Mitochondria & Aging | Modern Healthspan Clips
Summary
TLDRThis video discusses the critical role of mitochondria in cellular health and aging. Mitochondria, often referred to as the 'powerhouses' of the cell, are essential for energy production and participate in numerous cellular processes. As we age, mitochondrial dysfunction is linked to neurodegeneration, making early detection crucial. The video delves into the complexity of mitochondria, their genetic uniqueness, and their heterogeneity across different tissues. It also explores the concept of mitophagy, a process that removes damaged mitochondria, and the importance of maintaining mitochondrial health through interventions like exercise and supplementation with magnesium. The discussion highlights the potential of mitochondrial microproteins in treating age-related diseases and the ongoing research in this field.
Takeaways
- 🧬 Mitochondria are essential cellular organelles with numerous functions, including energy production and participation in various cellular processes.
- 📉 With aging, there is a loss of mitochondria and a decline in their function, which is an early indicator of neurodegeneration.
- 🔬 Mitochondria are heterogeneous, with different sizes, functions, and genetic backgrounds, making their study complex.
- 🧬 Mitochondria contain their own genome, separate from the nuclear genome, which is simpler and contains genes for energy production and other functions.
- 📊 Aging affects mitochondrial function, leading to changes in energy production and structure, which can be measured through various clinical methods.
- 🧐 Mitophagy is a process that removes damaged mitochondria and is crucial for maintaining cellular health and preventing neurodegeneration.
- 💊 The peptide humanin, encoded in mitochondrial DNA, has been shown to have beneficial effects on aging and cognitive decline.
- 🔍 Scientists are discovering many small open reading frames in mitochondrial DNA that can encode microproteins with potential roles in aging and disease.
- 🏋️♂️ Exercise can stimulate the production of beneficial mitochondrial microproteins, such as Moi, which has potential roles in weight loss and muscle health.
- 💡 Magnesium is crucial for cellular function and supports optimal mitochondrial function, potentially reducing oxidative stress and cellular aging.
- 🧪 Mitochondria from different tissues have distinct functions and produce different peptides, indicating the importance of context-specific mitochondrial health.
Q & A
What are mitochondria and why are they important for our health?
-Mitochondria are small organelles found in the cytoplasm of cells, with multitudes per cell. They have many functions, including energy production in the cell, which is one of their most important roles. They also participate in numerous other processes and interact with the cellular environment and nuclear processes. Mitochondria are crucial for health as they play significant roles in aging and are targeted for their dysfunction as an early indicator of neurodegeneration.
How do mitochondria change as we age?
-With aging, there is a loss of mitochondria and a loss of function in them. Energy production can decrease or become dysfunctional. The structure of mitochondria changes, and their organization within the cell is also altered. These changes are observed early in neurodegeneration and other diseases.
How can we measure mitochondrial function?
-Mitochondrial function can be measured directly with energy production measurements using sophisticated equipment. Additionally, electron microscopy can be used to observe the structure and organization of mitochondria, including how many there are and their size variations.
What is mitophagy and how does it help with mitochondrial health?
-Mitophagy is a targeted process of autophagy that gets rid of bad or dysfunctional mitochondria. It helps maintain overall mitochondrial function by ensuring that only healthy mitochondria remain in the cell, which is crucial in preventing the accumulation of dysfunctional mitochondria that can cause problems in the cell.
How do mitochondria regenerate themselves?
-Mitochondria can be disposed of and new ones generated through a process that involves both fission, where mitochondria divide, and fusion, where they merge to form a network. This dynamic process helps maintain a healthy population of mitochondria within cells.
What is the significance of mitochondrial DNA and how does it differ from nuclear DNA?
-Mitochondrial DNA is a small, circular genome with only a few genes that code for mitochondrial energy function. It differs from nuclear DNA, which has a large genome with thousands of genes and a complex structure. Mitochondrial DNA is also unique because it is inherited maternally, unlike nuclear DNA.
What is the role of microproteins encoded by mitochondrial DNA?
-Microproteins encoded by mitochondrial DNA, such as humanin, have been found to have various beneficial effects on health, including protecting the brain from cognitive decline, delaying aging processes, and preventing diseases like Alzheimer's and diabetes. They are considered important in aging due to their role in repairing and correcting biological processes.
How does the mitochondrial peptide humanin impact health and aging?
-Humanin is a novel small peptide encoded in mitochondrial DNA that, when secreted and circulated in the body, has been shown to protect against cognitive decline, fibrosis, and atherosclerosis. It is considered a quintessential mitochondrial peptide with significant roles in aging and disease prevention.
What is the potential role of magnesium in supporting mitochondrial function?
-Magnesium is a critical mineral for cellular function, particularly as it is bound to ATP, the cellular energy currency. Magnesium deficiency may contribute to oxidative stress, accelerated cellular aging, and mitochondrial dysfunction. Supplementing with magnesium, such as through Magnesium Breakthrough, can support optimal mitochondrial function.
Do mitochondria from different tissues function differently?
-Yes, mitochondria from different tissues like brain, liver, and muscle are very different. They have distinct energetic profiles, proteomic distributions, and functions, which can be influenced by disease states and interventions.
How does the process of mitophagy decline with age and impact mitochondrial health?
-As we age, the efficiency of mitophagy declines, leading to an accumulation of dysfunctional mitochondria that cannot be removed as effectively. This results in increased oxidative stress and reduced energy generation, contributing to cellular aging and the development of age-related diseases.
Outlines
🧬 Mitochondria's Role in Aging and Health
The video script begins by discussing mitochondria, the cell's energy-producing organelles, and their importance to health. It explains that mitochondria are not only vital for energy production but also participate in numerous other cellular processes. As people age, there is a decline in both the number and function of mitochondria, which is linked to neurodegenerative diseases like Alzheimer's. The speaker expresses interest in targeting mitochondrial dysfunction as an early sign of such diseases. Various methods to measure mitochondrial function are discussed, including energy production measurements and electron microscopy to observe mitochondrial structure. The script also touches on the genetic aspects of mitochondria, which are inherited maternally and have a simpler genome compared to the nuclear genome.
🧬 Mitochondrial Changes and Mitophagy
This paragraph delves into the complexities of mitochondrial aging and the concept of mitophagy. Mitochondria are heterogeneous, with different sizes and functions, and their genetic material is matrilineal. The script explains how mitochondria can regenerate and be disposed of, but as they age, they can't generate new ones that are younger. The process of mitophagy, which is the targeted destruction of damaged mitochondria, is highlighted as crucial for maintaining cellular health. The importance of effective mitophagy in preventing the accumulation of dysfunctional mitochondria and its role in diseases like neurodegeneration is emphasized. The unique features of mitochondria, such as their own chromosome and the discovery of additional genes within mitochondrial DNA, are also discussed.
🧬 Mitochondrial Peptides and Their Impact on Aging
The script introduces the concept of mitochondrial peptides, small proteins encoded within the mitochondrial DNA that have significant biological roles. One such peptide, humanin, is highlighted for its protective effects against cognitive decline and other aging-related issues. The discovery of numerous small open reading frames within mitochondrial DNA, which could potentially translate into hundreds of microproteins, is discussed. The importance of these microproteins in aging is underscored, as their production decreases with age, potentially leading to diseases like diabetes and Alzheimer's. The script also mentions other mitochondrial peptides, such as SCHLAP2 and MOI, which show promise in combating aging and related conditions.
🧬 Tissue-Specific Mitochondrial Function and Peptides
This section of the script emphasizes the variability of mitochondria across different tissues. It explains that mitochondria from brain, liver, and muscle are distinct in their appearance, proteomic profiles, and energetic functions. The development of a technique akin to RNA sequencing, but for analyzing mitochondrial peptides, reveals that the expression of these peptides varies significantly from tissue to tissue and is sensitive to disease states and interventions. The script suggests that understanding these tissue-specific mitochondrial peptides could be key to addressing various diseases and conditions associated with aging.
🧬 Mitochondrial Dynamics and Aging
The script discusses the dynamic nature of mitochondria, which are constantly generated and replaced to maintain cellular homeostasis. It explains the processes of mitochondrial biogenesis and mitophagy, which are crucial for clearing damaged mitochondria. The importance of mitochondrial dynamics, such as the fragmentation and networking of mitochondria, is highlighted in relation to metabolic efficiency and the ability to be cleared by mitophagy. As aging occurs, the script notes a decline in these processes, leading to the accumulation of dysfunctional mitochondria, increased oxidative stress, and a decrease in energy generation, which can contribute to cellular damage and disease.
🧬 Encouraging Mitophagy and Mitochondrial Health
The final paragraph explores ways to stimulate mitophagy to combat the decline in mitochondrial function associated with aging. It mentions genetic pathways that modulate mitophagy and the role of nutrient sensing in this process. The script also discusses the potential of pharmacological interventions, such as the use of ursolic acid, to promote mitophagy in tissues like the brain and muscle. The importance of maintaining mitochondrial homeostasis for overall health is reiterated, along with the potential benefits of supplements like magnesium for supporting optimal mitochondrial function.
Mindmap
Keywords
💡mitochondria
💡aging
💡mitochondrial dysfunction
💡mitophagy
💡neurodegeneration
💡microproteins
💡humanin
💡Moi
💡mitochondrial DNA
💡magnesium
Highlights
Mitochondria are essential for health, with functions beyond just energy production.
Mitochondrial dysfunction is an early indicator of neurodegeneration.
Mitochondria are heterogeneous, with different sizes and functions even within the same cell.
Mitochondrial genetics are matrilineal, with a simple genome distinct from the nuclear genome.
Aging is associated with a loss of mitochondria and a decline in their function.
Mitochondrial function can be measured directly with energy production measurements and electron microscopy.
Mitochondria regenerate themselves through processes of fusion and fission.
Mitophagy is a process that rids the cell of dysfunctional mitochondria, which is crucial for cellular health.
Mitochondrial DNA is more prone to damage, and its function declines more rapidly than nuclear function.
Mitochondria contain their own chromosome and can produce proteins within the mitochondria.
Humanin is a peptide encoded in mitochondrial DNA with beneficial effects on aging and cognitive decline.
Mitochondrial DNA contains many small open reading frames that can be translated into microproteins.
Microproteins from the mitochondria are believed to play a significant role in aging.
Schlep2 is a microprotein showing promise in translating into treatments for human diseases.
Moi is a microprotein with exercise-mimetic properties that could treat conditions like obesity and frailty.
Magnesium is crucial for cellular function, particularly in supporting mitochondrial function.
Mitochondria from different tissues have different functions and produce different peptides.
Mitochondrial DNA damage accumulates over a lifespan, but less functional mitochondria are eliminated through mitophagy.
Mitochondrial function and dynamics are essential for maintaining cellular homeostasis and adapting to metabolic needs.
As we age, the balance of mitochondrial function declines, leading to the accumulation of dysfunctional mitochondria.
Mitophagy can be encouraged through genetic pathways and pharmacological interventions, such as with ursolic acid.
Transcripts
[Music]
so what I'd like to talk about is
mitochondria and particularly how they
impact us as we get older but kind of
starting at the beginning kind of very
briefly what are mitochondria and why
are they so important to our
health yeah mitochondria are our little
organel we have in the cell multitudes
per cell of these small organ Els and
they have many
functions for for a long time people
thought they were just making energy in
the cell and that's one of their most
important functions but they also are
participate in multitudes of other
processes in the cell interact with the
environment in the cell with the nuclear
processes so the mitochondria are not
part of what we call the nucleus of the
cell they are around the nucleus they're
in a cytoplasm
of the cell but they play enormous
amounts of of uh important uh roles in
processes also in aging and so with
aging we know that there is a loss of
mitochondria there's also a loss of
function in the
mitochondria and uh we have begun to
Target mitochondrial dysfunction as a
very early indicator of neurod
degeneration so that is one of the
things that really attracts my interest
is that it seems to be one of the
earliest things that happen in the cell
is some changes with mitochondrial
function that then leads are the early
steps probably in Alzheimer's and other
neur
degenerations so it's very important to
understand these
changes at the earliest possible
stage so how do you how do you tell that
the mighty is is there any kind of
clinical way of telling your
mitochondria are not functioning
correctly yeah there are there are a
number of different ways and and
mitochondria by the way are very
heterogeneous we have different kinds of
mitochondria different sizes of
mitochondria different functions of
mitoch condia even within the same cell
so it makes it quite
complicated and then they are the
genetics rely on the the female rather
than the male as is well known and so
the whole organization in genetics and
and of mitochondria is is very
intriguing and while in the nucleus we
have a large genome with 20,000 genes
and very complex structure and
organization The genome that is found
inside the mitochondria is a very simple
small plasm or circular DNA with only
few genes that code for mitochondrial
energy function and and other proteins
other functions that are being brought
into the mitochondria are coded for by
the nuclear DNA so we have two different
genomes within one cell it can be the
mitochondrial genome and the nuclear
genome so how do how do mitochondria
change as they get old as we get old so
so we talk about the dysfunction in what
way are they
dysfunctioning yes so I you also
mentioned how do the how do we measure
mitochondria so
we can measure mondro function directly
with energy Pro measurements and in in
in in sophisticated equipment and we can
also look at the mitochondria with
electron microscopy and look at the
structure of the mitochondria
organization of mitochondria how many
mitochondria there are and other such
things so what's been observed is that
there are a number of things that go
wrong with mitochondria with aging
energy production can change usually go
down but can also be activated so it
gets
dysfunctional it gets out of wacko with
age in the mitochondri energy production
and then there are other processes the
mitochondria we can also observe the
structure of the mitochondria
changes the uh Fusion fish we call it
between how mitochondria organized
themselves is also changed so there are
a number of processes that change with
aging and also early on reur De
generation for example and other
diseases yeah I wanted to talk about the
disease but but one thought you know so
mitochondria they they generate
regenerate themselves right uh they
separate fusion and fish yeah and
fishion uh I mean if they're generating
new ones why are the new ones kind of
older can't they generate new ones which
are
younger yeah yeah it's a it's a it's an
interesting question yeah they they
could in a way but they really can't so
it depends on on a number of things also
the genetic background mitochondria and
and and many processes but they they you
have a we have a heterogeneous
population of mitochondria so they can
be mitochondria at different should we
say stages and ages within one
cell and and and makes it makes it it
complicated but mitochondria can also be
disposed of and new mitochondria
generated all the
time so I was gonna ask about that so so
mitophagy and the getting rid of the
existing mitochondria which seems to be
a way of helping with their health like
how does mitophagy help with the overall
function of
so
mitochondria get bad with aging and
neuro
degeneration neuro degeneration as we
just talked about in in different ways
and the process of replacing these
mitochondria getting rid of the bad ones
is the mitophagy process so we have a a
general process called autophagy in the
cells getting rid of cells more General
ways and then we have a targeted one
that gets rid of the bad mitochondria
and you can
actually tell that mitochondria are bad
if you will or dysfunctional in in for
example electron microscopy where the
structure looks um abnormal and it just
simply uh so they need to be disposed of
if we don't get rid of those bad
mitochondria they accumulate they they M
they they fill up and take and and
simply cause various problems in the
cell the bad mitochondria so we we
really need to have an effective process
of replacing the bad mitochondria and
that is done
by a special organization involving
lomes and and acidic milu in the cell
that then degenerates the mitochondria
that not
functional let me start with the
mitochondria so our body is made of
cells all cells except perhaps red blood
cells contain
mitochondria mitochondria have multiple
roles they are the energy source of the
cells uh they also have uh function as
immune Regulators as metabolic
Regulators as inducers of programmed
cell death and mondal dysfunction is
involved in many different diseases but
particularly in diseases of aging and
everything we said about age in general
applies to the mitochondria and Spades
mitochondria are much more prone to uh
DNA damage they uh their function
declines much more rapidly than nuclear
function and they accumulate neurom
mutations and uh uh see damage as we age
the one thing that makes the
mitochondria unique is it contains its
own
chromosome this chromosome is much
smaller than the nuclear chromosomes
it's only 16,000 base Bears which isn't
much and it contains 13 large protein
coding genes that are part of the
so-call respiratory chain that allows
the mondria to uh turn oxygen into
ATP and also has its own ribosome system
that allows it to produce proteins
Within theond Anda that was the thinking
up till 20 years ago when we and a
couple of other groups stumbled on an
observation that there is a small Gene
within a gene in the mitochondrial DNA
that uh a scientist who has already
passed away from Tokyo Japan named
nishimoto he named that prodin humanin
my lab cloned it at the same time that
he cloned humanin was the first to
recognize its importance and publish it
um we became friends in the early 2000s
and appropri fortunately he died from
cancer uh a little over 10 years ago
um humanin turned out to be this novel
small peptide encoded in mondal DNA we
believe it get uh the MRNA for human in
goes from the mitochondria to the Cy
plasm where it gets translated into this
little peptide 24 amino acid peptide
gets secreted out of the
cell and then circulates around the body
and has really tremendous beneficial
effects from protecting the brain from
cognitive decline from protecting aging
tissues from fibrosis and other damage
uh from delaying or preventing
atherosclerosis and and there are now
probably over 500 Publications from over
30 Laboratories around the world
demonstrated the various beneficial
effects of humanin in animal models
mainly mice and rats in in uh primarily
the context of
aging and so humanin is sort of the
quintessential mitochondrial peptide so
about 17 years ago 15 years ago uh in
one of our lab
meetings we started asking if there is
one small open reading frame hiding
inside a larger Gene why shouldn't there
be more of them and we started studying
the mitochondrial DNA looking for
additional open reading frames and by
now we realized that there are many
hundreds of them probably six or 7
hundred small open reading frames
Each of which can be conceptually
translated into a small peptide uh by
the way these days we like to call them
microproteins rather than micropeptides
that's the latest Trend and many many
hundreds of microproteins can
theoretically be made by the
mitochondrial
DNA we have now uh believe that we
identify dozens of these in the
mitochondria and the big change that
that happened in the field is that
people have started recognizing that
their microproteins these small open
reading frames that get translated
translated into peptides they exist also
in the nuclear
genome and there are actually hundreds
of thousands if not millions of small
open reading frames that can encode
microproteins in the nuclear genomes and
there are multiple groups working on
these in fact there was this really
interesting family of molecules known as
long n coding rnas that was discovered
about 15 to 20 years ago and by their
name it implies that they don't code for
any
protein now people are recognizing that
many of these long L coding rnas
actually do code for
microprotein so the science of
microproteins is
expanding we like to believe that we
started it and that we really are moving
the needle in the mitochondrial sphere
but many outstanding scientists are now
working on uh nuclearly encoded m u uh
microproteins that have important
biological roles I happen to believe
that these microproteins from the
mitochondria from the mitochondrial DNA
that we work on are particularly
important in aging precisely because
during the aging process there is so
much
damage to mitochondria and mitochondrial
DNA that the production of these
mitochondrial microproteins goes down
leading to uh poor performance of
certain things certain tissues certain
biological processes and resulting in
diseases like diabetes and Alzheimer's
disease and other diseases like fibrosis
which mitochondrial microproteins can uh
repair correct and
reverse so uh when we recognize that
there could be more mitochondrial
microproteins we started out initially
by just saying okay here's
humanin right next to it there's another
open reading frame let's see what that
one does and we named a bunch of them
small human like peptides or
schleps one of them is called schlep 2
and it's a very exciting microprotein
that we're working on been published now
in about 10 or 15 papers and to me it's
one of the most promising candidates
that can be translated into human
disease and whether that disease would
be Parkinson or some other condition
we're still unraveling but about a
decade ago and we published this in
2015 we noted that there was a small
open reading frame a little bit further
away from humanin which we called
Moi and Moi turned out to be a
fascinating
microprotein and it has uh exercise
mimetic and exercise enhancing
biological activity that result in
weight loss in my our obese or for high
fat diet um reduction in steatosis
or apotosis is fatty liver one of my
colleagues is not showing that it also
decreased something called myosteatosis
which is a really underappreciated
severe process of Aging where there's
fat accumulation in muscle and Mai uh
amarate that and reverses that so Mai
which is also regulated by exercise if
you exercise you secrete matsi uh is an
exciting peptide with potential roles in
a number of conditions from Frailty to
obesity to fatty liver and we licensed
this to the company uh Cobar that near
barcel I and myself founded a little
over a decade ago and it has completed
phase one studies and is now planning uh
phase two studies with Mai as well as um
identifying several other potential
important microproteins from the
mitochondria which uh they will
hopefully develop for additional
diseases of Aging such as uh idiopathic
pulmonary fibrosis and related condition
do you know magnesium is a critical
mineral for cellular function perhaps
the most important role is being bound
to ATP the currency of cellular energy
as magnesium ATP complex which is the
recognized form of the co-actor required
for proper function by hundreds of
enzymes research suggests that magnesium
deficiency can contribute to increased
oxidative stress accelerated cellular
aging and mitochondrial
dysfunction to make sure that we are not
deficient and to support optimal
mitochondrial function my wife and I
take magnesium breakthrough daily unlike
some supplements offering limited forms
magnesium breakthrough is made of all
natural ingredients and contains full
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support do the mitochondria and the
different tissues
produce are they different I mean do
they work in different ways and do they
produce different
peptides absolutely and I think it's not
really appreciated even by many
scientists that the mitochondria from
say brain and liver and muscle are very
very different they look different by
electron microscopy if you isolate
mitochondria and do a proteomic analysis
you see very different distribution of
uh proteomic uh uh results if you look
at the function they're quite different
in their energetic profile so uh it's no
surprise that we identify different
profiles of expression of mitochondrial
peptides one of the techniques that
we've recently developed is the
mitochondrial equivalent of what's known
as RNA seek RNA seek is a technique that
was developed to measure the RNA from
tissue samples and look at all the
20,000 genes that Express RNA and
eventually proteins and see what goes up
and what goes down in various
conditions the standard RNA seek does
not look at microproteins certainly not
in the mitochondria and we've developed
a method to specifically analyze the
expression of mitochondrial peptide that
the RNA level and they're very different
from tissue to tissue and it's very
sensitive to uh disease States and
interventions of all sorts and um indeed
uh uh the profile of mitochondrial
peptide that are produced by
mitochondria from different tissue is
very
different interesting yeah I because I
always sort of mitochondria is being the
same like everywhere kind of like
standard issue you stick them in cells
and they just make energy but it's not
the
case that's interesting
yes there's a concept of mitochondria
transplant right so you can take
mitochondria and put them into uh
tissues and you know taking them from
one type of tissue to another can have
profound effects it's still a concept
that is in development and it's not
quite ready for you know even clinical
trials but um which mondria you start
with is going to have a major effect on
the results you're going to
get one question on mitochondria and
aging so do does the DNA damage in a
mitochondria just accumulate and
accumulate like over our whole a our
whole lifespan or do they have like I
don't know can they reset right so the
mitochondri employ a very different
model than normal Maman cells they are
essentially continue to function the way
unicellular bacterial like organism do
they divide much more first of all a
cell has two chromosomes uh two sets of
chromosomes and one cell and the cell
divides as needed in the tissue but each
cell has hundreds potentially thousands
of
mitochondria and the mitochondria divide
in an
asynchronous fashion with the rest of
the
cell and um there are many mitochondria
and they undergo a process known as
mitophagy which is kind of like
autophagy where a whole cell gets sort
of
eliminated uh when it it's done with its
role poorly functioning or sort of not
quite uh 100% effective mitochondria
gets eliminated through the concept of
mitophagy and even though we said that
there's a lot of damage that uh happens
to mitochondria as you age a lot of
these less than perfect mitochondria get
eliminated through this mitophagy
process
so you're always going to have some
functioning mitochondria but if you're
you know 18 your body is really good at
getting rid of all the abnormal
mitochondria and keeping like a really
good cohort of fully functioning
mitochondria but a time you reach my age
you know there are more and more of
these sort of semif functional ones that
are trying to do the job uh by the time
you get to 100 there's even less quality
control there um and you know that that
happens at a steeper rate than some
other uh components of the cell all of
which age but mondria seem to age
fastest among the different uh elements
in the
body how do the mitochondria change with
age and kind of what are the driving
factors
but push them so yeah so again it's it's
a it's a complex matter I mean in sense
that mitochondria very complex and
dynamic organ and and and they let's say
what happens normally the way that they
maintain ostasis is that they are
constantly generated and replaced
essentially um depending on the stimuli
and the uh metabolic inputs that I get
and the needs of the cells so and again
as I mentioned also before the way to
Main mitochondri mesis is either through
generating new mitochondria so
mitochondri bi bio biogenesis or
mitophagy in order to clear damage
mitochondria and also mitochondria
Dynamics are very important for this
because essentially mitochondria are can
be either fragmented and become like
more isolated and so on and this is when
they for instance can be taken up if
they are damaged to to be uh degraded by
mitophagy or they can be forming very
extensive networks to actually improve
or become more efficient in terms of
metabolic function so this normally
works uh very well and it's very Dynamic
and they can adapt very quickly in a
youthful or healthy status however over
time what happens is that due to the
decline also or in the other Pathways
that take care of things like
mitochondrial clearance uh loss of you
know let's say autophagy or other
Pathways that should be taken care of
reducing the damag mitochondria and the
fact that also mitochondria function in
terms of generation the energy so the
balance between the different complexes
within the mitochondria that would
generate ATP becomes altered due to
again um alteration of protein synthesis
uh reduced mitochondri biogenesis and so
on then the mitochondri start becoming
Also let's say less function in terms of
generating energy they may generate
perhaps more Ross and more oxidative
stress and they tend to accumulate also
so because they cannot be removed any
more efficiently through mitophagy
during aging due to the decline in this
process and so what happens is that you
tend to accumulate dysfunctional
mitochondria which then in term you know
they can start generating damage also
within the cells right because if you
have essentially more oxidative stress
and uh let's say less uh energy
generation and the inability to remove
this mitochondria essentially there will
be uh yeah that's when essentially
problems start occurring because then
you get an influence on the other all
marks as well so these all marks are
connected right so that's where it
becomes important to maintain om stasis
so how do we how do we encourage
mitophagy so uh yeah I mean from there
are several genetic uh Pathways that
modulate and mitophagy I mean in terms
of you know essentially that can be also
stimulated through let's say nutrient
sensing I mean there is uh the
involvement for instance of
phosphorilation processes that sense and
detect damaged mitochondria and then
they stimulate the ubiquity imp protome
system essentially uh to remove this
this so they attack the damage
mitochondria and then they recruit the
ubiquity imp protome system in order to
uh get rid of them pharmacologically
speaking there is I would say people are
actively looking to ways to specifically
Target mitophagy but I would say at the
moment perhaps one of the molecules that
I think it's very well known also in the
supplement space and so is tin a so that
one it's a natural molecule it's grass
recog oriz as generally U safe it's been
already used in humans a lot by um
essentially it's been discovered in my
ex Lab at epfl with the in the overx lab
and is now been used currently um um by
companies to do clinical trials and that
one seems to very strongly promote
mitophagy in several tissues and in
particular seems to work pretty well for
brain and muscle So preclinically
speaking with some initial evidence now
going for muscle aging in humans so that
one seems the most promising at the
moment yeah
[Music]
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