Understanding the hallmarks of aging
Aging is a complex and multifaceted phenomenon. The Hallmarks of Aging are those pathways that underlie human aging, represented within their three respective groups: primary, antagonistic and integrative.
Primary hallmarks of aging are the foundational causes of cellular damage. These are mainly related to the accumulation of DNA mutations and the impact of misfolded proteins with age. This damage triggers a dysregulation of cellular metabolism and an accumulation of senescent cells, which represent the antagonistic hallmarks of aging. These in turn cause integrative impacts, such as increased chronic inflammation throughout the body.
It is the combination of primary and antagonistic hallmarks which leads to the functional declines that are commonly observed in aging. Our goal is to develop and invest in therapies that prevent or reverse each of these hallmarks of aging, thereby expanding healthspan and promoting overall health and well-being as people age.
As cells age, their chromosomes become less stable and their DNA accumulates damage and mutation. DNA repair mechanisms also start to fail which leads to more mutations and promotes aging and disease
Senescent cells are cells that should have died and been destroyed as part of normal turnover, but instead they stay alive and start making many proteins that negatively affect other cells in their surroundings (so called “zombie cells”), which cause multiple associated diseases. With age, humans accumulate senescent cells, which is something Rejuveron wishes to prevent.
Telomere is the name given to the ends of each human chromosome, which makes up an individual’s DNA. As cells divide, telomeres get shorter until they become too short, causing cells to age and stop functioning properly.
Deregulated Nutrient Sensing
High metabolic activity can put stress on human cells and cause them to age. However, when cells have limited nutrients available, they enter a regenerative mode, a state which has been shown to increase lifespan in mice. Mimicking this process with small molecules has the potential to increase health and lifespan in humans too.
Mitochondria are the powerhouse of cells, as they use nutrients to make energy that enables people to live. However, with age, they build-up oxidative stress, mutations, and lose their integrity, which leads to cellular dysfunction and aging.
Stem Cell Exhaustion
With age, stem cells lose the ability to differentiate and replace cells throughout the body. This is particularly important in the bone marrow where stem cells give rise to blood and immune cells and where the exhaustion of stem cells leads to a weak immune system, making the aged population particularly vulnerable to infection.
As cells are exposed to environmental factors, their DNA is subtly modified through epigenetic mechanisms. These changes accumulate over time, promoting alteration of gene expression which underlies several aging-related diseases.
Loss of Proteostasis
Our cells are constantly renewing proteins by degrading old proteins and making new ones. When these autophagic processes start to fail, damaged and misfolded proteins accumulate in cells, leading to cellular death and aging.
Altered Intercellular Communication
As cells age, they show an increase in self-preserving signals as opposed to adequate chemical communication with their neighbors. For example, aged cells that become senescent will trigger chronic low-grade inflammation (so called-inflammaging) which contributes greatly to the aging process.
Macroautophagy involves the containment of cytoplasmic material into vesicles, whose contents are later digested or broken down into parts by lysosomes. As reduced organelle turnover and degrade, it contributes to aging and aging-related dysfunction or declines.
Evidence suggests a bidirectional and cyclical relationship between chronic inflammation and the development of age-related conditions, such as cardiovascular diseases, neurodegeneration, cancer, and frailty.
Dysbiosis is characterized by a change in microbiota. Such an imbalance in natural colonies of microflora inside the human body can lead to a range of diseases and contribute to aging.
Our Diversified Portfolio
We make healthy aging a reality by building portfolio companies focused on treatments for healthy aging. Our goal is to create a platform of portfolio companies that will lead to optimal exit scenarios after successful development, making space so that we can continue to create new portfolio companies.
This specific platform model approach spreads the risk across a variety of technologies and approaches, while providing synergies that could accelerate the speed to market in this growing field of longevity.