Abstract
Introduction: An aging population will bring a pressing challenge for the healthcare system. Insights into promoting healthy longevity can be gained by quantifying the biological aging process and understanding the roles of modifiable lifestyle and environmental factors, and chronic disease conditions. Methods: We developed a biological age (BioAge) index by applying multiple state-of-art machine learning models based on easily accessible blood test data from the Canadian Longitudinal Study of Aging (CLSA). The BioAge gap, which is the difference between BioAge index and chronological age, was used to quantify the differential aging, i.e., the difference between biological and chronological age, of the CLSA participants. We further investigated the associations between the BioAge gap and lifestyle, environmental factors, and current and future health conditions. Results: BioAge gap had strong associations with existing adverse health conditions (e.g., cancers, cardiovascular diseases, diabetes, and kidney diseases) and future disease onset (e.g., Parkinson’s disease, diabetes, and kidney diseases). We identified that frequent consumption of processed meat, pork, beef, and chicken, poor outcomes in nutritional risk screening, cigarette smoking, exposure to passive smoking are associated with positive BioAge gap (“older” BioAge than expected). We also identified several modifiable factors, including eating fruits, legumes, vegetables, related to negative BioAge gap (“younger” BioAge than expected). Conclusions: Our study shows that a BioAge index based on easily accessible blood tests has the potential to quantify the differential biological aging process that can be associated with current and future adverse health events. The identified risk and protective factors for differential aging indicated by BioAge gap are informative for future research and guidelines to promote healthy longevity.
Journal Section:
Clinical Section: Research Article
References
1.
United States Census Bureau
; He
W
, Goodkind
D
, Kowal
P
. An aging world: 2015
. Census Bureau
; 2016
.2.
3.
Galkin
F
, Mamoshina
P
, Aliper
A
, de Magalhães
JP
, Gladyshev
VN
, Zhavoronkov
A
. Biohorology and biomarkers of aging: current state-of-the-art, challenges and opportunities
. Ageing Res Rev
. 2020
;60
:101050
. 4.
Horvath
S
. DNA methylation age of human tissues and cell types
. Genome Biol
. 2013
;14
(10
):R115
. 5.
Earls
JC
, Rappaport
N
, Heath
L
, Wilmanski
T
, Magis
AT
, Schork
NJ
, et al. Multi-omic biological age estimation and its correlation with wellness and disease phenotypes: a longitudinal study of 3,558 individuals
. J Gerontol A Biol Sci Med Sci
. 2019 Nov 13
;74
(Suppl_1
):S52
–S60
. 6.
Skirbekk
VF
, Staudinger
UM
, Cohen
JE
. How to measure population aging? The answer is less than obvious: a review
. Gerontology
. 2019
;65
(2
):136
–44
. 7.
Ng
TP
, Zhong
X
, Gao
Q
, Gwee
X
, Chua
DQL
, Larbi
A
. Socio-environmental, lifestyle, behavioural, and psychological determinants of biological ageing: the Singapore longitudinal ageing study
. Gerontology
. 2020
;66
(6
):603
–13
. 8.
Putin
E
, Mamoshina
P
, Aliper
A
, Korzinkin
M
, Moskalev
A
, Kolosov
A
, et al. Deep biomarkers of human aging: Application of deep neural networks to biomarker development
. Aging
. 2016
;8
(5
):1021
–33
. 9.
Mamoshina
P
, Kochetov
K
, Cortese
F
, Kovalchuk
A
, Aliper
A
, Putin
E
, et al. Blood biochemistry analysis to detect smoking status and quantify accelerated aging in smokers
. Sci Rep
. 2019
;9
(1
):142
. 10.
Raina
PS
, Kirkland
SA
, Wolfson
C
, Szala-Meneok
K
, Griffith
LE
, Keshavarz
H
, et al. Accessing health care utilization databases for health research: a Canadian longitudinal study on aging feasibility study
. Can J Aging
. 2009
;28
(3
):287
–94
. 11.
de Lange
AMG
, Cole
JH
. Commentary: correction procedures in brain-age prediction
. Neuroimage Clin
. 2020
;26
:102229
. 12.
Gao
X
, Zhang
Y
, Breitling
LP
, Brenner
H
. Relationship of tobacco smoking and smoking-related DNA methylation with epigenetic age acceleration
. Oncotarget
. 2016
;7
(30
):46878
–89
. 13.
Carrard
G
, Dieu
M
, Raes
M
, Toussaint
O
, Friguet
B
. Impact of ageing on proteasome structure and function in human lymphocytes
. Int J Biochem Cell Biol
. 2003
;35
(5
):728
–39
. 14.
Kubota
K
, Shirakura
T
, Orui
T
, Muratani
M
, Maki
T
, Tamura
J
, et al. Changes in the blood cell counts with aging
. Jpn J Geriat
. 1991
;28
(4
):509
–14
. 15.
Dong
MH
, Bettencourt
R
, Barrett-Connor
E
, Loomba
R
. Alanine aminotransferase decreases with age: the Rancho Bernardo study
. PLoS One
. 2010
;5
(12
):e14254
. 16.
Casale
G
, Bonora
C
, Migliavacca
A
, Zurita
IE
, de Nicola
P
. Serum ferritin and ageing
. Age Ageing
. 1981
;10
(2
):119
–22
. 17.
Schöttker
B
, Hagen
L
, Zhang
Y
, Gaò
X
, Holleczek
B
, Gao
X
, et al. Serum 25-hydroxyvitamin D levels as an aging marker: strong associations with age and all-cause mortality independent from telomere length, epigenetic age acceleration, and 8-isoprostane levels
. J Gerontol A Biol Sci Med Sci
. 2019
;74
(1
):121
–8
. 18.
Steptoe
A
, Zaninotto
P
. Lower socioeconomic status and the acceleration of aging: an outcome-wide analysis
. Proc Natl Acad Sci U S A
. 2020
;117
(26
):14911
–7
. 19.
Pani
LN
, Korenda
L
, Meigs
JB
, Driver
C
, Chamany
S
, Fox
CS
, et al. Effect of aging on A1C levels in individuals without diabetes: evidence from the framingham offspring study and the national health and nutrition examination survey 2001-2004
. Diabetes Care
. 2008
;31
(10
):1991
–6
. 20.
Ericsson
S
, Berglund
L
, Frostegård
J
, Einarsson
K
, Angelin
B
. The influence of age on low density lipoprotein metabolism: effects of cholestyramine treatment in young and old healthy male subjects
. J Intern Med
. 1997
;242
(4
):329
–37
. 21.
Roetker
NS
, Pankow
JS
, Bressler
J
, Morrison
AC
, Boerwinkle
E
. Prospective study of epigenetic age acceleration and incidence of cardiovascular disease outcomes in the ARIC study (Atherosclerosis Risk in Communities)
. Circ Genom Precis Med
. 2018
;11
(3
):e001937
. 22.
Muhandiramge
J
, Orchard
S
, Haydon
A
, Zalcberg
J
. The acceleration of ageing in older patients with cancer
. J Geriatr Oncol
. 2021
;12
(3
):343
–51
. 23.
Kooman
JP
, Kotanko
P
, Schols
AMWJ
, Shiels
PG
, Stenvinkel
P
. Chronic kidney disease and premature ageing
. Nat Rev Nephrol
. 2014
;10
(12
):732
–42
. 24.
Monickaraj
F
, Aravind
S
, Gokulakrishnan
K
, Sathishkumar
C
, Prabu
P
, Prabu
D
, et al. Accelerated aging as evidenced by increased telomere shortening and mitochondrial DNA depletion in patients with type 2 diabetes
. Mol Cell Biochem
. 2012
;365
(1–2
):343
–50
. 25.
Gesing
A
, Lewiński
A
, Karbownik-Lewińska
M
. The thyroid gland and the process of aging: what is new
. Thyroid Res
. 2012
;5
(1
):16
. 26.
MacNee
W
. Is chronic obstructive pulmonary disease an accelerated aging disease
. Ann Am Thorac Soc
. 2016
;13
(Suppl 5
):S429
–37
. 27.
Li
T
, Le
W
. Biomarkers for Parkinson’s disease: how good are they
. Neurosci Bull
. 2020
;36
(2
):183
–94
. 28.
Collier
TJ
, Kanaan
NM
, Kordower
JH
. Ageing as a primary risk factor for Parkinson’s disease: evidence from studies of non-human primates
. Nat Rev Neurosci
. 2011
;12
(6
):359
–66
. 29.
Horvath
S
, Erhart
W
, Brosch
M
, Ammerpohl
O
, von Schönfels
W
, Ahrens
M
, et al. Obesity accelerates epigenetic aging of human liver
. Proc Natl Acad Sci U S A
. 2014
;111
(43
):15538
–43
. 30.
Levine
M
, Crimmins
E
. Not all smokers die young: a model for hidden heterogeneity within the human population
. PLoS One
. 2014
;9
(2
):e87403
. 31.
UDSA
. Phillips
JA
. Dietary guidelines for Americans, 2020-2025
. Workplace Health Saf
. 2021 Aug
;69
(8
):395
. 32.
McPhee
JS
, French
DP
, Jackson
D
, Nazroo
J
, Pendleton
N
, Degens
H
. Physical activity in older age: perspectives for healthy ageing and frailty
. Biogerontology
. 2016
;17
(3
):567
–80
. 33.
Rutledge
J
, Oh
H
, Wyss-Coray
T
. Measuring biological age using omics data
. Nat Rev Genet
. 2022
;23
:715
–27
. 34.
Shatenstein
B
, Payette
H
. Evaluation of the relative validityof the Short Diet Questionnaire for assessing usual consumptionfrequencies of selected nutrients and foods
. Nutrients
. 2015 Aug 4
;7
(8
):6362
–74
. 35.
Linli
Z
, Feng
J
, Zhao
W
, Guo
S
. Associations between smoking and accelerated brain ageing
. Prog Neuropsychopharmacol Biol Psychiatry
. 2022 Mar 8
;113
:110471
. 36.
Raina
P
, Wolfson
C
, Kirkland
SA
, Griffith
LE
, Oremus
M
, Patterson
C
, Tuokko
H
, Penning
M
, Balion
CM
, Hogan
D
, Wister
A
, Payette
H
, Shannon
H
, Brazil
K
. The Canadian Longitudinal Study on Aging (CLSA)
. Can J Aging
. 2009
;28
(3
):221
–9
.37.
Raina
P
, Wolfson
C
, Kirkland
S
, Griffith
LE
, Balion
C
, Cossette
B
, Dionne
I
, Hofer
S
, Hogan
D
, van den Heuvel
ER
, Liu-Ambrose
T
, Menec
V
, Mugford
G
, Patterson
C
, Payette
H
, Richards
B
, Shannon
H
, Sheets
D
, Taler
V
, Thompson
M
, Tuokko
H
, Wister
A
, Wu
C
, Young
L
. Cohort profile: The Canadian Longitudinal Study on Aging (CLSA)
. Int J Epidemiol
. 2019
;48
(6
):1752
–3j
.© 2024 S. Karger AG, Basel
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
2023
You do not currently have access to this content.
