TY - JOUR
T1 - Pharmaceutical and nutraceutical activation of FOXO3 for healthy longevity
AU - McIntyre, Rebecca L.
AU - Liu, Yasmine J.
AU - Hu, Man
AU - Morris, Brian J.
AU - Willcox, Bradley J.
AU - Donlon, Timothy A.
AU - Houtkooper, Riekelt H.
AU - Janssens, Georges E.
N1 - Funding Information: MH is supported by a Chinese Science Council scholarship. The work of BJM, TAD and BJW is supported by the US National Institutes of Health (contract N01-AG-4–2149 , Grants 5 U01 AG019349–05 , 5R01AG027060 [Kuakini Hawaii Lifespan Study], 5R01AG038707 [Kuakini Hawaii Healthspan Study], and contract N01-HC-05102 from the National Heart Lung and Blood Institute . GEJ is supported by a VENI grant from ZonMw, Talent Development and Innovation grants from the AGEM institute, and a Longevity Impetus Grant from Norn Group. Publisher Copyright: © 2022
PY - 2022/6/1
Y1 - 2022/6/1
N2 - Life expectancy has increased substantially over the last 150 years. Yet this means that now most people also spend a greater length of time suffering from various age-associated diseases. As such, delaying age-related functional decline and extending healthspan, the period of active older years free from disease and disability, is an overarching objective of current aging research. Geroprotectors, compounds that target pathways that causally influence aging, are increasingly recognized as a means to extend healthspan in the aging population. Meanwhile, FOXO3 has emerged as a geroprotective gene intricately involved in aging and healthspan. FOXO3 genetic variants are linked to human longevity, reduced disease risks, and even self-reported health. Therefore, identification of FOXO3-activating compounds represents one of the most direct candidate approaches to extending healthspan in aging humans. In this work, we review compounds that activate FOXO3, or influence healthspan or lifespan in a FOXO3-dependent manner. These compounds can be classified as pharmaceuticals, including PI3K/AKT inhibitors and AMPK activators, antidepressants and antipsychotics, muscle relaxants, and HDAC inhibitors, or as nutraceuticals, including primary metabolites involved in cell growth and sustenance, and secondary metabolites including extracts, polyphenols, terpenoids, and other purified natural compounds. The compounds documented here provide a basis and resource for further research and development, with the ultimate goal of promoting healthy longevity in humans.
AB - Life expectancy has increased substantially over the last 150 years. Yet this means that now most people also spend a greater length of time suffering from various age-associated diseases. As such, delaying age-related functional decline and extending healthspan, the period of active older years free from disease and disability, is an overarching objective of current aging research. Geroprotectors, compounds that target pathways that causally influence aging, are increasingly recognized as a means to extend healthspan in the aging population. Meanwhile, FOXO3 has emerged as a geroprotective gene intricately involved in aging and healthspan. FOXO3 genetic variants are linked to human longevity, reduced disease risks, and even self-reported health. Therefore, identification of FOXO3-activating compounds represents one of the most direct candidate approaches to extending healthspan in aging humans. In this work, we review compounds that activate FOXO3, or influence healthspan or lifespan in a FOXO3-dependent manner. These compounds can be classified as pharmaceuticals, including PI3K/AKT inhibitors and AMPK activators, antidepressants and antipsychotics, muscle relaxants, and HDAC inhibitors, or as nutraceuticals, including primary metabolites involved in cell growth and sustenance, and secondary metabolites including extracts, polyphenols, terpenoids, and other purified natural compounds. The compounds documented here provide a basis and resource for further research and development, with the ultimate goal of promoting healthy longevity in humans.
KW - Aging
KW - DAF-16
KW - FOXO3
KW - Geroprotector
KW - Nutraceutical
KW - Pharmaceutical
UR - http://www.scopus.com/inward/record.url?scp=85128236345&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.arr.2022.101621
DO - https://doi.org/10.1016/j.arr.2022.101621
M3 - Review article
C2 - 35421606
SN - 1568-1637
VL - 78
SP - 101621
JO - Ageing Research Reviews
JF - Ageing Research Reviews
M1 - 101621
ER -