Since long, scientists have advanced the idea that changes to DNA cause aging; however, that doesn’t fully explain why certain people age faster than others.
Sinclair and her team discovered that cell damage and epigenetic changes accelerate aging, providing support for a theory suggesting that it occurs as the result of gene expression imbalance, not genetic code itself.
Epigenetics
For decades, scientists believed that genes encoded within our DNA were the sole determining factors of how long we live. But new research shows that epigenetic changes — which alter how cells read our DNA — may also play an impactful role in speeding up or delaying aging processes.
Epigenetics refers to a set of processes that govern how genes are activated or deactivated. Although our genomes remain constant across every cell in our bodies, epigenetic changes we experience affect which cells become skin, nerve, or muscle cells – as well as how quickly our cells grow or produce proteins.
Epigenetic changes are caused by non-genetic factors, including diet, sleep patterns, stress levels and environmental exposures. They may pass from parent to offspring allowing a form of inheritance outside our genetic code; but can also be reversed.
Our bodies need to be able to adjust to an ever-evolving environment. When we are hungry, for example, our bodies may adapt by epigenetically tuning metabolism and growth for energy conservation; if these adjustments prove maladaptive however, they could lead to disease.
Scientists have long understood that epigenetic changes can result from life events like trauma or poor diet, yet were unclear as to whether these were driving aging or simply following it. In Sinclair’s team’s new study, temporary DNA breaks were caused in mice in order to mimic low-grade, ongoing damage that mammalian cells experience due to exposure to UV rays, cosmic rays, chemicals or other stressors during normal cell division processes and as a result of other stressors such as UV light. This method could easily follow it and drive further aging.
Researchers discovered that just a single episode of epigenetic damage to mouse cells caused them to act and appear as older mice, yet restoring their epigenetics restored youthful gene expression patterns and changed chromatin structures that control which genes were active.
Results have revealed that reversing epigenetic changes could be key in slowing or reversing biological aging. To better understand this phenomenon, the team is currently investigating how this restoration occurred and hopes that this knowledge can provide a basis for developing drugs or lifestyle interventions that target these mechanisms and extend human lifespan.
NAD+
Animal studies have demonstrated how NAD+ can reverse aging, by increasing DNA repair and slowing mitochondrial dysfunction deterioration. It has also been found to promote longevity by activating sirtuins which protect against age-related disease while increasing longevity. Scientists are exploring methods for increasing NAD+ production within humans in hopes that it may one day provide a cure for numerous chronic illnesses.
NAD+ is an essential molecule involved in many essential processes, including energy production, signaling, and metabolism. Found in virtually every cell in our bodies and required for producing ATP to fuel all cellular functions; its enzymes also protect against oxidative damage while regulating gene activity – all while improving sleep patterns and exercising capacity as well as anti-ageing benefits like maintaining healthy immune systems and glucose tolerance. This molecule has also been linked to numerous health benefits like improved sleep patterns or exercise capacity increases; its anti-ageing benefits also make this essential molecule indispensable.
NAD+ levels decline with age and are linked to several age-related diseases. Clinical trials utilizing precursors like nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) to restore NAD+ levels have attempted to address this decline, however none have replicated the favorable health outcomes observed in preclinical models, suggesting that NAD+ depletion in humans may be more complex than initially assumed.
UNSW Laboratory for Ageing Research recently conducted a clinical trial and discovered that supplementing with NMM significantly raised NAD+ concentrations among 33 participants aged 20-80 years. Their results were published in Nature Communications.
At four time points over two weeks, participants in this trial consumed orally administered NMN and its effect measured in their plasma at four time points over two weeks using Student’s Paired T-test analysis. Analysis by this test demonstrated that NMN led to significantly higher whole blood NAD+ concentrations compared to placebo at every timepoint; and significant changes were seen with SIRT1 protein expression levels in PBMCs as well as pro-inflammatory cytokine production levels in plasma. A crossover design provided particularly powerful statistical power given individuals’ differing responses as well as large variations between individuals’ baseline NAD+ levels.
CRISPR
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is an innovative technique that combines DNA-editing technology and an ancient adaptive immune system found in bacteria to modify genes. CRISPR was initially created as an antiviral measure against viruses; today scientists use it to alter genes directly inside living cells by targeting specific sequences with an RNA guide guiding Cas9 protein which cuts DNA at specific parts of genome, enabling scientists to add or delete bits as needed.
Researchers have already utilized this tool to target genes involved in cancer, but its capabilities extend far beyond this field. By disabling a gene, scientists could prevent cells from producing too much of a specific protein and ultimately treat conditions like Parkinson’s and Alzheimer’s more effectively.
Scientists have also employed CRISPR technology for other forms of gene editing, such as altering single bases within the genome. This process, known as base editing, allows researchers to change genetic codes by replacing letters such as C with T or A with G — making gene modifications less invasive than surgery that involves cutting through entire genomes.
scientists have recently applied CRISPR technology to stem cells. Stem cells are unspecialized cells that can develop into more specialized ones like neurons and heart muscle. By increasing old stem cell’s ability to produce new, younger ones, scientists have demonstrated that mice’ ageing process could be reversed through increasing this process.
A new study published in Cell demonstrates how degradation of epigenetic information leads to ageing in mice, and that restoration of this information can reverse it. Researchers used CRISPR to locate genes influencing cellular senescence (the process by which cells cease dividing and become damaged) before inactivating KAT7 gene, leading to younger-looking and acting mice.
Scientists hope that in the future they will apply this technology to human stem cells found throughout our bodies that have the capacity to differentiate into many different tissues, an essential step toward creating effective therapies to prevent age-related diseases and slow chronic illnesses from progressing further.
Yamanaka Factors
Discovering that adult cells can revert back into embryonic states has revolutionized cellular biology, leading to unlimited production of specialized cells for use in regenerative medicine and other applications. This Nobel prize-winning discovery allows scientists to make use of this groundbreaking knowledge. Reprogramming can also assist researchers in understanding the process of aging and developing drugs to slow or reverse it, although such drastic reprogramming may also have detrimental side-effects such as complete dedifferentiation. Researchers are exploring ways to uncouple these processes so as to take advantage of reprogramming without dedifferentiation, known as epigenetic rejuvenation technology, and thus extend human lifespan and organ health.
The Yamanaka factors are four genes that can reprogramm somatic cells into pluripotent stem cells (iPSCs). They are highly expressed in embryonic stem cells and can induce pluripotency in human somatic cells as well as regulate key developmental signaling pathways – likely initiating most, if not all pathways necessary for inducing an iPS cell state.
Scientists have recently demonstrated that Yamanaka factors can delay cell senescence and decrease tumor cell growth rates, even suppressing certain types of cancer such as sarcomas. Further research must be conducted in order to identify the specific pathways regulated by these transcription factors as well as any effects they might have in combination with other reprogramming factors like CHD4 which is also involved in this reprogramming process; overexpression is linked with larger size tumors and resistance to chemotherapy treatments.
Yamanaka factors can also boost tissue regeneration in vivo. According to research conducted on mice, researchers observed that short-term expression of Yamanaka factors accelerated muscle regeneration by activating satellite cells and secreting Wnt4 for maintaining SCs in quiescent states thereby aiding muscle regeneration. Reprogramming factors may increase regeneration by altering their microenvironments which is an integral component in determining their potential regeneration abilities.
