Cells and the Aging Process
Guest: Dr. Lina Obeid – General Internal
Host: Dr. Linda Austin –
Dr. Linda Austin: I’m Dr.
Linda Austin. I’m interviewing Dr. Lina
Obeid who is Professor of Medicine and, I understand, a couple other
departments as well.
Dr. Linda Obeid: Yes. I also have a secondary appointment in the
Department of Biochemistry and Molecular Biology.
Dr. Linda Austin: Dr.
Obeid, your research is in a very interesting area, the intersection of how
cells grow, which gets us into cancer, as well as into the aging process. You told me earlier that you have four
different grants going on now.
Scientists often think of their research in trying to answer a
question. If we’re to focus on one
aspect or one of those grants, what is the most interesting question to you
that you’re grappling with in your research?
Dr. Linda Obeid: A couple
of things. And maybe a good way of
putting it is the interface between cancer and aging. We know that cancer is primarily a disease of
aging, or significantly a disease of aging.
With age, your cells get more injury, more exposure to environmental
toxins or other injurious agents. And
they have a choice of becoming what we think of as cancer, that grow
indefinitely or mutate, or, if the normal process goes on, cells just become
old. What makes a cell decide to be what
we call a senescent cell versus what makes a cell decide to mutate into a
Some of the pathways that we study are at the cusp of that
decision. So, we try to tease out how
that happens. What are the targets of
some of these molecules that we study, and how do they make the decision to go
one way or the other?
Dr. Linda Austin: Now, at a
certain point in its life, does a cell have to make one decision or the
other? Is there a third choice?
Dr. Linda Obeid: Most
normal human cells are regenerating all the time and will regenerate from a
stem cell into a normal cell. Now, some
tissues regenerate more than others.
Some tissues cannot regenerate at all, for example, brain or neuronal
tissue cannot generate at all. But skin
tissue, gastroenteric tissue, for example, intestinal wall, these cells are
regenerating at a very fast pace. So, in
general, cells will want to differentiate into a normal cell. But if they see chronic injury from
environmental stresses or toxins, or genetic aberrations, there are a host of
underlying pathologies that would lead a cell to take one decision versus the
In general, the normal response would be for a cell, if it detects
something’s wrong, to undergo ptosis, or self-killing. A cell will undergo that under some injurious
circumstance or, potentially, could become cancerous and grow indefinitely if
it didn’t have these checks in place.
And in some cases cells cannot grow, cannot do either one of the
above. They just sit there and become
old. We call them senescent cells and
Now, this is a controversial question. Are there actually senescent cells and
tissues? We’re not sure. Aging may be sometimes more a fragility of
some cells such that they’re unable to regenerate as well, but they don’t have
to go on to become cancer. It’s not very
well understood whether, actually, our tissues have senescent cells or
not. It’s one thing we’re trying to
understand, aging versus cancer, versus normal processes. And that’s why stem cells become very
interesting, because they can become one or the other.
Dr. Linda Austin: If there
were one scientific question that you could answer in your career, write that
paper, do that research that answers that question, what would it be?
Dr. Lina Obeid: Cancer is
very important to me. I would really
like to understand what makes certain cancers.
Now, the thing about cancer, as you study it, you start to see that each
cancer is different. Not all cancers
have the same underlying pathology, but there are some common threads in
cancers. And those are deletions or aberrations
in certain genes that we know will lead to cancer. So, there are a few of these that are very
common among many cancers. For example,
mutations in a b53 pathway or mutations in the ras-oncogenic pathway will lead
So, these are some of the cancers I’m really interested in
finding, to understand these genetic mutations and to fix them. So, the pathway we work on is a lipid
pathway. Lipids form the cell
membranes. People thought they were just
the room that the cell lives in, or that some of the intracellular components
lived in. Lipids, fatty substances, are
impermeable to water so they hold compartments.
But some of the research we’ve done has led us to see that these
membranes also have a function whereby they’re metabolized in such a way that
they can send messages across cells, within cells and from cell to cell. And these lipids seem to mediate a lot of
underlying pathologies in cells, for example, something happens with DNA
damage, the lipids can detect that by some indirect mechanism and give a
signal. So, some of these things are
what I’m interested in solving and maybe preventing.
Dr. Linda Austin: So now,
in you lab, is this work done in tissue culture, in petri dishes? If I were to walk into your lab, what would I
Dr. Lina Obeid: It’s very
interesting. Even though I’m a
clinician, I started my career in very basic molecular studies and went into
more tissue culture models of disease.
And, now, we’re doing a lot of animal models. As the sciences progressed, we have been able
to identify the DNA of many genes, clone these genes and, with the advent of
the genomic sequence that has become available, we’re able to identify those
genes, pull them out, and now we can take mice embryonic cells and knock this
gene out and make a mouse model that lacks this gene. And if that mouse survives, we can study the
function of that gene. So, we’ve gone
from molecular to cellular to animal studies now. So, you can see all of the above in my lab.
Dr. Linda Austin: Dr.
Obeid, thank you so much for talking with us today.
Dr. Lina Obeid: Thank
you. It was a pleasure.
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