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Why Declining Mitochondria Ages You and What To Do About It

Why Declining Mitochondria Ages You and What To Do About It

Mitochondria are highly dynamic organelles that are inside our cells. Their vital role is to be our body's "energy factory," which is crucial for the maintenance of cellular homeostasis, also known as mitochondrial homeostasis. You can think of homeostasis as keeping things in balance. In biological systems, homeostasis is the tendency toward a relatively stable equilibrium between interdependent elements that can be maintained by physiological processes. A good example is shivering and sweating. Mammals maintain a tight regulation of body temperature, so if the ambient temperature is too hot, we sweat; too cold, we shiver - both reactions is our body's attempt to maintain homeostasis.

As you'll soon discover, the communication pathway that ensures that cells have adequate energy supplies (OXPHOS function) and can maintain mitochondrial homeostasis and are supported by a set of "longevity genes" called sirtuins, which promote cellular heath. To work properly, sirtuins need healthy mitochondria.

Current Research on Mitochondria, Aging, and Cellular Homeostasis

It's well-known that we lose mitochondria as we age - this phenomena is considered one of the hallmarks of aging. Despite the importance of maintaining the balance within the cell, there is still controversy as to why mitochondrial homeostasis is disrupted as we get older, and whether this process can be slowed or even reversed. In this post, I summarize and explain an important research study published in the journal Cell that studied the mitochondria of old mice and found evidence that:

  • Although there is some loss of mitochondria during the aging process, it's not nuclear, encoded OXPHOS subunits, the part that provides most of the cells' usable energy.
  • There's a reasonable chance that you can maintain the health of your mitochondria as you age by increasing the levels of an essential coenzyme and activating a group of "longevity genes."

The mouse mitochondrial study presents evidence for an independent nuclear-mitochondrial communication pathway that ensures that cells have adequate energy supplies (OXPHOS function), and can maintain mitochondrial homeostasis. The researchers found that this can happen by reversing the inevitable decline in NAD+ levels as we age that, in part, occurs when one or more of the seven "longevity genes" becomes less active, particularly a gene called Sirtuin 1, or SIRT1.

Now, before you discard the relevance of the findings from research studies on mice to humans, realize that rodents are used as models in medical testing because their genetic, biological, and behavior characteristics closely resemble ours, and many symptoms of human conditions can be replicated in them. Consequently, there's a good chance that just as boosting NAD+ levels in mice activate their sirtuins, which then improve their mitochondrial homeostasis, it may also do that for us.

In a moment, I'll tell you how the scientist elevated the mice NAD+, but first a bit on sirtuins. If you're interested in slowing down the aging process, it would be helpful to learn about these "longevity genes."

Sirtuins at a Glance

As I wrote in NAD+, The Sirtuin Activator That Governs Aging:

  • Sirtuins are a family of proteins involved in regulating cellular processes, including the aging and death of cells and their resistance to stress. Unfortunately, as we age and our NAD+ levels decline, so do our sirtuins.
  • Sirtuins do not simply increase the numbers of mitochondria within the cell; they stimulate the death and destruction of damaged mitochondria and improve intercellular communication. They almost seem to act as a kind of team of proteins, restoring cellular functions to a much higher level of youthful effectiveness.
  • Adequate levels of NAD+ - a coenzyme essential for life, which, as mentioned, also declines as we age - is needed to activate these genes in our body that govern aging, sirtuins.

How does this apply to you? Potentially, this means that you may be able to mitigate a hallmark of aging - mitochondrial deterioration - by acting to increase your NAD+ levels and activate your sirtuins.

Mitochondria Health May Be Restored By Boosting NAD+ and Sirtuin Activity

One of the more surprising findings of the study is the existence of a SIRT1-mediated pathway that regulates mitochondria independently of the commonly known pathway, called PGC-1a/b. The data indicate that when activated, SIRT1 can regulate these two pathways in response to the energetic state of the cell.

How can SIRT1 be activated, you ask? Well, as I already mentioned, by elevating NAD+ levels. The study's authors conclude:

  • Boosting NAD levels in old mice with an NAD precursor restored mitochondrial homeostasis and key biochemical markers of muscle health to levels common in young mice.
  • Increasing NAD might be an effective therapy for "organismal decline with age".

What this means is that the researchers were able to rehabilitate the function of SIRT1 by boosting NAD+ levels enough to restore what would ordinarily be mitochondrial dysfunction, a hallmark of aging. This is good news for those interested in cutting-edge, anti-aging science.

How Can You Increase NAD+ and Activate Sirtuins

Intermittent fasting may help restore mitochondria by increasing NAD+ levels

Given how important sirtuins are for mitochondrial health and healthy aging, you may be interested in how to help them stay activated and robust by keeping your NAD+ levels up as you get older.

You can increase NAD+ by consuming two kinds of NAD+ precursors, a natural plant phenol, and by compressing the time frame during which you eat:

  • NMN (Nicotinamide Mononucleotide) and NR (Nicotinamide Riboside) are two NAD+ precursors that have been tested in various animal models and clinical tests of NR on humans that demonstrate their effectiveness at increasing NAD+. Both NR and NMN are available for sale as food supplements, and are used by many thousands of people.
  • The plant phenol that can upregulate NAD+ and sirtuins is trans-resveratrol, as demonstrated by a November 2016 study that examined how sirtuin-activating compounds could slow aging.
  • That same 2016 study showed that NAD+ and sirtuins can also be activated through caloric restriction, either by a habitual restriction in calories, or potentially via intermittent fasting.

Your Takeaway

When we age, so does our mitochondria, those little, but powerful organelles in our cells that convert the calories we ingest into the energy we need to live. As this happens, our set of "longevity genes" called sirtuins, which are vital for cellular heath, gradually become less active.

The good news is that by keeping our NAD+ levels up, we can support the health and integrity of our sirtuins. Keep these three NAD+ boosters in mind:

  1. Consume NAD+ precursors, such as NMN and NR,
  2. Supplement with trans-resveratrol, and
  3. Restrict the number of calories you consume from time to time, such as through intermittent fasting.


Mouchiroud L, Houtkooper RH, Moullan N, et al. The nad+/sirtuin pathway modulates longevity through activation of mitochondrial upr and foxo signaling. Cell. 2013;154(2):430-441. doi:10.1016/j.cell.2013.06.016

Gomes AP, Price NL, Ling AJ, et al. Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell. 2013;155(7):1624–1638. doi:10.1016/j.cell.2013.11.037

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