CD38 inhibitor 78c increases mice lifespan and healthspan in a model of chronological aging

Thais R. Peclat; Katie L. Thompson; Gina M. Warner; Claudia C.S. Chini; Mariana G Tarragó; Delaram Z. Mazdeh; Chunlian Zhang; Jose Zavala-Solorio; Ganesh Kolumam; Yao Liang Wong; Robert L. Cohen; Eduardo N. Chini

doi:10.1111/acel.13589

CD38 inhibitor 78c increases mice lifespan and healthspan in a model of chronological aging

Thais R. Peclat, Katie L. Thompson, Gina M. Warner, Claudia C.S. Chini, Mariana G Tarragó, Delaram Z. Mazdeh, Chunlian Zhang, Jose Zavala-Solorio, Ganesh Kolumam, Yao Liang Wong, Robert L. Cohen, Eduardo N. Chini

Anesthesiology

Research output: Contribution to journal › Article › peer-review

Abstract

Nicotinamide adenine dinucleotide (NAD) levels decline during aging, contributing to physical and metabolic dysfunction. The NADase CD38 plays a key role in age-related NAD decline. Whether the inhibition of CD38 increases lifespan is not known. Here, we show that the CD38 inhibitor 78c increases lifespan and healthspan of naturally aged mice. In addition to a 10% increase in median survival, 78c improved exercise performance, endurance, and metabolic function in mice. The effects of 78c were different between sexes. Our study is the first to investigate the effect of CD38 inhibition in naturally aged animals.

Original language	English (US)
Article number	e13589
Journal	Aging Cell
Volume	21
Issue number	4
DOIs	https://doi.org/10.1111/acel.13589
State	Published - Apr 2022

Keywords

CD38
NAD
aging
healthspan
longevity
mice
small molecule

ASJC Scopus subject areas

Aging
Cell Biology

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10.1111/acel.13589

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title = "CD38 inhibitor 78c increases mice lifespan and healthspan in a model of chronological aging",

abstract = "Nicotinamide adenine dinucleotide (NAD) levels decline during aging, contributing to physical and metabolic dysfunction. The NADase CD38 plays a key role in age-related NAD decline. Whether the inhibition of CD38 increases lifespan is not known. Here, we show that the CD38 inhibitor 78c increases lifespan and healthspan of naturally aged mice. In addition to a 10% increase in median survival, 78c improved exercise performance, endurance, and metabolic function in mice. The effects of 78c were different between sexes. Our study is the first to investigate the effect of CD38 inhibition in naturally aged animals.",

keywords = "CD38, NAD, aging, healthspan, longevity, mice, small molecule",

author = "Peclat, {Thais R.} and Thompson, {Katie L.} and Warner, {Gina M.} and Chini, {Claudia C.S.} and Mariana G Tarrag{\'o} and Mazdeh, {Delaram Z.} and Chunlian Zhang and Jose Zavala-Solorio and Ganesh Kolumam and {Liang Wong}, Yao and Cohen, {Robert L.} and Chini, {Eduardo N.}",

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year = "2022",

month = apr,

doi = "10.1111/acel.13589",

language = "English (US)",

volume = "21",

journal = "Aging Cell",

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AU - Peclat, Thais R.

AU - Thompson, Katie L.

AU - Warner, Gina M.

AU - Chini, Claudia C.S.

AU - Tarragó, Mariana G

AU - Mazdeh, Delaram Z.

AU - Zhang, Chunlian

AU - Zavala-Solorio, Jose

AU - Kolumam, Ganesh

AU - Liang Wong, Yao

AU - Cohen, Robert L.

AU - Chini, Eduardo N.

PY - 2022/4

Y1 - 2022/4

N2 - Nicotinamide adenine dinucleotide (NAD) levels decline during aging, contributing to physical and metabolic dysfunction. The NADase CD38 plays a key role in age-related NAD decline. Whether the inhibition of CD38 increases lifespan is not known. Here, we show that the CD38 inhibitor 78c increases lifespan and healthspan of naturally aged mice. In addition to a 10% increase in median survival, 78c improved exercise performance, endurance, and metabolic function in mice. The effects of 78c were different between sexes. Our study is the first to investigate the effect of CD38 inhibition in naturally aged animals.

AB - Nicotinamide adenine dinucleotide (NAD) levels decline during aging, contributing to physical and metabolic dysfunction. The NADase CD38 plays a key role in age-related NAD decline. Whether the inhibition of CD38 increases lifespan is not known. Here, we show that the CD38 inhibitor 78c increases lifespan and healthspan of naturally aged mice. In addition to a 10% increase in median survival, 78c improved exercise performance, endurance, and metabolic function in mice. The effects of 78c were different between sexes. Our study is the first to investigate the effect of CD38 inhibition in naturally aged animals.

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KW - aging

KW - healthspan

KW - longevity

KW - mice

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CD38 inhibitor 78c increases mice lifespan and healthspan in a model of chronological aging

Abstract

Keywords

ASJC Scopus subject areas

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