Next Generation Anti-Aging Therapeutics

By webnad

As the future unfolds, new and improved therapies aimed to mitigate age-related physiological decline are being developed. Some of these nascent, anti-aging therapies of the future have received attention for conferring beneficial effects on animal models. However, these potential therapies will become relics of the past if they don’t prove effective in humans.

Gene Therapy and Gene Editing 

While our lifestyle choices are the main determinant of how long we live, genetics are estimated to account for 25% of the variation in human longevity. This means if scientists can figure out which genes contribute to longevity — how long we live, gene therapy and gene editing could potentially be used to prolong lifespan. While gene therapy involves adding beneficial genes to cells without necessarily affecting DNA, gene editing refers to direct manipulation of DNA, whereby genes can be added or removed. 

Candidates for gene therapy may have already been discovered and include the BPIFB4 gene variant, observed in long lived individuals, and the klotho gene, shown to increase lifespan and protect against heart and brain aging in rodents. The genes TRT and FST have been tested as an intranasal gene therapy, shown to increase the lifespan of mice. Getting rid of genes with gene editing to prolong lifespan is also a possibility. Deleting the gene for a protein called xCT in mice increases lifespan and improves memory. Removing a gene called KAT7 using a technology called CRISPR-Cas9 also prolongs the lifespan of mice. 

Bioengineered Organs 

Succumbing to a fatal age-related condition like cardiovascular disease or neurodegenerative disease can potentially shorten the duration of our lifespan. Since many age-related diseases with high mortality risks are associated with the dysfunction of a particular organ, replacing a diseased organ could prove to prolong lifespan. While organ transplants have saved many lives, problems arise from limited availability and immune system rejection, especially from older donors. Thus bioengineered organs — organs made in a lab — could provide a readily available alternative to organ donation. While we are far from bioengineering parts of the human brain, we are closer to generating bioengineered hearts and blood vessels, which could potentially prevent death caused by cardiovascular disease and heart failure. 

Cellular Reprogramming 

While still in its infancy, if honed properly, cellular reprogramming technology could be the future of anti-aging therapy. Celluar reprogramming has been shown to reverse the aging of mice and rejuvenate human skin cells by making them 30 years younger. This process is achieved through nobel-prize winning technology, involving what are called Yamanaka factors, which trick older cells into reverting back to an earlier developmental stage, essentially reversing cellular aging. Thus, in the future we may be able to almost literally reverse aging, at least in some organs.  

Stem Cell Therapy

Adult stem cells are the cells responsible for regenerating tissue, like our muscle and immune cells. As we age, stem cells become exhausted and are no longer able to regenerate tissue efficiently. Thus, stem cell therapy could be another way to slow aging by rejuvenating tissue regenerative capacity. Stem cell therapy may give a way to overcome diseases like sarcopenia — age-related muscle weakness and deterioration, which is influenced by defective muscle stem cells. Further into the future, stem cells may even be utilized to replace adult cells. For example, Parkinson’s disease involves the degeneration of a relatively small set of neurons in the brain. Someday, it may be possible to replace these neurons using stem cell therapy. 

Gut Bacteria Transplants 

Fecal matter banking at a young age for future transplantation during older years is a way that scientists have proposed to rejuvenate gut health as we get older. Currently fecal banking is performed to transplant fecal matter from healthy donors to aged individuals with bowel diseases like bacterial infection. Even though transplanting fecal matter from healthy to aged individuals has shown effectiveness in alleviating bacterial infection, scientists have recently proposed banking fecal matter when we are young. By transplanting our younger fecal matter to our guts when we age, we may overcome differences in gut microbes that make immune reactions more likely.

Young Blood Transfusion

The idea that young blood can rejuvenate the old has led to experiments involving heterochronic plasma exchange – injecting aged animals with blood from younger ones. Experiments using mice have utilized this method and shown that infusing blood from young mice into older mice rejuvenates multiple tissues, including the brain, muscle, liver, and bone. Utilizing heterochronic plasma exchange may provide a way to reverse aging, especially as studies come out showing whether this technique is effective in aged individuals.

(Ma et al., 2022 | Cell Stem Cell) Heterochronic plasma exchange, infusing blood from young rodents into older ones, rejuvenates multiple tissues from the brain, to muscle, to liver, and bone.

Another anti-aging development related to blood exchange entails exchanging old blood plasma with saline and albumin – globular proteins found in blood. This “neutral blood exchange” enhances the production of new neurons in the brain, along with the development of new muscle in mice.

An interesting therapeutic development that has taken hold is using umbilical cord blood. The idea behind this strategy is to rejuvenate tissue by infusing blood plasma from an early developmental stage into aged adults. The levels of a metabolite called arachidonic acid declines as people age, but research has shown that rejuvenating the blood supply with umbilical cord blood in rodents increases arachidonic acid levels. Arachidonic acid is just one biological marker of aging, but other studies have shown that injecting umbilical cord blood into aged mice improves their memory and learning capabilities.

From using the blood of young animals to fight aging to banking fecal matter from our younger years, the future is full of new potential treatments for age-related physiological decline. The prevailing questions that will decide whether we invest in these therapies will relate to how cost effective they are.

References
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