# Boston OAIC: A Translational Approach to Function Promoting Therapies

> **NIH NIH P30** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $426,342

## Abstract

ABSTRACT
The geroscience hypothesis (i.e., that multiple age-related conditions result from a finite set of evolutionarily
conserved molecular processes) implies a dynamic balance between gerodrivers and geroprotectors over the
life course. In the context of HIV, older persons living with HIV (PWH) are disproportionately burdened with
age-related conditions and multimorbidity, including significant declines in functional capacity underscoring the
need for geroprotectors. NAD+ is a key cofactor, both in cellular energy metabolism and in modulation of
inflammatory signaling. In multiple species, NAD decline with age has been linked to deficits in mitochondrial
function and metabolic capacity, and decline in the activity of sirtuins, a class of NAD+-dependent enzymes that
control inflammation, mitochondrial metabolism and aging. Thus, repletion of NAD is an attractive therapeutic
modality for potentially reducing age-related inflammation (i.e., inflammaging) and improving physical function.
 Our preliminary studies indicate that circulating concentrations of NAD, NMN and the NAD metabolome
can be measured in blood using liquid chromatography tandem mass spectrometry and that MIB-626 1000-mg
once daily or twice daily regimens were safe and associated with substantial dose-related increases in blood
NAD levels and its metabolome (Fig 1) [1]. We also show that NAD levels were lower in monocytes (Fig 2) and
skeletal muscle (Fig 3) in persons with chronic HIV infection from our MATCH cohort [2]. We also show that
NAD levels in skeletal muscle were negatively correlated with inflammation (Fig 4) [2]. We also observed loss
in endurance in MATCH participants based on a constant work rate treadmill fatigability test (Fig 5). Our prior
studies have shown that older persons with HIV display bioenergetic deficits [3-5], including decline in physical
activity (PA) based on objective assessment of free-living activity using wearable technology [3, 6], and we
also recently observed declines in cognitive performance in PWH compared to uninfected [7].
 The hypothesis tested in this proposal is that NAD levels in older persons with chronic HIV infection will be
lower when compared to uninfected age-matched persons and will be associated with epigenetic changes in
genes involved in the regulation of metabolic, inflammatory, and mitochondrial bioenergetic pathways, and with
impairment of insulin sensitivity and whole person functional outcomes; including lab based measures of
endurance and muscle fatigability and objective measures of PA using wearable technology.

## Key facts

- **NIH application ID:** 10610008
- **Project number:** 3P30AG031679-12S2
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** SHALENDER BHASIN
- **Activity code:** P30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $426,342
- **Award type:** 3
- **Project period:** 2008-09-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10610008

## Citation

> US National Institutes of Health, RePORTER application 10610008, Boston OAIC: A Translational Approach to Function Promoting Therapies (3P30AG031679-12S2). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10610008. Licensed CC0.

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