{ LIFE SCIENCES }

Reducing the Impact of Brain Aging

A gift from the Vranos Family Foundation is bringing together researchers from the Faculty of Arts and Sciences and Harvard Medical School to mitigate age-related neurodegenerative diseases

Reducing the Impact of Brain Aging

Reducing the Impact of Brain Aging

{ Life Sciences }
September 22, 2023

While many people are living longer than ever before, they’re also at greater risk of developing chronic, incurable age-related diseases of the central nervous system, such as Parkinson’s and Alzheimer’s, as well as what’s referred to as “normal” cognitive decline. In the U.S. alone, more than 10 million individuals experience at least one of these conditions.

Over the past few years, there has been encouraging progress in understanding the biology of aging. Several labs at Harvard—including those of Lee Rubin, co-leader of the Nervous System Diseases Program at the Harvard Stem Cell Institute (HSCI) and a professor in the Department of Stem Cell and Regenerative Biology (HSCRB); Richard Lee, professor in HSCRB and a professor of medicine at Harvard Medical School (HMS); and Amy Wagers, co-chair of HSCRB and the Forst Family Professor in HSCRB—were among the first in the world to establish how certain blood factors can influence aging. Their research supports the idea that it may be possible in the not-so-distant future to formulate novel strategies for reducing the devastating consequences of brain aging and its connection to prevalent neurodegenerative diseases.

An early philanthropic supporter of this groundbreaking work at Harvard, Michael Vranos AB ’83 and the Vranos Family Foundation are building on the momentum of these discoveries. A gift from the foundation will enable Harvard researchers to combine the most advanced experimental methods with a dedicated computational effort to pursue approaches that can potentially halt the functional decline associated with aging.

“The Vranos Family Foundation is proud to support researchers from the Faculty of Arts and Sciences and Harvard Medical School in their work to challenge the impacts of brain aging,” says Vranos. “Tackling life-altering neurodegenerative diseases that result from brain aging is critical, and we are pleased to fund science that we believe will lead to actionable therapeutic approaches in the future. We are honored to play a small role in helping advance this research, which aligns with our mission of backing initiatives with a focus on health care, education, human services, children’s services, and international relief.”

“Tackling life-altering neurodegenerative diseases that result from brain aging is critical. We are honored to play a small role in helping advance this research.”

— MICHAEL VRANOS AB ’83

The gift will provide support for investigators across the Faculty of Arts and Sciences (FAS) and HMS, including Lee Rubin; Paola Arlotta, Golub Family Professor and co-chair of HSCRB and a principal faculty member at HSCI; Randy Buckner, Sosland Family Professor of Psychology and of Neuroscience; Isaac Kohane, Marion V. Nelson Professor and chair of the Department of Biomedical Informatics at HMS; and Chirag Patel, associate professor of biomedical informatics at HMS.

Through laboratory experiments and computational analyses, the project will seek to answer several important questions, such as whether it’s possible to have a more unified understanding of aging reversal that can lead to potent methods of improving brain function.

It will also focus on the different pathways of aging among individuals, looking at how potential determinants, such as ancestry and ethnicity, might affect a person’s risk of having an age-related disease.

Additionally, it will aim to formulate therapeutics that can shift the “transcriptional state” of brain cells—the conversion of DNA to RNA to prompt gene activity—to improve the function of the aging brain and reduce the impact of degenerative disorders.

“We expect that this work will produce not only excellent science but clear, actionable, therapeutic approaches that can advance to the clinic,” says Rubin, director of the project. “Our ultimate goal is to combine this research with the work of other Harvard colleagues who investigate health economics, health policy, and societal disparities in aging with a view toward having a strong positive impact on our aging society.”

Meeting of the Minds

The gift from the Vranos Family Foundation is propelling the work of researchers at the FAS and HMS, whose scholarship over the years has expanded our understanding of how the brain functions and potential interventions to improve brain health.

LEE RUBIN
LEE RUBIN
PAOLA ARLOTTA
PAOLA ARLOTTA
RANDY BUCKNER
RANDY BUCKNER
ISAAC KOHANE
ISAAC KOHANE
CHIRAG PATEL
CHIRAG PATEL

Lee Rubin is broadly interested in the mechanisms underlying the deterioration of the nervous system caused by aging or disease, as well as the interactions between the nervous system and the rest of the body that mediate health. His lab is studying how factors that circulate in blood affect the aging brain, as well as how the gut microbiome influences the brain and how it changes over time, especially in conditions of inflammation. Building on the work of colleagues Richard Lee and Amy Wagers, Rubin found in mouse studies that the protein GDF11 stimulates the growth of new blood vessels in the hippocampus, a part of the brain associated with learning and memory. Founded by Rubin, Lee, and Wagers, the pharmaceutical startup Elevian is developing a GDF11-based therapy—scheduled to enter clinical trial in 2023—to stimulate recovery of damaged brain tissue after stroke.

Paola Arlotta’s research is focused on brain organoids—three-dimensional tissues grown from human stem cells that mimic aspects of an actual brain. The organoids Arlotta builds model the cerebral cortex, which is responsible for higher functions including language, memory, emotion, decision-making, and personality. Much of the work in Arlotta’s lab aims to figure out what happens in cases of autism, schizophrenia, and dementia and how doctors might someday intervene. Arlotta and Rubin are exploring aging human brain organoids and have just completed their first joint experiment, which is currently being analyzed.

Randy Buckner’s laboratory uses multiple behavioral, neuroimaging, and computational approaches to look at the organization and function of large-scale human brain networks that contribute to high-level cognition, as well as how genetic variation gives rise to differences that affect behavior. Understanding how brains become disordered may shed light on neuropsychiatric and neurodegenerative disorders. Recently his work has expanded to explore the detailed organization of individual brains and how that organization differs across people and changes over time. This work includes clinically normal older adults who harbor preclinical markers of Alzheimer’s.

Isaac Kohane and Chirag Patel, together with Rubin, are pursuing cutting-edge research in single-cell transcriptomics—which examines the gene expression level of individual cells—with a specific focus on aging. Their collaborative effort aims to advance our understanding of the molecular mechanisms underlying aging and age-related diseases.

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