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Brett Black

New NIA "Interventions Testing Program" (ITP) mice lifespan results published

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1. Aging Cell. 2016 Jun 16. doi: 10.1111/acel.12496. [Epub ahead of print]

 

Longer lifespan in male mice treated with a weakly estrogenic agonist, an

antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer.

 

Strong R(1,)(2), Miller RA(3), Antebi A(4), Astle CM(5), Bogue M(5), Denzel

MS(4), Fernandez E(1,)(2), Flurkey K(5), Hamilton KL(6), Lamming DW(7), Javors

MA(8), de Magalhães JP(9), Martinez PA(1,)(2), McCord JM(10), Miller BF(6),

Müller M(11), Nelson JF(12), Ndukum J(5), Rainger GE(13), Richardson A(14,)(15),

Sabatini DM(16,)(17,)(18,)(19,)(20), Salmon AB(21), Simpkins JW(22), Steegenga

WT(23), Nadon NL(24), Harrison DE(5).

 

Author information:

(1)Geriatric Research, Education and Clinical Center and Research Service, South

Texas Veterans Health Care System, Department of Pharmacology, The University of

Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.

(2)Barshop Institute for Longevity and Aging Studies, The University of Texas

Health Science Center at San Antonio, San Antonio, TX, 78229, USA. (3)Department

of Pathology and Geriatrics Center, University of Michigan, Ann Arbor, MI,

48109-2200, USA. (4)Max Planck Institute for Biology of Ageing, Cologne, D-50931,

Germany. (5)The Jackson Laboratory, Bar Harbor, ME, 04609, USA. (6)Colorado State

University, Fort Collins, CO, 80523, USA. (7)Department of Medicine, University

of Wisconsin-Madison, Madison, WI, 53705, USA. (8)Department of Psychiatry,

University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229,

USA. (9)School of Biological Sciences, University of Liverpool, Crown Street,

Liverpool, L69 7ZB, UK. (10)Division of Pulmonary Sciences and Critical Care

Medicine, University of Colorado, Aurora, CO, USA. (11)Norwich Medical School,

University of East Anglia, Norwich, UK. (12)Department of Physiology and Barshop

Center for Longevity and Aging Studies, The University of Texas Health Science

Center at San Antonio, San Antonio, TX, 78229, USA. (13)Centre for Cardiovascular

Sciences, School of Clinical and Experimental Medicine, The Medical School, The

University of Birmingham, Birmingham, UK. (14)Department of Geriatric Medicine,

University of Oklahoma Health Science Center, Oklahoma City, OK, 73104, USA.

(15)VA Medical Center, Oklahoma City, OK, 73104, USA. (16)Whitehead Institute for

Biomedical Research, Cambridge, MA, 02142, USA. (17)Department of Biology, MIT,

Cambridge, MA, 02139, USA. (18)Howard Hughes Medical Institute, MIT, Cambridge,

MA, 02139, USA. (19)Broad Institute of Harvard and MIT, Seven Cambridge Center,

Cambridge, MA, 02142, USA. (20)The David H. Koch Institute for Integrative Cancer

Research at MIT, Cambridge, MA, 02139, USA. (21)Department of Molecular Medicine

and Barshop Institute for Longevity and Aging Studies, The University of Texas

Health Science Center at San Antonio, San Antonio, TX, 78229, USA. (22)Center for

Basic & Translational Stroke Research, West Virginia University, Morgantown, WV,

26506, USA. (23)Division of Human Nutrition, Wageningen University and Research

Centre, Wageningen, The Netherlands. (24)Division of Aging Biology, National

Institute on Aging, Bethesda, MD, 20892, USA.

 

The National Institute on Aging Interventions Testing Program (ITP) evaluates

agents hypothesized to increase healthy lifespan in genetically heterogeneous

mice. Each compound is tested in parallel at three sites, and all results are

published. We report the effects of lifelong treatment of mice with four agents

not previously tested: Protandim, fish oil, ursodeoxycholic acid (UDCA) and

metformin - the latter with and without rapamycin, and two drugs previously

examined: 17-α-estradiol and nordihydroguaiaretic acid (NDGA), at doses greater

and less than used previously. 17-α-estradiol at a threefold higher dose robustly

extended both median and maximal lifespan, but still only in males. The

male-specific extension of median lifespan by NDGA was replicated at the original

dose, and using doses threefold lower and higher. The effects of NDGA were dose

dependent and male specific but without an effect on maximal lifespan. Protandim,

a mixture of botanical extracts that activate Nrf2, extended median lifespan in

males only. Metformin alone, at a dose of 0.1% in the diet, did not significantly

extend lifespan. Metformin (0.1%) combined with rapamycin (14 ppm) robustly

extended lifespan, suggestive of an added benefit, based on historical comparison

with earlier studies of rapamycin given alone. The α-glucosidase inhibitor,

acarbose, at a concentration previously tested (1000 ppm), significantly

increased median longevity in males and 90th percentile lifespan in both sexes,

even when treatment was started at 16 months. Neither fish oil nor UDCA extended

lifespan. These results underscore the reproducibility of ITP longevity studies

and illustrate the importance of identifying optimal doses in lifespan studies.

 

© 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley

& Sons Ltd.

 

DOI: 10.1111/acel.12496

PMID: 27312235 [PubMed - as supplied by publisher]

 

http://www.ncbi.nlm.nih.gov/pubmed/27312235

http://onlinelibrary.wiley.com/doi/10.1111/acel.12496/full

Edited by Brett Black

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"The α-glucosidase inhibitor, acarbose, at a concentration previously tested (1000 ppm), significantly increased median longevity in males and 90th percentile lifespan in both sexes, even when treatment was started at 16 months."

 

Acarbose blocks the digestion of complex carbohydrates.  Perhaps this is more evidence that in older age it is beneficial to rebalance the diet decreasing carbohydrates and inreasing fat.

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