Dr. Christin Glorioso is a neuroscientist, founder
and CEO of NeuroAge Therapeutics (@NeuroAgeTX), &
Co-Founder and CEO of Academics for the Future of Science,
a science advocacy and research non-profit. She specializes
in Alzheimer's disease and aging.
I have been asked a lot recently about what I think of Peter
Attia’s NY Times bestselling book on longevity
medicine, Outlive. So I decided to take a read to be
able to answer this question, inform myself about what is in
the popular press, and make a reasonable recommendation to read
this book (or not).
On
a high level, I think this book is important conceptually and
represents a profound shift in medicine that is much needed.
I am eager for the public to embrace “Medicine 3.0”
and start seeing disease as a continuum that starts with aging
in your twenties- and is something that can be abrogated to
a large degree by lifestyle interventions. I agree with about
95% of the content. I think it leaves out a few things (including
most of the scientific advancements in the field around reprogramming
and regeneration) and there are some parts that I disagree with
from a medical and scientific perspective- mostly surrounding
supplements and drugs (which he claims not to go into but then
does go into to some extent).
From
a reader perspective, all but the last two chapters were a slog.
This maybe gets explained in the epilogue when he says that
the book’s first draft was super technical and then he
enlisted a co-author to make it into more of a personal story.
I think I would have preferred a condensed technical manual
that was about 1/3 of the length or better yet, an outline with
bullet points (which I created for you to some extent below).
I found myself skimming through the “too general”
to be interesting patient and scientist anecdotes to get to
the actual medical recommendations. This is with the exception
of the last two chapters- those were actually compelling to
read. Those chapters were a personal story about Attia’s
own trauma and struggles with mental health. I think the points
made in those chapters were not only compelling to read but
also highlighted a missing fundamental piece about the longevity
conversation. They could have been the start of a different
book.
One
device that stuck in my craw was Attia repeatedly referring
to himself as “not thin Peter.” This was a reference
to an unkind comment his wife made to him about needing to lose
some weight. This comment was never explained as her concern
for his health and left me thinking that she was complaining
about his physical appearance from an attractiveness perspective.
And if you google pics of Attia, which I did, you’d be
hard pressed to find one where he looks to be overweight. So
every time he would shame himself by calling himself “not
thin Peter” (possibly in an attempt to be self-deprecating
and therefore relatable to the reader or just because it is
a negative narrative that genuinely drives him), I felt vicariously
body shamed, a feeling that wasn’t pleasant to have to
continually endure.
In
general, this also speaks to the current incarnation of longevity
medicine that has a large superficial streak and one that also
seems very privileged. Another piece of the conversation that
was missing was one about access and disparities in medicine.
The mental health chapters in particular were glaringly obtuse
to this. Attia’s journey towards better mental health
involved unfettered access to out of pocket sessions with five
of the most famous therapists in the world, including Esther
Perel (I’m a big fan of her) and stays at expensive private
pay clinics. If this is what the journey to mental longevity
requires, then almost no one has access. This is a point that
at least should have a few sentences to acknowledge. Attia’s
story was vulnerable and brave, but also so so privileged.
“I
believe that our goal should be to act early as possible, to
try to prevent people from developing type 2 diabetes and all
the other horsemen [diseases of aging]” . . . Medicine
3.0 places a far greater emphasis on prevention than treatment.
When did Noah create the ark? Long before it began to rain.
Medicine 2.0 tries to figure out how to get dry before it starts
raining. Medicine 3.0 studies meteorology and tries to determine
whether we need to build a better roof, or a boat.”
QUOTES
“Exercise
is by far the most potent longevity “drug”1000%
“striving
for physical health is meaningless if we ignore our mental
health”
“There
are many examples of how Medicine 2.0 gets risk wrong, but
one of the most egregious has to do with hormone replacement
therapy (HRT) for postmenopausal women” [interpretations
of the WHI wrongly discouraged use of HRT]- Yes.
We
need tools with a much longer reach than relatively brief
clinical trials.
“Mendelian
randomization helps tease out causal relationships between
modifiable risk factors” 1000%- AI is the answer to
much of this.
The
older you get, the more genetics matters for longevity.
Pro
preventative cancer screening using liquid biopsy.
Pro
preventative screening using whole body MRI.
All
of the Alzheimer’s chapter is spot on except that we have
no approved amyloid drugs (we have two) and he misses the “Alzheimer’s
is an aging program” theory of what causes it- which is
the theory that I firmly believe in.
I’m
glad he realizes that he contributed to the keto diet craze
and that was potentially harmful to many people.
Loved
the discussion of CR and the two conflicting primate studies.
“the
best nutrition plan is the one that we can sustain” --
basically we need to eat a normal amount of calories -- the
particulars of how we do that doesn’t matter that much.
Sleep
deprivation is a huge problem for health, and dangerous for
patients of sleep deprived clinicians. It’s not a badge
of honor. Yes.
THE
DISAGREE COLUMN:
On
longevity science: “On the other end of the spectrum are
those convinced that science will soon figure out how to unplug
the aging process itself, by tweaking some obscure cellular
pathway, or lengthening our telomeres, or “reprogramming”
our cells so that we no longer need to age at all. This seems
highly unlikely in our lifetime, although it is certainly true
that science is making huge leaps in our understanding of aging
and of the Horsemen of disease”
These
pathways may seem obscure to Attia because he is not a scientist.
To those in the biotech and scientific fields, these are not
obscure at all but actionable pathways where in some case drugs
are currently in phase 2 clinical trials. Or they are currently
approved drugs- in the case of PI3K. I would put the timeline
for the first longevity drugs to be in the next decade- definitely
a longevity pathway, likely reprogramming. If you want to learn
more about the exciting science and biotech in the longevity
space, check out the videos on Longevity Global YouTube.
Centenarians
and smoking: this is not exactly a point of disagreement but
there is a link between longevity and smoking in super centenarians
and I don’t think this is an accident. People die increasingly
from neurodegenerative diseases in the oldest ages and smoking
is linked to less Parkinson’s disease. That’s not
to say that we all should smoke- definitely not- smoking causes
lung cancer and heart disease. But in people above a certain
age- say 80 years old- we should consider creating nicotine
pathway drugs or prescribing nicotine patches- my two cents.
I think this has been wildly understudied.
Attia
promotes a “mouse-centric” view of popular longevity
drugs and supplements, rapamycin, resveratrol, and NR, and metformin.
Attia notes that mice are not humans but then only seems to
hang his hat on the mouse studies, largely ignoring invertebrates
and human studies. 90% of drugs that pass mouse studies fail
in human clinical trials. I would pay a lot more attention to
human data than mouse data to understand what’s what with
regard to these drugs.
Metformin:
Attia himself has backpedalled on promoting Metformin for longevity
in his blog but basically promotes it in this book. I am against
people taking Metformin when they don’t have diabetes.
The primary reason for this is multiple clinical trials pointing
to a potential increase in risk of Parkinson’s disease
in metformin users.
Measuring
aging: “aging itself is difficult— if not impossible—
to measure with any accuracy” I completely disagree with
this statement. Aging clocks and other biomarkers are being
developed to measure aging and are relatively easy good approximates
of aging and disease risk. See also here for an NIH blog post
on some recent research on this out of the Wyss-Coray lab at
Stanford.
Statins
are safe at high levels to lower cholesterol to levels that
children have. I think this is overkill and not proven to be
safe. Children fundamentally have different biology than adults
because they are still developing. I think ideal cholesterol
levels are those of a fit person in their twenties and we should
not use drugs to go below that level.
Every
single amyloid drug for Alzheimer’s has failed—
not true we have had two approved drugs last year including
Lilly’s Lecanemab.
He
has a negative view of yoga- calling people “yoginis”
disparagingly and failing to recognize the literature on its
benefits for flexibility, stability and mental health.
