Hallmarks of Aging: An expanding Universe

The Hallmarks of aging are the cellular failures that longevity scientists agree ultimately drive the entire aging process. Originally published in 2013, the groundbreaking ‘Hallmarks of Aging’ paper has been updated this year to include 3 new hallmarks of aging and details the developments in our understanding of the original hallmarks. The paper titled ‘Hallmarks of aging: An expanding universe’ now includes loss of autophagy, chronic inflammation and dysbiosis of the gut microbiome as three new hallmarks contributing to the aging process.

This article will detail each of the new hallmarks and how increasing NAD+ levels with an NAD supplement such as Nuchido TIME+ can positively influence them.

Hallmarks of Aging

Loss of Autophagy

Autophagy literally means ‘self-eating’ and is the cell’s internal recycling system. When key structures in the cell such as proteins and mitochondria become, damaged autophagy is activated to breakdown and recycle the damaged cellular components. Autophagy is critical to maintain cellular health because damaged cellular machinery cannot function correctly, this causes cellular damage including a decline in energy production, decreased cellular repair and increased production of toxic molecules.

During aging autophagy declines, allowing an accumulation of damaged structures within the cell and other ‘cellular junk’ which drives aging. One of the key pathways that stimulates autophagy is AMPK. AMPK Activity declines during aging, but you can activate AMPK by creating energy stress in your cells via exercise and fasting or by supplements.

NAD+ and SIRT1 are known to directly activate autophagy and mitophagy (the recycling of damaged mitochondria) and also activate AMPK to further stimulate cellular repair and longevity. Several of the ingredients in Nuchido TIME+ are also known AMPK activators.


Chronic Inflammation

Inflammation is part of the immune system, it signals damage or threat to the body and triggers a reaction to fix it. In this manner inflammation is very controlled, it occurs for short periods of time to act as a signal and is then turned off again. Inflammation becomes damaging when it becomes uncontrolled and inflammatory factors are released even when they are not needed, such as during aging. It is so important in aging that it is referred to as ‘inflammaging’.

Chronic inflammation is strongly linked to other hallmarks of aging which create an environment that promotes excessive inflammation within our body e.g., increased numbers of senescent cells secrete pro-inflammatory factors which trigger other cells to also become senescent and excrete pro-inflammatory factors.

Chronic inflammation causes damage to cells and tissues, for example in the skin it promotes the breakdown of collagen and elastin leading to signs of skin aging.

NAD+ is known to activate anti-inflammatory pathways, to ensure that inflammation is only activated when needed. NAD+ decline during aging also contributes to loss of cellular repair which promotes cells to become senescent.


Gut Dysbiosis

Your gut contains trillions of bacteria which form the gut microbiome. This plays an important role in digestion and absorption of nutrients from food. We now also know that the gut microbiome can impact the whole body. For example, the gut microbiome is known to communicate with the brain, skin and other organs while also influencing levels of inflammation.

Some gut bacteria are beneficial and support your health, while others can be negative and promote chronic inflammation and accelerate aging. Therefore, disruptions to the balance of the gut microbiome can negatively impact health and contribute to aging.

Studies show that during aging there is a reduction in the diversity of the gut microbiome, with an increase in pro-inflammatory bacteria and a reduction in beneficial bacteria, such as those which strengthen the gut barrier. There is also a reduction in gut barrier integrity, which further promotes inflammation. Overall, causing disruption to the functions of the gut and accelerating aging across the whole-body.

Studies show there is a symbiotic relationship between NAD+ and the gut microbiome. NAD+ supports energy production within microbes and is required for enzymes that support microbial survival and reproduction. While the microbes present in the gut have been shown to contribute to cellular NAD+ production.

Additionally, a recent human study showed that increased NAD+ levels improved gut composition by increasing levels of beneficial bacteria.


A key feature of the paper is also its discussion of how interconnected all of the hallmarks are.

All the 12 Hallmarks of Aging are strongly related to each other. Indeed, a notable feature of effective anti-aging interventions is the diversity of mechanisms by which they target different aging hallmarks in different tissues to maintain healthspan of the whole organism.”

This continued research highlights why the best approach to slow aging is to target multiple hallmarks simultaneously. Excitingly, studies continually show that NAD+ is a molecule which can positively impact all the Hallmarks of Aging to improve cellular health. Read our other blogs to learn more about the other Hallmarks of Aging.