which makes this success story even more compelling. Through their longevity research, Sinclair and his team believe they have found the “reset switch” that rewinds the biological clock. They have shown the ability to return cells to their youthful state, reverse aging in the muscles and brains of mice, and continue to research rejuvenation of the entire bodies of mice.

Destroying Zombie Cells (Senescent Cells)

The research into living better for longer has a lot to do with senescent cells.

The cells in our bodies go through their own life cycles. Factors that can harm cells in the body include injury, stress, and disease. When we are young, these damaged cells are cleared by our immune system. As we age, however, our immune system becomes less efficient at removing these damaged cells.

Some of these cells are unique in that they eventually stop multiplying but don’t die off as they should. These cells are known as senescent cells, and they accumulate in the body as we age. In an expanding area of research, senescent cells are being explored in their role in age-related disease, cancer, inflammation, and degeneration.

“Zombie cells,” or senescent cells, have stopped dividing and multiplying like healthy cells. They do, however, continue to release chemicals known as senescent secretomes. In their microenvironment, the compounds secreted by senescent cells play an important role throughout our lives including during development, wound healing, and childbirth. The role of senescent cells is complicated and can be both protective and harmful. As the number of senescent cells increases as we age, they may contribute to age-related degeneration, cancer, and inflammatory diseases.

Over the last several decades, research into cellular senescence has been ongoing. The pursuit of healthier aging hopes to slow down or even reverse age-related health issues.

Published in Nature in February 2016, the article Destroying worn-out cells makes mice live longer showed that eliminating senescent cells in mice extended their lifespans by 20 percent to 30 percent. Senescent cells were killed off in mice over six months. Compared to the control group of mice whose cells were allowed to build up, the mice were healthier with better heart and kidney function. They were also more resilient to stress, more active, and had delayed cancer development.

Senolytic Drug Development

Research has come a long way since those mice were living longer healthier lives in 2016. Imagine a pill that is rejuvenating on a cellular level, literally treating aging rather than the corresponding illnesses related to aging.

This is a big idea, and it is attracting attention from researchers and investors across the globe. A new class of drugs is being pursued that selectively clears senescent cells. Senolytics, or senotherapeutics, target cellular senescence. They hope to address the cause of age-related diseases by taking on aging itself.

Senolytics drugs selectively clear senescent cells. Some of the first senolytic drugs include Dasatinib, Quercetin, Fisetin, and Navitoclax. These range from plant-based compounds to anti-cancer medications.

In preclinical studies, the senolytics delayed, prevented, or alleviated frailty and cancers as well as disorders of the liver, kidney, lung, eye, musculoskeletal system, cardiovascular system, and neuropsychiatric issues.

The agents targeted mechanisms of aging that are the contributors or root causes of multiple disorders with the hope of potentially relieving over 40 conditions. From these early pilot trials, senolytics are shown to decrease senescent cells, reduce inflammation, and improve frailty in humans. Future clinical trials for Alzheimer’s disease, osteoarthritis, osteoporosis, age-related eye diseases, diabetes, bone marrow transplant, and childhood cancer survivors are underway or beginning.

While not a new name in medications, there is evidence metformin may also combat age-related disorders. Metformin treats high blood sugar levels caused by type 2 diabetes. A large clinical trial, targeting aging by metformin (TAME), is underway.

It has been found that metformin, a biguanide, combats age-related disorders, improves health span, and has age-targeting effects on biological aging. Discovered in 1922, metformin has been in use since 1995 in the US and is listed as an essential medicine by the WHO. For these reasons, this clinical trial aims to review metformin’s age-related mechanisms such as improving nutrient sensing, lowering telomere attrition, protecting against macromolecular damage, delaying stem cell aging, modulating mitochondrial function, and lowering senescence. Because metformin may improve overall health as well as provide age-targeting effects, it is an attractive gerotherapeutic for humans.

While We Wait For Senolytics

It may seem farfetched to reverse the aging process by taking a pill or medication. Dedicated longevity researchers are focused on helping the human population live longer lives more healthily and happily. Incredibly, it may be within the next 5 to 15 years that these medicines are available on a large scale. Currently, experiments with these medicines have shown mice regrowing fur and regaining faster running abilities. Researchers have started preliminary human trials that, at least in theory, show potential in treating many age-related issues, if not aging itself.

Currently, the ground is set to explore a vast arena of medical research. The implications are enormous. People who have mastered skills and amassed unfathomable knowledge could stay in the workforce, contributing to untold success. Grandchildren and grandparents could play, learn, and teach each other while building stronger, healthier relationships. At the very least, it would be possible to maintain exceptional vision, hearing, mobility, strength, and function while remaining pain-free and without disease for longer.

In the meantime, there are many ideas on what we can do to minimize the effects time plays on our biological clocks.

It may help to take rejuvenating supplements such as curcumincollagen, and resveratrol while eating a healthy diet full of vitamins, minerals, and compounds that are known to support the body. Reducing stress with high-quality sleep and meditation practice is noted to slow down our biological clock. Exercise, get outside, and stay strong to reduce the risk of age-related injury that can lead to hip and knee replacement.

There is an old saying: when someone ages, his heart or brain ages first. This is true. Maintaining cognition while having a strong sense of purpose has also shown to be a great indicator of a healthier long life. A collection of 20 years of scientific research has shown that an individuals’ view on aging can significantly determine longevity and long-term health. The results provide insight that holding a positive view of aging that includes the growth and gains in wisdom, patience, dignity, sense of maturity, and freedom has a significant impact on healthy aging. Dr. Michael Gregor, on his best diet for healthy aging, says, “it may not be about adding years to your life, but life to your years”.

Perhaps each one of us wishes we could provide a health-promoting longevity pill to a loved one right now. Restore their age-related vision loss, repair their mobility, or recover their memory and cognitive function. While the incentives to either move forward or delay this type of research are many, is there anyone who would not wish to improve the lives of their elders?

About the Author: Dr. Yuhong Dong, a medical doctor who also holds a doctorate in infectious diseases in China, is the chief scientific officer and co-founder of a Swiss biotech company and former senior medical scientific expert for antiviral drug development at Novartis Pharma in Switzerland.



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