It could be said that all phases of an organisms birth, growth, decline and even timing of death serve to maintain the stability and preservation of its DNA. DNA is life and life is DNA. The importance of maintaining the integrity of over 3 billions base pairs to produce a human being should be viewed as the ultimate function of a cell’s life. Modern man has been said to arrive on the earthly scene some 300,000 years ago and throughout that time our DNA sequence has been faithfully replicated to ensure survival.
Our earthly environment presents a multitude of opportunities to destroy this DNA message, however, our cells have created numerous mechanisms to protect and fix DNA in order to maintain the code (1). When a cell loses that ability to maintain the code it starts to age and eventually goes into senescence or dies via programmed cell death which is called apoptosis. Mitochondria also have DNA and there are similar mechanisms to repair that DNA (2).
True stability results when presumed order and presumed disorder are balanced. A truly stable system expects the unexpected, is prepared to be disrupted, waits to be transformed.
Tom Robbins
Many of us have heard of the premature aging syndromes such as the progeria syndromes where a child ages prematurely, suffering from diseases usually seen in the elderly. Their DNA problems arise from a broken nuclear architecture, collectively termed laminopathies, in addition to defects in the DNA repair pathways (3). Laminopathies basically refer to the scaffolding that DNA uses to support DNA replication and division. When the scaffolding malfunctions then the DNA is unable to replicate properly and can lead to these rapid aging syndromes.
There are multiple DNA repair mechanisms mediated by numerous proteins. Of the mechanisms related to aging two family of proteins stand out, the Sirtuins and the PARPs (Poly (ADP-ribose) polymerases). Sirtuins are a family of proteins that have a wide range of activities that include, transcription regulation, energy metabolism, DNA repair, inflammation and circadian rhythm regulation (3). PARPs are a family of proteins that function to repair DNA, cell proliferation and regulate cell death (4).
Both the sirtuins and PARPs use NAD+ for energy and we know that NAD+ decreases as we age. The reason NAD+ decreases as we age have been linked to increased population of senescent cells (i.e., cells that have reached their Hayflick limit) (4). As cells divide and the number of senescent cells increase in the body, these cells release senescence associated secretory phenotype (SASP). SASP is a collection of inflammatory molecules (cytokines and chemokines) that when released increase the activity of CD38 (5). CD38 is an enzyme that degrades NAD+ leading to its depletion in our cells as we age.
Lower levels of NAD+ may lead to genomic instability since the proteins that fix the DNA don’t have the energy they need. Supplementation with nicotinamide mononucleotide and NR may improve DNA repair by increasing NAD+ levels which in turn help to support PARP and sirtuins activity.
So what else can we do to improve our sirtuin and PARP activities? It can be as easy making sure you get enough sleep. It is said that sleep allows your body to heal and to regenerate itself. When we are active during the day, out in the sun, eating, drinking and exposing ourselves to other potential DNA damaging events our cells need time to recover and repair. Sleep allows our cells the time to take a break from the activities of daily living and heal itself particularly when it comes to nerve cells. This effect is seen across species from fish to mice and most likely in humans (9, 10).Getting 7-9 hour of sleep is always recommended for good health (11).
Next Read: Cellular Senescence – Hallmark #7