The Future of Aging and Longevity - Flipbook - Page 38
The Future
of Aging
Depends on
the Future of
Brain Health
Howard Fillit, MD
Miranda Orr, PhD
Co-Founder and Chief
Science O昀케cer Emeritus,
Alzheimer’s Drug Discovery
Founda琀椀on
Associate Professor of
Neurology and Co-Director
of the Tracy Family SILQ
Center, WashU Medicine
ver the past decade, the conversa琀椀on
about aging has changed. People are
living longer, but along with this comes a
fear of cogni琀椀ve decline. Our goal cannot be simply
to extend lifespan; it must be to extend healthspan,
with brain health at the center, so we can maintain
our quality of life and age with dignity and grace.
Brain health is more than the absence of
demen琀椀a. It re昀氀ects the resilience of the brain across
decades—the ability to maintain cogni琀椀on, adapt
to stress, preserve neural circuits, and recover from
injury. As our understanding of aging advances,
preserving brain health may become one of the most
important measurable indicators of healthy aging.
Nowhere is this more urgent than Alzheimer’s
disease, one of the clearest examples of how aging
drives chronic condi琀椀ons. The past decade has
brought real progress, including the 昀椀rst diseasemodifying therapies, but it has also clari昀椀ed a larger
lesson: Alzheimer’s is not a one-pathway disease. If
we priori琀椀ze only amyloid, the focus of the 昀椀eld for
much of its history, we may win that ba琀琀le but lose
the larger war on Alzheimer’s.
Today, Alzheimer’s is increasingly understood
as a complex disease of aging biology, shaped by
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in昀氀amma琀椀on, metabolic dysfunc琀椀on, oxida琀椀ve
stress, synap琀椀c failure, and other interrelated
processes. Pathology can appear 15 to 20 years
before symptoms emerge, and the biological changes
that set the disease in mo琀椀on may begin even earlier.
Understanding these upstream drivers is just as
cri琀椀cal as understanding the pathology itself and
addressing them represents a fundamental shi昀琀 from
reac琀椀ng to disease a昀琀er it emerges to preserving the
biology that supports brain health throughout aging.
This broader view has moved from the margins
to the center of the 昀椀eld. Since its founding nearly
30 years ago, the Alzheimer’s Drug Discovery
Founda琀椀on has championed the idea that
Alzheimer’s must be understood through its full
pathobiology. At the 琀椀me, that approach was
outside the mainstream. Today, roughly 75 percent
of Alzheimer’s clinical trials target pathways beyond
amyloid and tau, re昀氀ec琀椀ng a 昀椀eld that is 昀椀nally
catching up to the complexity of the disease.
This shi昀琀 is also re昀氀ected in a new genera琀椀on of
inves琀椀gators who are framing Alzheimer’s through
the biology of aging rather than a single disease
pathway. Cellular senescence is one example. As
cells age, some become dysfunc琀椀onal and can alter
MIL K EN I N S T I T U T E | T H E FU T U RE O F AGI N G A N D LO N GEV I TY
