[Music]
hi I'm Amy proall I'm the president and
research director of poly bio Research
Foundation and today I'm truly excited
to talk to you about viruses and chronic
aging building a research community so
where am I going with this first what I
want to talk about is viruses as drivers
of Aging processes this is really not
discussed and as understood as it should
be and there's so many compelling
examples of how viruses can contribute
to Chronic aging processes this is
really important for the longevity
community and for people who are just
dealing with many forms of chronic
disease if we understand these
interactions we can better figure out
how to combat them and how to best uh
create strategies to mitigate uh viral
effects on Aging so let me give you some
examples of viruses and how they
contribute to aging process
so there's definitely many drivers of
human aging but here are some of the
three main factors mitochondrial
dysfunction these are the Just Energy
powerhouses of ourselves and they become
dysfunctional as we age often
inflammaging which is basically just the
fact that over time as people get older
tend to have more chronic inflammation
more immune cells that are just
activated in an unproductive way that's
called inflam Aging and cognitive
decline obviously people who are getting
older and aging have memory problems
they have brain you know dementia even
post Alzheimer's type phenomenon even
sometimes so one thing to understand is
that as we age and in fact as we are
born um and across the Scopes of Our
Lives we inherit um viruses from our
parents chronic viruses sometimes um
they passed in some cases in the womb
plus we also over the course of our
lives and this happens with exposures
with other people it happens from our
environment and sometimes the foods and
other things that we consume we
accumulate different viruses and they
become part of what is known as our
human viral the viruses in us and there
are many viruses that become a burden in
our systems as we just live these are
the herpes viruses the papiloma viruses
um and increasingly a growing number of
RNA viruses are also understood to be um
persistent viruses that are with us for
our life now what does this virum then
do to aging well consider are just some
of these virum components this is you
know sometimes when people are let's say
in college they gave mono and people
understand that people get sick they get
a sore throat they don't feel well
they're feverish they try to avoid
people for a while what really means uh
when you get mono is that you get the
abstain bar virus it's a herpes virus
and that virus stays with you again this
is a persistent virus once you have it
it does not clear your system it stays
with you for the rest of your life this
is the thing if someone's immune system
is robust if it's in a good shape if
it's active what the immune system does
technically is keep these chronic
viruses like the Epstein bar virus if
you get it and over 90% of people in the
world by the way Harbor Epstein bar
virus keeps these viruses in check it
keeps them in a dormant form the immune
system keeps them in a latent form and
that way they technically cannot
activate and create more proteins or
things that can actually drive disease
or potentially aging
processes
now however if viruses do become active
if they are moving out of a state of
dormy because something happens to the
immune system and this could be many
things it could be another infection it
could be just exposure to pollutants to
chemicals to many things that wear down
our immune systems over time viruses can
become more active and one of the things
that viruses do when they activate is
that they affect our mitochondria
directly in fact this is one of the key
things to understand about viruses our
health and aging is that viruses are
actually obligate intracellular
pathogens and what that means is by
definition they are not even alive they
must in order to replicate and create
new versions of their cell they must
pull the substrates the backbones to do
that to create new versions of
themselves from our human cells from our
mitochondria so they do this every
single virus hijacks our mitochondria in
order to create new versions of itself
and do basically anything that it does
this is a paper that I wrote about this
phenomenon with my colleague
neuroscientist at Poly bio Mike Van oer
who also is a neuroscientist at Harvard
we wrote about how pathogens bacterial
viral fungal parasite pathogens even
hijack the metabolism or the
mitochondria of the host cells they in
fact to just gain those basic substrates
again to just create new versions of
themselves this is core to what they do
this is a diagram from our paper this is
basically a human mitochondria in the
diagram at the intermediate of that
paper of the figure you can see the TCA
cycle that's a very important part of
just gaining substrates for our own
energy metabolism so that we can
function burn glucose you know burn
other fuels that allow our mitochondria
to make us a energy producers in a in a
good way the blue boxes contain
different human viruses that are part or
can be part part of the human virum
persistent chronic viruses and those are
just the different parts of metabolic
pathways that they hack or hijack as
part of their ability to just create new
versions of themselves or replicate okay
so I mentioned before that inflammaging
just chronic inflammation often
accelerating over time is also strongly
associated with human aging and issues
with longevity for example in this paper
now what inflammation often results from
is the activation of immune cells
including cyto which become active and
question one of the questions is why but
we certainly know that especially cyto
amans cells become active now I 11 is an
example of a cyto so it's an
inflammatory molecule in the human body
that can become more active When Things
become inflamed now this doesn't make
you know seem too surprising then in
this paper this team showed that
inhibiting this INF inflammatory
molecule the cyto uh I 11 extended Mamon
Health span lifespan suggesting that
inhibition of some forms of inflammation
is helpful for in that regard now what
though in the first place was causing
that cygine I 11 or interlan 11 to be
active to be more active than it should
be well one of the biggest driving
factors again that so many viruses and
other bacteria or pathogens or parasites
do is they activate immune cells as part
of their persistence what happens is the
immune system recognizes them tries to
Target them or to keep them in check and
in the process becomes more active
perpetually more perpetually active so
here is a study showing that that cyto
um il1 or Incan 11 is actually
stimulated both in animals and in the
lab by viruses including respiratory
viruses so these are drivers of
inflammaging most pathogens can be
direct drivers of
inflammaging okay now we just have the
ability the viruses and bacteria but I'm
going to focus on and viruses here can
basically just hack the signaling
Pathways that are the heart of our
longevity health networks for example
there are Pathways in the human body
that control processes associated with
cellular inessence for example that's
the ability of a cell to correctly
divide to correctly grow not overdo that
not sort of underdo that process but to
do it
robustly there are networks in the human
body that scientists have calculated as
mattering in terms of human signaling
associated with longevity well this team
did network-based analysis and they
uncovered dozens of viruses that encode
proteins experimentally demonstrated to
interact with proteins associated with
these human aging networks including
cence so so just dozens of viruses and
and thousands of interactions between
these viral proteins to the point where
they ended up calling dozens of viruses
in the study that they identified age
disorders because of the fact that their
proteins could have such detrimental or
modulator effects on these aging
networks in other words their
reproduction and their ability to
replicate benefits from directly from
interference with their host aging
processes and here on this chart are
just some of the top viruses that were
basically shown to have proteins that
interfered with human cellular inessence
Pathways there are the herpes viruses
which most of us acquire over the course
of Our Lives the papiloma viruses
interestingly influenza A virus was one
of the top drivers of aging and we never
even think about the flu type viruses
which is influenza in an aging capacity
um but we probably should a little bit
more so with that in mind
then this is a final takea away from
that paper this is what the team
concluded owing to the considerable
number of human viruses this
evolutionary minded view encourages a
reconceptualization of the Locust of
Aging no longer exclusively focused on
our own genetic material but expanded
towards a larger set of genetic entities
interacting with our species such as
viruses so Boom the heart of Aging all
right now what about cognitive decline
what about just direct mechanisms by
which viruses or other pathogens can
drive cognitive decline here is one this
is the team that we work with at Harvard
Medical School they're really cool
they've been using models of a brain in
a dish where they actually recreate the
neuron structures of a brain in a model
or just experiments in mice to show that
the Alzheimer's plaque the ameloid beta
plaque that is the the Flack that forms
in the brains of patients with
Alzheimer's disease that defines the
disease actually acts as an
antimicrobial peptide or part of the
immune response that forms in response
to pathogens directly in order to combat
them so basically what happens is
there's a virus that gets into the brain
tissue model and then the plaque forms
around it as part of the response to the
virus that's what they were showing in
this study in response to the herpes
viruses but the te is also sewn the same
Phenomenon with bacterial pathogens and
with fungal pathogens this places
infection at the heart of the driving of
amalo plaque in the Alzheimer's brain
here's another example of a team who's
working on the same phenomenon Ben re
heads group at Arizona State University
this is an image of cytomegalo virus
which is another herpes viruses that
many of us just carry with us for life
it's look in the image here it's
concentrated in the micral immune cells
of the brain around the plaques of these
cells along with the axin and dendroides
of neurons again that are inflamed and
directly part of the Alzheimer's disease
process so there are growing number of
teams connecting viruses directly to to
neurod
degeneration now this is an interesting
study okay what do we do well there's
some really low hanging fruit no one's
even doing anything about this and this
is an example of just easy measures we
could take to control the impact of
viruses on Aging if we made it a
priority this is the team in Taiwan and
what they did is they tracked people
over time some of whom were given just
aordable herpes virus existing generic
medications so for example let's say
someone gives genital herpes they're
given Val checks it's just an
over-the-counter herpes anti- herpes
virus drug so some of the people in the
study were given more of those anti-
herpes virus drugs and some weren't when
they looked at the group that was given
these anti-herpetic medications they had
a much lower risk of dementia than the
people who didn't in fact up to a 10
times lower risk of dementia so really
it's extremely low hanging fruit to
maybe start to use some of the drugs
that we have to inhibit viral activity
in the context of human
aging now what about in covid Long covid
now I know we're all a little burned out
on covid but really like part of what
our group does is studies still The
Chronic consequences of SARS Co 2 we
have to it's because it's one more virus
that is one of these players that could
contribute to chronic disease and
fortunately aging processes and you'll
hear about long Co and it sounds like a
vague phenomenon when you hear about it
in the news often really it's not though
a lot of us that are directly studying
long covid realize that the Persistence
of the SARS Co 2 virus in tissue in the
human body over time in other words SARS
code 2 potentially becoming just another
member of the human viron is happening
in at least a decent number of people
with long covid and here's a paper that
a group of us of long Co researchers
wrote about SARS Co to persistence as a
driver of postco symptoms here's an
example of a team that we work with this
is in the bottom right gut tissue from
the lining of the gut collected from
someone almost in one case over two
years after they got covid and in this
case the person did have symptoms they
had chronic symptoms but still this that
what you're seeing there in the purple
that that pink part is the SARS cooku
virus still there in the gut tissue
after over two years sort of embedded
there with immune cells around it
clustered preventing it potentially from
being cleared so it's there in a
persistent capacity which means that at
least in some people SARS cve 2 may be
acting or seems to be acting as a
persistent virus that can also
contribute to chronic disease and aging
processes in fact this is a table from
one of our papers that just this is just
some there are some of the studies that
have shown persistent SARS cope 2 up to
again then over two years or more after
initial infection and at least a sub set
of people okay so then what do we do
about this well one of the drugs we're
actually looking about in the long covid
world is rap ayin which I know that some
of you will be familiar with in the
context of mitigating aging or or
extending life span so we are actually
running at Mount Sinai um in New York
where I serve as the scientific director
of a clinic called core um which is a
treating people with conditions
initiated or exacerbated by infection is
we're running a trial of Romy in
patients with long covid rapamycin is an
mour inhibitor that has you know
different properties on the immune
system now one of the things that's
really interesting about Ramy is that in
some studies at least rapalogues or
analoges of vamy and drugs similar to it
have been shown to in a low once a week
dose not in a high dose in a lower dose
to enhance parts of the immune response
that can better control viral infection
so for example that TR that I showed you
gave patients two rapalogs over the
course of six weeks and a couple things
happened first they showed the people
taking Romy and an increase and
interferon induced antiviral gene
expression with interferons being one of
the primary molecules or parts of the
human response that combats viruses and
keeps them down also the people in rap
the ramyon group everyone in the trial
was given the influenza vaccine but
those who took Ramy had a more robust
response to the vaccine in other words
their immune system seem to activate
more and create more antibodies in
response to that vaccine also the
participants on Ramy even though they
just took the drugs for six weeks
reported a lower rate of infection for a
full year after being on the rapy this
includes respiratory infections UTI
though all a multiple types of infection
suggesting again that rapamycin was
helping to control viral activity and in
a related study the team found that
rapamycin in some patients um improved
t- cell exhaustion and again when
viruses persist they tend to knock down
te- cells uh and their activity which
are parts of our immune system making
them literally exhausted and rapamycin
was shown to potentially improve that
again so rap ayin we're triing now to
see if it might help patients who have a
persistent SARS C2 or other virus
problems in Long covid better control
those infections and with this means is
there's you know a use of Romy in terms
of potential viral control that is also
probably relevant to human aging