# Biopsychosocial Mechanisms of Successful Aging

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $811,526

## Abstract

It is well-known that in most people, cognitive abilities decline with age. With the elderly population growing
(20% of Americans will be over 65 by 2030), this represents a significant public health concern. However, not
all older adults show this pattern of decline. We and others have demonstrated that some individuals seem to
be resilient to age-related decline, even in the setting of biomarkers of Alzheimer’s disease (AD)
neuropathologic changes. Understanding the factors that promote resilience in older adults could point to new
approaches to achieve healthy aging in all adults.
In our recent studies of aging, we identified substantial heterogeneity within older adults in memory
performance and both brain anatomy and connectivity, such that some older participants (60-80 yrs.) were
indistinguishable from young adults (18-32). These remarkable individuals offer the opportunity to investigate
the biobehavioral mechanisms that contribute to successful aging.
Our findings indicated that successful agers (who showed preserved anatomy within and connectivity between
multiple limbic and paralimbic structures that subserve motivation, affect, and cognition) exhibited a distinct
neural response to challenging tasks when compared to typical agers. Crucially, successful agers also differed
in their subjective experience of the task, rating the arousal caused by the task as significantly more pleasant.
Together, these results suggest that individual differences in the response to increasing arousal during difficult
cognitive tasks contribute meaningfully to cognitive outcomes in aging.
Here, we introduce the Arousal along the Challenge/Threat Continuum (ACT-C) model, which hypothesizes
that arousal can be helpful or harmful to cognition, depending on how it is expressed in the brain and the body
In this proposal, we will test the central hypothesis of the ACT-C model, that individual differences in the
experience of affect, and its neurobiological and autonomic physiological correlates predicts cognitive
performance in aging. We propose that increased effort and cognitive performance will be associated with a
tendency to subjectively experience arousal more as challenge than as threat (Aim 1), an autonomic
physiological response to difficult tasks previously associated with a challenge interpretation (i.e. decreased
vascular resistance, Aim 2), and a neural ‘challenge’ pattern involving increased mid-cingulate activity and
communication between networks (Aim 3). Crucially, we predict that these motivational, physiological, and
neural factors will be associated with improved performance even in individuals with evidence of preclinical AD.
This research, if successful, will provide much-needed insight into the biological mechanisms by which affect
and motivation support cognitive aging. The outcomes of this research could point the way to neural and
physiological biomarkers predicting successful aging, which could be used to evaluate interventions to prom...

## Key facts

- **NIH application ID:** 10367055
- **Project number:** 1R01AG071173-01A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Lisa Feldman Barrett
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $811,526
- **Award type:** 1
- **Project period:** 2022-02-15 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10367055

## Citation

> US National Institutes of Health, RePORTER application 10367055, Biopsychosocial Mechanisms of Successful Aging (1R01AG071173-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10367055. Licensed CC0.

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