Research Summary: Harnessing the Hallmarks of aging


The hallmarks of aging have become an increasingly important target in the research and development of Healthgevity’s novel natural therapeutics. Addressing one or more hallmarks is a core target for formulations within the portfolio.
 Genomic instability
Genomic instability is when the DNA in cells become damaged or mutated, leading to a decrease in cellular function and repair mechanism.
 Telomere Attrition 
Telomeres are the protective caps at the end of each strand of DNA, like the plastic caps at the end of a shoelace.  Over time, telomeres gradually shorten as cells divide.  This process is accelerated by oxidative stress, inflammation and other factors associated with aging.  When telomeres become too short, cells can no longer divide properly and begin to malfunction.  This contributed to many age-related diseases and conditions that become more common as we get older. Telomere attrition is a natural part of aging, but there are ways to slow down the process.
 Epigenetic Alterations 
Epigenetic alterations are changes in the gene expression that are not caused by changes in the DNA sequence.  Epigenetic alterations can be caused by a variety of factors, including environmental exposure, lifestyle choices and aging process itself.  Epigenetic alterations play a role in many age-related diseases and can also affect lifespan and the rate of aging.  Targeting specific epigenetic modifications relates to the potential to slow down aging and improve overall health.
 Loss of Proteostasis 
Proteostasis is the ability of cells to maintain a proper balance of protein levels and structure. When proteostasis is lost, cells are unable to properly control the levels of proteins leading to DNA damage, telomere shortening and age-related diseases.
 Deregulated Nutrient Sensing 
Deregulated Nutrient Sensing (DNS) is a process that occurs as we age, whereby our cells become less able to sense and respond to changes in nutrient levels.  This can lead to a number of age-related health problems, including weight gain, insulin resistance and chronic inflammation.   DNS is thought to be caused by a combination of factors, including changes in the way our cells metabolize nutrients and alterations in the levels of key hormones involved in regulating metabolism.
 Mitochondrial Dysfunction 
The role of mitochondria in energy metabolism is essential for maintaining cellular homeostasis and function.  Mitochondrial dysfunction leads to decreased ATP production, increased ROS production and altered calcium homeostasis, all of which contribute to the development of age-related diseases.
 Cellular Senescence 
Cellular senescence is a process that occurs naturally as we age.  Senescent cells are damaged or deformed cells that can no longer divide, or function properly and also referred to as ‘zombie’ cells.  It is a state of permanent cell cycle arrest that is triggered by stressors such as telomere shortening, DNA damage and oxidative stress.  These cells accumulate over time, and as they do, they start to drag down the performance of our tissues and organs. Senescent cells also secrete proinflammatory signals like IL-6 and IL-8 that damage our bodies further.
 Stem Cell Exhaustion 
Stem cells are responsible for the repair and maintenance of tissues throughout the body, and as we age, our stem cells become less efficient at performing these functions.  This leads to a decline in tissue repair and an increased risk of age-related diseases.
 Altered Intercellular Communication 
As we age, our cells change in many ways, once of the most notable changes is a decrease in the ability to communicate with other cells.  This can lead to a number of age-related problems, including decreased tissue repair, increased inflammation, and reduced immunity.
 Compromised Autophagy
Autophagy is a process whereby cells breakdown and recycle their own components.  This helps to keep cells healthy by removed damaged or unwanted material and it also plays a role in providing energy for the cell during times of stress.  However, autophagy declines with age leading to the accumulation of cellular damage and contributing to the aging process.
 Microbiome Disturbance
As we age, our bodies go through lots of changes. Once of the lesser-known changes is a disturbance of the microbiome- the community of microorganisms that live in and on our bodies.  This disturbance can manifest in a number of ways, including changes in diet, lifestyle and medications which influence the types of bacteria that are present and an overall decrease in the diversity of microbes. 
 Altered Mechanical Properties
Throughout our lives, our bones are constantly remodeling themselves in response to the mechanical stressors we put on them.  However, this process begins to slow down as we age and the altered mechanical properties of our bones can lead to a number of age-related problems such as osteoporosis and fractures. 
 Splicing Dysregulation
Splicing is the process by which RNA transcripts are edited to produce the final protein-coding sequence.  The process is essential for proper gene expression and disruptions to splicing can contribute to the age-related decline in many tissues and organs.
While inflammation is a natural response to injury or infection, chronic inflammation can lead to tissue damage and disease.  During aging, chronic, low-grade inflammation called inflammaging develops which contributes to the pathogenesis of age-related diseases.