Aging Biomarkers: From Functional Tests to Multi-Omics

Ksenia S. Kudryashova, Ksenia Burka, Anton Y. Kulaga, Nataliya S. Vorobyeva,* and Brian K. Kennedy*

the same chronological age can vary sig

nificantly. Given that aging is the largest risk factor for a number of chronic dis

eases and also the major cause of func

tional decline, it is imperative to develop ways to measure the rate at which a given individual is aging. An effective measure of biological age could be used to pre

dict a variety of health outcomes, such as physical and cognitive function, morbid

ity, and mortality. If biological aging can be monitored, medical interventions can be applied before the first clinical symp

toms or onset of chronic diseases. The latter is especially important, because the majority of aging

related diseases have long latent periods that precede

results in various deleterious changes in the human body that may loss of function and the manifestation of chronic diseases. While diseases generally be reliably diagnosed, the aging process itself requires more approaches to evaluate its progression. Numerous attempts been made to establish biomarkers to quantify human aging at the tissue, and organismal level. Here, an up

to

date overview of related to human aging with an emphasis on biomarkers that account different mechanisms of aging between individuals is provided. discrete molecular and non

molecular biomarkers handpicked by on the base of their strong correlation with age, as well as omics

based biomarkers, are discussed and potential future and developments in the field of aging assessment are outlined.

Aging results in various deleterious changes in the human body that may lead to loss of function and the manifestation of chronic diseases. While diseases can generally be reliably diagnosed, the aging process itself requires more sophisticated approaches to evaluate its progression. Numerous attempts have been made to establish biomarkers to quantify human aging at the cellular, tissue, and organismal level. Here, an up-to-date overview of biomarkers related to human aging with an emphasis on biomarkers that take into account different mechanisms of aging between individuals is provided. Classical discrete molecular and non-molecular biomarkers handpicked by researches on the base of their strong correlation with age, as well as emerging omics-based biomarkers, are discussed and potential future directions and developments in the field of aging assessment are outlined.

1. Introduction

manifestation, in contrast to the narrow post-manifestation windows for effective treatment.[1]

Aging is a continuous natural and multifactorial phenomenon characterized by the accumulation of degenerative processes that are, in turn, underpinned by multiple alterations and damage within molecular pathways, leading to systemic pathologies of the organism. The process of aging is heterogeneous among individuals—the physical and cognitive condition of people of

Extensive effort has been directed toward the development of aging biomarkers that can determine biological age and reveal novel molecular targets for anti-aging interventions. Historically, biomarkers of aging were selected on the basis of their strong correlation with age, regardless of disease burden and do not re- port on the specific mechanisms of aging that affect each indi- vidual. Functional studies, performed primarily in animal mod- els, provide us with very precise molecular and cellular biomark- ers linked to particular driving mechanisms of aging. However, these biomarkers are often impractical for clinical use. One ma- jor and recent trend in the field of aging is the development of omics-based biomarkers that have greater potential for assessing multifactorial processes. In this review, we summarize data on all existing groups of biomarkers and biomarker-based age pre- dictors (as other reviews have done in refs. [2, 3, 4–9]), but with a focus on up-and-coming omics-based biomarkers, and outline our vision for aging assessment moving forward.

K. S. Kudryashova, K. Burka, A. Y. Kulaga, N. S. Vorobyeva AG 10, Zurich 8002, Switzerland natalia@centaura.com Y. Kulaga Biology of Aging Group of Biochemistry of the Romanian Academy Independentei 296, Bucharest 060031, Romania B. K. Kennedy of Biochemistry and Physiology Loo Lin School of Medicine University of Singapore Medical Drive, MD7, 117596, Singapore bkennedy@nus.edu.sg B. K. Kennedy Institute for Clinical Sciences (SICS) for Science and Technology (A*STAR) Centre for Molecular Medicine Medical Drive, Singapore 117609, Singapore B. K. Kennedy Institute for Research on Aging Redwood Blvd., Novato, CA 94945-1400, USA

2. Molecular and Cellular Biomarkers

The accumulation of damage at all levels of biological orga- nization is widely considered to be a primary cause of aging. Given the chemical foundation of life, first-order deleterious events arise at the level of cellular molecules.[10] The number of molecules with altered structure and function grows over time and contributes to the progressive disorder of a system, up to cell dysfunction or death. Several parameters at the molecular and cellular levels are widely proposed to be linked to aging,

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