Mitochondria are organelles found in cells that produce energy through oxidative phosphorylation. They play a key role in numerous cellular processes and are involved in aging. Mitochondrial biogenesis generates new mitochondria and regulates mitochondrial content in cells. During aging, mitochondrial function declines which can negatively impact organ function. Mitochondrial alterations are seen in aging tissues and are associated with mutations, dysfunction, and inflammation. Supporting mitochondrial biogenesis and function through diet, exercise, and supplements may help prevent age-related diseases and support healthy aging.

1. UNDERSTANDING
MITOCHONDRIAL
HEALTH AND AGING

2. The mitochondrion—or mitochondria, in
its plural form—is a specialized
organelle found in most eukaryotic
cells –cells that contain a nucleus.
These organelles are often referred to
as a cell’s energy power plant.

3. Because they help provide energy to the cell, mitochondria
are vital for human survival.They are involved in numerous
cellular processes that rely on energy nourishment—such
as cell growth, cell messaging, replication, and aging—and
they’re unique in their ability to auto-replicate. Since they
play an essential role in numerous diseases and are
particularly important in the process of aging, mitochondria
are now known to be more than just the center of energy
metabolism.

4. MITOCHONDRIA &
MITOCHONDRIAL BIOGENESIS

5. MITOC H ON D R IA &
MITOC H ON D R IA L B IOGEN ESIS
The primary function of
mitochondria is to produce
adenosine triphosphate (ATP). This
is done through the process of
oxidative phosphorylation through
the respiratory system, which
synthesizes more than 95% ATP for
cellular utilization. Mitochondria also
play an essential role in amino acid
and lipid metabolism, calcium
homeostasis, regulation of
apoptosis, cell cycle regulation, and
thermogenesis.2

6. Mitochondrial biogenesis is a multi-stage process that generates new
organelles, which regulate the mitochondrial content within the cell.
Mitochondrial biogenesis can be defined as the growth and division of pre-
existing mitochondria.3 It’s mainly influenced by environmental stress, such
as exercise, caloric restriction, low temperature, oxidative stress, cell
division and renewal, and differentiation. Mitochondrial biogenesis is
accompanied not only by variations in number but also in size and mass.
Mitochondria play a major role in inflammaging and in the activation of
NLRP3 inflammasome. Inflammaging refers to the chronic, low-grade
inflammation that characterizes aging. Most activators of the NLRP3
inflammasome induce the generation of mitochondrial reactive oxygen
species (ROS).

7. When mitochondria are damaged, it triggers the release of two
very potent pro-inflammatory molecules (cytokines): interleukin (IL)-1β and
IL-18.These molecules are powerful activators of the innate immunity (non-
specific defense mechanisms that come into play immediately or within
hours of an antigen's appearance in the body) and NLRP3 inflammasome.
Cardiolipin, which is found only in mitochondria and bacteria, can activate
the proinflammatory pathway of the NLRP3 inflammasome upon
mitochondrial dysfunction.
The NLRP3 inflammasome has been known to be an unexpected marker of
stress and metabolic risk and has been implicated in the development of
major aging-related diseases such as gout, type 2 diabetes, obesity, cancer,
and neurodegenerative and cardiovascular disorders.

8. MITOC H ON D R IA &
MITOC H ON D R IA L B IOGEN ESIS
Among the factors already known
to affect the aging process, the failure
and decrease of mitochondrial
biogenesis seems to employ some
of the most potent effects on the
organism. If biogenesis is affected, a
slower mitochondrial is expected
along with the accumulation of altered
lipids, proteins and DNA must also
increase, further affecting the
situation.

9. HOW DO MITOCHONDRIA
EFFECT AGING?

10. Mitochondrial alterations have been extensively described in aging tissues
of many organs.They have been particularly studied in heart conditions, but
also in organs like the liver, brain, and adipose tissue. A key reported feature
of aging mitochondria was the presence of mutations, which are responsible
for mitochondrial dysfunction.4
Additionally, aging comes with a decline in mitochondrial function, and this
decline can negatively impact how our internal organs function as we
age.5 Together with mitochondrial dysfunction, chronic inflammation is
another hallmark of both aging and degenerative diseases.At the same
time, aging is associated with inflammaging, which involves several tissues
and organs, including the gut microbiota.6

11. SUPPORTING THE MITOCHONDRIA
FOR HEALTHY AGING

12. SU PPOR TIN G TH E MITOC H A N D R IA
FOR H EA LTH Y A GIN G
In mammals, the most important factors involved in
mitochondrial biogenesis are the thyroid hormones.
Levels of T3 and T4 hormones have been observed
as important factors in the maintenance of proper
mitochondrial health during aging.
But it is important to keep in mind that the
effectiveness of thyroid hormones on specific
tissues can vary under different physiological
conditions. For instance, T3 can increase
mitochondrial biogenesis in oxidative rat muscle but
not in glycolytic muscle, and this differential
response correlates with lower amounts of TH
receptors in the glycolytic tissue.

13. A variety of other approaches are being considered to alleviate deficits in
mitochondrial activity and biogenesis during aging. For example, it has been
observed that several conditions that promote survival—such as vitamin E
dietary supplementation, calorie restriction, polyphenols, and moderate
physical exercise—ameliorate mitochondrial dysfunction in aging. Particularly,
resveratrol and exercise have been shown to increase the activity of
mitochondrial biogenesis.
Mitochondria initiate multiple processes leading to age-associated deterioration
of cellular functions, becoming targets of reactions, which can lead to increased
ROS generation, mutations, oxidation of mitochondrial proteins, and more.
Keeping healthy mitochondrial activity and biogenesis capacity during aging is a
key factor in preventing the progression of age-related diseases that affect the
tissues and organs.

14. REFERENCES
1- Schardt, D. (2008). Manipulating mitochondria. Nutrition Action Healthletter, 35(10),
8-10.
2- Friedman, Jr. & Nunnari, J. (2014). Mitochondrial form and function. Nature, 505, 335-
343.
3- Baker, M.J., Frazier, A.E., Gulbis, J.M., & Ryan, M.T. (2007). Mitochondrial protein-
import machinery: correlating structure with function. Trends Cell Biol, 17, 456-464.
4- Iyer, S.S., He, Q., Janczy, J.R., et al. (2013). Mitochondrial cardiolipin is required for
Nlrp3 inflammasome activation. Immunity, 39, 311-323.
5- Rockstein, M. & Brandt, K.F. (1963). Enzyme changes in flight muscle correlated with
aging and flight ability in the male housefly. Science, 139, 1049-1051.
6- Franceschi, C., et al. (2007). Inflammaging and anti-inflammaging: a systemic
perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev,
128(1), 92-105.

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