Aging is a universal experience

From the time we are born, the aging process starts to cause a multitude of changes to our bodies.
Some age-related changes are relatively painless and mild, such as graying hair. Others result in reduced physical function and increased vulnerability to disease, frailty, or disability.
Advancing age is a major risk factor for numerous chronic diseases.

Cellular malfunction drives aging

Aging is the result of a breakdown in the function of cells, which then restricts the body’s ability to operate properly. This breakdown is caused by a range of influences, both internal (genes, infection, inflammation) and external (environmental), that we are exposed to throughout our lives.

These stimuli can damage cells, and as the damage mounts, we display the ‘hallmarks of aging’.

Hallmarks of aging

Scientists have identified the hallmarks of aging as a core range of nine genetic, molecular and cellular factors that determine the rate and extent of the aging processes across different organisms (with an emphasis on mammals).

They manifest during normal aging and accelerate aging if induced or aggravated. Most importantly, they decelerate aging if they are prevented or blocked, resulting in increased healthspan and lifespan.

Here are the nine hallmarks of aging:

Genomic instability

Every cell in your body contains DNA that defines your individual genome. Proper functioning of your genome is largely responsible for the smooth running of your body, however it suffers constant damage from both external sources (like radiation or pollution) and internal sources (such as free radicals).
Encoded within DNA is a number of processes that detect damage, but the repair is not always perfect, and damage to our genome accumulates. As repair mechanisms fail to correct DNA damage, mutations accumulate and lead to aging and disease.

Telomere attrition

Telomeres at the ends of chromosomes, like all other sections of DNA, are prone to DNA damage. But, unlike the rest of the chromosome, telomere damage is not fixed by the DNA repair pathway as this would lead to fused chromosomes and genomic instability.
As cells divide, the telomere ends of chromosomes get shorter. Eventually, the enzyme that adds telomeric repeat sequences (telomerase) gets silenced. So, telomeres get progressively shorter with age and eventually the telomeres are too short for cells to divide.
Progressive shortening of telomeres leads to senescence, apoptosis, or oncogenic transformation of somatic cells, which negatively affects both health and lifespan.

Epigenetic alteration

Epigenetic alterations are modifications in the chemical structure of DNA that does not change the DNA coding sequence. They occur in the body when chemical groups (called methyl groups) are added to or removed from DNA or when changes are made to proteins (called histones) that bind to the DNA in chromosomes.
These changes can occur with age and exposure to environmental factors such as diet, exercise, drugs, and chemicals. Epigenetic alterations turn on pro-aging genes and turn off youthful ones, which leads to a system-wide loss of function.

Loss of proteostasis

Proteostasis is the cellular process that produces and breaks down the proteins that the body needs.

As cells age, environmental stresses add up and mechanisms responsible for maintaining proper protein composition start to decline. Proteins lose their stability, autophagic processes start to fail, and misfolded proteins accumulate. Misfolded proteins not only fail to perform their normal job, they can clump together, become toxic, and allow harmful by-products and cell damage to accumulate.

Deregulated nutrient sensing

Metabolism and its byproducts, over time, damage cells via oxidative stress, mitochondrial dysfunction and other factors. Too much activity, and changes in nutrient availability and composition cause cells to age faster. Therefore, organisms depend on multiple nutrient sensing pathways to make sure that the body takes in just the right amount of nutrition.
Damage to the nutrient-sensing molecules deteriorates cells’ response signals, which in turn impairs energy production, cell growth and other foundational functions. Age-related obesity, diabetes and other metabolic syndromes can all be a product of deregulated nutrient sensing.

Mitochondrial dysfunction

Mitochondria are hugely important to energetic and cellular processes – they are responsible for generating ATP, act as sensors of cellular distress, and they are the first parts of the cell to send and respond to cell death signals.
As cells age, their mitochondria start to lose their integrity due to the build-up of oxidative stress. Compromised mitochondrial function leads to less efficient energy creation, contamination of previously unaffected mitochondria, and elevated oxidative stress.

Cellular Senescence

Cellular senescence is the stage at which cells lose their ability to grow and divide, which can occur due to damage, or as a result of a loss in molecular components.
Aging of the immune system results in its diminished capacity to remove senescent cells, which accumulate with age and secrete damaging molecules and inflammatory signals into the surrounding areas.
Accumulation of senescent cells in tissues of humans is thought to contribute to the development of ageing-related diseases, including Alzheimer's disease, type 2 diabetes, and various cancers.

Stem cell exhaustion

The ability of the body to regenerate tissues and organs depends on healthy stem cells in almost every tissue. As we age, our stem cells eventually lose their ability to divide, and we cannot replace the stem cells that have changed or died.
Stem cells are the ultimate source of new cells. Compromised ability to replace or renew stem cells leads to their overall decrease in the body, which can trigger age-related disorders such as a weakened immune system and deficient tissue repair.

Altered intercellular communication

As they age, cells change their communication habits and become more focused on self-preservation, which can lead to damage elsewhere.
Loss of appropriate communication among cells and tissues is a product of the other hallmarks of aging – senescent cells in particular. It can trigger chronic inflammation that can further damage aging tissues.

The science of aging well

Due to the myriad biological factors that influence it, no single mechanism can prevent aging. Yet research has demonstrated that the rate of aging can be slowed by mitigating, delaying, or even reversing cellular damage.

At Seneque, we are working to develop the most effective ways to optimize NAD+ levels to increase the portion of life spent in good health and extend longevity.

Finding ways to keep cells youthful using methods such as NAD+ boosting with NMN is an area of enormous potential; one which we are exploring via our extensive pipeline of ongoing preclinical and clinical research.
Targeted treatment of the cellular causes of aging will enable us to slow the appearance – and reduce the burden of – age-related diseases, and provide solutions that allow everyone to go through the universal human experience with increased healthspan and lifespan.