Caloric Restriction Intervention Alters Specific Circulating Biomarkers of the Senescence-Associated Secretome in Middle-Aged and Older Adults With Obesity and Prediabetes in an 18-Week Randomized Controlled Trial.

Autor:	Justice JN; Sticht Center for Healthy Aging and Alzheimer's Prevention, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.; Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA., Leng XI; Sticht Center for Healthy Aging and Alzheimer's Prevention, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.; Department of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA., LeBrasseur NK; Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, Minnesota, USA.; Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, Minnesota, USA., Tchkonia T; Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, Minnesota, USA.; Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minnesota, USA., Kirkland JL; Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.; Division of General Internal Medicine, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA., Mitin N; Sapere Bio, Triangle Research Park, North Carolina, USA., Liu Y; Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA., Kritchevsky SB; Sticht Center for Healthy Aging and Alzheimer's Prevention, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.; Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA., Nicklas BJ; Sticht Center for Healthy Aging and Alzheimer's Prevention, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.; Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA., Ding J; Sticht Center for Healthy Aging and Alzheimer's Prevention, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.; Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Jazyk:	angličtina
Zdroj:	The journals of gerontology. Series A, Biological sciences and medical sciences [J Gerontol A Biol Sci Med Sci] 2024 Jan 01; Vol. 79 (1).
DOI:	10.1093/gerona/glad214
Abstrakt:	Cellular senescence is a biological aging process that is exacerbated by obesity and leads to inflammation and age- and obesogenic-driven chronic diseases including type 2 diabetes. Caloric restriction (CR) may improve metabolic function in part by reducing cellular senescence and the pro-inflammatory senescence-associated phenotype (SASP). We conducted an ancillary investigation of an 18-week randomized controlled trial (RCT) of CR (n = 31) or Control (n = 27) in 58 middle-aged/older adults (57.6 ± 5.8 years; 75% Women) with obesity and prediabetes. We measured mRNA expression of select senescence and apoptosis genes in blood CD3 + T cells (qRT-PCR) and a panel of 25 plasma SASP proteins (Luminex/multiplex; ELISA). Participants randomized to CR lost -10.8 ± 0.9 kg (-11.3% ± 5.4%) over 18 weeks compared with +0.5 ± 0.9 kg (+0.03% ± 3.5%) in Control group. T-cell expression of senescence biomarkers, p16INK4a and p21CIP1/WAF1, and apoptosis markers, BCL2L1 and BAK1, was not different between CR and Control groups in age, race, and sex-adjusted mixed models (p > .05, all). Iterative principal axis factor analysis was used to develop composite SASP Factors, and the Factors comprising TNFRI, TNFRII, uPAR, MMP1, GDF15, OPN, Fas, and MPO were significantly altered with CR intervention (age, sex, race-adjusted mixed model time × treatment F = 4.17, p ≤ .05) and associated with the degree of weight loss (R2 = 0.12, p ≤ .05). Our study provides evidence from an RCT that specific circulating biomarkers of senescent cell burden are changed by CR in middle-aged and older adults with obesity and prediabetes. Future studies compare tissue and circulating levels of p16INK4a and pro-inflammatory SASP biomarkers in other populations, and interventions. (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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