Turning up the volume on marin's happy, healthy lifestyle.
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turning up the volume on marin’s happy, healthy lifestyle.
Courtesy of the Buck Institute I. M. Pei–designed Buck Institute for Research on Aging 44 january/february 2021 marin living.
The Science
of Aging
Marin’s Buck Institute is one of the world’s enough exercise and enjoying quality
sleep, making it difficult to understand
foremost institutions for studying aging — and here which road to better health is the correct
we take a closer look at the life-changing science one (it’s actually different for everyone).
that is happening right in our own backyard. But the Buck’s goal is to shed some
BY CASEY GILLESPIE light on that as well. “In addition to our
research, this whole idea of (the Buck)
becoming a source of validated infor-
i
mation for the public, for me, is equally
N DECADES PAST, aging was left important,” adds Verdin.
to the old, but with new discoveries There is another piece of the aging
surrounding ketones and senescent science puzzle that’s been making head-
cells (more on that later), among lines in recent months — and that is the
myriad other innovations, the way we connection between meaningful social
look at longevity is evolving like never before. interactions and longevity. Verdin elab-
In fact, aging well is something people orates: “If you adopt a lifestyle that is
as young as their 20s are now taking into incompatible with friendship, you’re prob-
account. “There’s a lot of misinformation — ably hurting yourself. Friendship and our
this idea that research on aging science is sense of purpose are two of the major
focused on making rich people live longer determinants of healthspan and life span,
or that we’ll be able to live to 1,000. There which is why this pandemic is so toxic for
is nothing that tells us that we’re going to the elderly; they’re isolated from their
get that kind of life extension. However, families and friends.” Understanding the
living healthily to 100, I’m convinced this is different factors that affect aging and
something that most of us can do today,” their connection to each other is vital to
says Eric Verdin, M.D., CEO and president increasing the number of healthy years we
of the Buck Institute for Research on Aging spend at the end of our lives.
(www.buckinstitute.org), an independent And in Marin, with our outdoor lifestyle,
biomedical research institute that studies ease in securing healthy food and strong
aging and age-related disease in Novato. sense of community, increasing those years
According to Verdin, 90 percent of your is a relatively easy thing to do. While the
healthspan (the portion of your life span national average life span is 78 years old, in
spent in good health) is determined by Marin County the average life expectancy
environmental factors like food choices, is 87. “I would predict that if we were to
exercise and sleep, while only 10 percent take everyone and optimize them, we could
is predetermined by your genetics. “That probably bring average life expectancy
really puts the whole issue of healthspan from 87 to 95 — so we’re not so far from
squarely in your own lap,” says Verdin. And 100,” Verdin adds, “and that is amazing.”
the earlier you start caring about that, In the pages that follow, we explore
the better. some of the groundbreaking work the
There is a lot of conflicting informa- scientists who are leading the way in aging
tion when it comes to eating well, getting science are doing.
marin living. january/february 2021 45
“Any tissue
or system that has
estrogen or progesterone
responsiveness —
cardiovascular system,
brain, immune cell
function and bone health —
would be positively
influenced if we were
able to delay the onset
of menopause.”
Francesca Duncan, Ph.D.
The Center for Reproductive Longevity and Equality
investigates the correlation between reproductivity
important. Smoking and environmental
and aging in women.
pollution can have negative impacts on
reproductive health as well.
What does the term “equality” in the name provide for women as they age? What are the negative implications of
of the center refer to? There is a lot of data that shows that meno- women being able to bear children into
Illustration by Emily Blevins; portrait courtesy of the Buck Institute
Women are aging much earlier than men pause accelerates aging phenotypes. This their 50s and beyond?
in terms of their reproductive capacity, is largely related to the fact that you have I don’t think it’s our goal to help women
which includes the hormones produced reduced estrogen, which is so important to get pregnant in their 60s or 70s. There
by the ovary. Those hormones are crit- the functioning of other organ systems. Any are issues with getting pregnant and the
ical for the functioning of downstream tissue or system that has estrogen or burden of carrying a pregnancy at that
organ systems. This fact runs up against progesterone responsiveness — cardiovas- age has its own challenges. Right now,
the reality that many women need to cular system, brain, immune cell function we’re seeing women in their 30s and 40s
put off having children to make room and bone health — would be positively having trouble with fertility and using
for their careers — and that the delay influenced if we were able to delay the assistive reproductive technologies to
causes women to suffer the consequences onset of menopause. get pregnant. I would love to help those
of infertility that often happens with women conceive naturally. Additionally,
advanced reproductive age. Men don’t Are there lifestyle changes a woman we may be able to optimize endocrine
have that disadvantage; they can repro- can make to slow down the rate that her function during aging, without impacting
duce throughout their life span. fertility declines? fertility. That could provide significant
We know that conditions like obesity and health benefits to women throughout
If scientists were able to delay menopause, diabetes can have a negative impact on their life span, including the years
what health benefits could this potentially gamete health and fertility, so diet is really after childbearing.
46 january/february 2021 marin living.
a high-dose vitamin D displayed signs of
diabetes as they aged. This only seemed
to occur in the Alzheimer’s mice and not in
their normal siblings. We found that this
was accompanied by distinct changes in
the gut microbiota that appear to selec-
tively drive the mice into a diabetes-like
state. Vitamin D deficiency has been
linked to Alzheimer’s, leading to a rising
Julie Andersen, Ph.D. concern that older individuals may be
self-medicating to avoid risk of diabetes,
resulting in consumption of large dosages,
Studying the quest for new ways to prevent and of which the potential negative conse-
quences are currently unknown. We think
cure neurodegeneration, with a particular focus
that this could have important implica-
on Alzheimer’s and Parkinson’s diseases. tions given that diabetes is a major risk
factor for Alzheimer’s.
What are some of the discoveries that data we’ve collected so far suggests that How much of a factor is lifestyle — even
have been unearthed with the funds from UA is neuroprotective. for younger people — when you talk
the NIA $3.4 million grant? One of the things we’re really inter- about developing diseases like Alzhei-
We received funds from the National Insti- ested in testing is whether we can restore mer’s and Parkinson’s?
tute on Aging (NIA) to test the efficacy of production of UA by introducing a more It’s huge. A NIA-funded study published
a natural dietary gut flora–derived metab- youthful microbiome to the older mice this past June in the journal Neurology
olite called urolithin A (UA) in slowing or as they begin presenting with Alzhei- showed that people who engaged
preventing the presentation of Alzheimer’s mer’s. Results from these studies would in regular physical activity, did not
disease. UA is metabolized in the gut from further our understanding of how rein- smoke, consumed light-to-moderate
a precursor called ellagic acid (EA), which stating a more youthful microbiome amounts of alcohol, ate a high-quality
is found in several health foods including restores gut-brain signaling and protects diet, and engaged in cognitive activi-
Illustration by Emily Blevins; Jim Hughes Photography
pomegranates, berries and walnuts, to brain neurons. ties had a 60 percent reduced risk for
name just a few. developing Alzheimer’s.
As they age, the mice we are studying Have you discovered anything completely Parkinson’s has also been associ-
display plaques and tangles as well as unexpected? ated with environmental factors such
losses in cognitive function similar to We had expected that UA would elicit as increased exposure to pesticides and
those observed in human Alzheimer’s neuroprotection, but what’s really exciting a high-fat diet and is slowed by phys-
patients. Studies have already shown that about our initial results is that it looks like ical exercise and increased consump-
our microbiome — the bacteria, fungi, we’ve been able to identify a dosage that tion of beverages like tea, coffee and
protozoa and viruses that live inside our works. This is extremely helpful in terms antioxidant-containing foods. Physical
gut — may play a role in neurological of UA’s potential use in treating diseases exercise including aerobics, resistance
conditions such as autism, epilepsy and like Parkinson’s and Alzheimer’s. In a sepa- training and stress management via mind-
depression. We hypothesized that oral rately funded study, we looked at the effi- body practices including meditation,
administration of UA would slow the onset cacy of megadose vitamin D. Here, we saw yoga, tai chi and dance have also been
of Alzheimer’s. It’s still early days, but the something very surprising — the mice on suggested to be beneficial.
marin living. january/february 2021 47
“A number of laboratories have shown that at
least two interventions — each known to promote
healthy aging — also reduce the abundance of
senescent cells ... caloric restriction and exercise.”
Judith Campisi, Ph.D. are indeed causal for a surprisingly large
number of human age-related diseases,
ranging from neurodegeneration to late-
Understanding cellular senescence, the cause of chronic life cancer. Fewer studies have used seno-
inflammation connected to many age-related diseases. lytic drugs (which kill senescent cells), but
those results support this conclusion. That
is, eliminating senescent cells can either
delay the onset, ameliorate the severity, or,
Can you explain what cellular SASP factors, and those change over time. in some cases, reverse the manifestation of
senescence is? However, senescent cells and the SASP many age-associated diseases.
When cells become senescent, they can and do, under certain circumstances, Two important lessons we’ve learned
acquire three new features: they stop have beneficial effects. Examples include from the above studies. First, senescent
dividing; they become somewhat resistant certain times during embryogenesis and cells are almost always rare, comprising
to dying; and they secrete many bioactive during wound healing and tissue repair. only a small percentage of cells in any
molecules (the senescence-associated Thus, it is important to know when and tissue. Second, in transgenic mice it is not
secretory phenotype or SASP). The SASP where and what type of senescent cells necessary to kill all senescent cells in order
seems to be particularly important for are present in order to understand their to delay, ameliorate or reverse age-related
driving aging because it includes a large role in aging and disease. diseases. Generally, eliminating 70 to 80
number of factors that promote inflam- percent of senescent cells is sufficient.
mation. Low-level chronic inflammation is What is the correlation between senes-
a hallmark of aging tissues (and has been cent cells and disease? Are there any external factors that
termed “inflammaging”). Inflammation, The correlation is excellent — in mice, affect the aging of senescent cells in
while an essential process during tissue humans and other mammals, even in younger people?
repair, can be destructive to tissue struc- zebra fish. But correlation does not prove A number of laboratories have shown that
ture and function when it is chronic. causality. However, transgenic [geneti- at least two interventions — each known
Senescence is hard to study because cally modified] mouse models now exist to promote healthy aging — also reduce
there are no specific senescence where it is possible to selectively elimi- the abundance of senescent cells, or at
markers. Also, each cell type differs nate senescent cells at any point in the least the abundance of cells that express
from others with regard to the genes it life span. Experiments using these mice detrimental (inflammatory) SASP factors:
expresses, especially genes encoding clearly demonstrate that senescent cells caloric restriction and exercise.
Illustration by Emily Blevins; Jim Hughes Photography
48 january/february 2021 marin living.
Brianna
Stubbs,
Ph.D.
The lead translational
scientist in Ketones Lab
is using the body’s own
metabolic signals to
increase longevity.
Can you explain what a ketone is?
Ketones are a family of compounds that
our body can break down for energy
instead of its usual fuels, glucose (sugar) or
fat. The main reason that ketones exist is
to fuel our brain when we are running low It is early days, but research shows that know for sure yet if and how ketones
on glucose stores. Our body only makes ketones have promise to treat some of the could interact with the disease process
ketones when glucose stores are running common diseases of aging such as heart of Covid-19. From our knowledge of the
low, such as if you follow a very low carbo- failure and neurodegeneration. basic science of ketones we suspect that
hydrate diet or if you don’t eat any food for they could interact with some aspects of
more than a day or so. Until recently, the Your lab is working on a supplement to the immune system (i.e., inflammation
only way to raise the amount of ketones in mimic the effects of the ketogenic diet — and oxidative stress), which might help
the blood was to follow a low-carbohydrate can you tell us more about that? with the response to infection. While we
diet or fast, but now scientists are devel- We have developed a new form of edible suspect that could have a positive effect,
oping drinkable ketones that can give the ketone, called a ketone ester. This is a there are also ways in which these ketone
body access to ketones without any other compound that breaks down inside the effects could be counterproductive. We
dietary changes. body and raises the levels of ketones in the need to do more research to be sure, but
Illustration by Emily Blevins; portrait courtesy of the Buck Institute
blood without the person having to follow it is an interesting possibility.
How do ketones play a factor in the way a ketogenic diet or undertake fasting. It Ketones might also be helpful in miti-
the body responds to stressors and how also works very quickly and doesn’t rely gating some of the conditions that come
might they improve healthspan? on fat breakdown like the ketogenic diet. alongside being in intensive care with a
Situations that cause the body’s carbohy- We think that having ketones in the blood disease like Covid-19. ICU patients have
drate stores to run out are stressful, espe- could be helpful for some aspects of health a high rate of heart damage, delirium and
cially when we think about ketones in the and longevity, and you might be able to also muscle wasting — there is mechanistic
context of starvation. It is important that the get some of these benefits just by drinking evidence to support the use of ketones
body turns on a coordinated set of processes ketone esters without needing to follow the to prevent these side effects. But again,
that protect it from rapid breakdown and ketogenic diet. The ketone ester will be the intensive care is a complex set of stressors
would help us to survive long periods of main ingredient of a new product, Meta- and we can’t be sure if the net effect would
starvation. In that regard, the presence of bolic Switch, that is being released this be positive or negative until we test this in
ketones is part of the way the body signals year by a company called Juvenescence. a carefully controlled setting.
the need for self-preservation. Ketones
may help to switch on multiple pathways Are there any connections between The Buck Institute is a nonprofit
that cause cells to clean themselves up and ketones, Covid-19 and immunity? organization and relies on donations. To
regenerate; this could help with healthspan. It’s important to say that we really don’t get involved, visit www.buckinstitute.org.
marin living. january/february 2021 49
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