What Is Biological Age — and How Is It Different From Chronological Age?
Summary ID01-BA-RS-00015
Research Summary
Original Publication
Measuring Biological Age Using Omics Data
Journal
Nature Reviews Genetics, .
- Category
- 01Biological Age
- Evidence
- State-of-the-Art Review
- Summary Type
- Core
What Was Studied?
Chronological age tells us how much time has passed since we were born. Biological age asks a different question: how does the biological state and function of a person, organ or cell compare with what would normally be expected at that chronological age?
This distinction matters because aging is not uniform. People of the same chronological age — and even different tissues within the same person — may show different patterns and rates of biological aging.
In this review, the authors critically examined the rapidly developing science of measuring biological aging using large-scale molecular, or “omics,” data.
They placed modern aging clocks within the broader evolution of aging biomarkers — from visible signs of aging and conventional physiological measures to cellular and molecular hallmarks and, more recently, omics-based measures designed to integrate multiple molecular changes associated with aging.
The authors reviewed aging clocks developed from epigenomic, transcriptomic, proteomic and metabolomic data, together with machine-learning approaches used to combine large numbers of age-related molecular features into estimates of age.
The review traces major developments in aging-clock research, including the landmark DNA methylation clocks introduced in 2013, and examines what different generations and molecular types of clocks actually measure.
At the center of the review is an important question: do aging clocks simply predict chronological age, or can they capture meaningful differences in biological aging?
The authors also examined the biological meaning of the age gap — the difference between clock-predicted and chronological age — and considered approaches for measuring aging across cells, tissues and organs, as well as the rate of aging over time.
Key Findings
Epigenetic clocks established a new molecular approach to measuring age. DNA methylation became one of the most established foundations for molecular aging clocks. Landmark clocks published in 2013 — including Horvath’s multi-tissue clock — demonstrated that patterns of DNA methylation could estimate chronological age with considerable accuracy across human tissues and cell types.
Predicting chronological age is not the same as measuring biological aging. Many first-generation clocks were primarily trained to predict chronological age. A clock can therefore be highly accurate at estimating how many years someone has lived without necessarily capturing the biological differences that distinguish health and aging trajectories between people of the same age.
Newer clocks aim to capture health-related aspects of aging. Second-generation epigenetic clocks, including DNAm PhenoAge and DNAm GrimAge, incorporate information related to physiological characteristics, morbidity or mortality rather than chronological age alone. Such clocks can show stronger associations with mortality, cardiovascular disease, frailty and physical or cognitive decline.
Biological age can be approached through different molecular systems. The authors reviewed clocks based on epigenomic, transcriptomic, proteomic and metabolomic data. Each molecular layer provides a different window into aging biology, and no single omics approach was shown to provide a complete picture.
Different aging clocks capture different aspects of aging. Age gaps generated by different clocks frequently show only weak or modest agreement, and different clocks have different sensitivities to mortality, cognitive decline, cardiovascular disease, diabetes and physical dysfunction.
Biological aging is heterogeneous throughout the body. Different organs and tissues — including the heart, brain, immune and metabolic systems — may age to different degrees and through different mechanisms. Even different cell types within the same tissue may follow distinct aging trajectories.
Biological age and pace of aging are related but different. Most aging clocks estimate biological state at one point in time. Longitudinal approaches instead attempt to measure how rapidly aging-related biological changes accumulate over time.
No single approach has emerged as the definitive measure of biological age. Aging clocks based on different molecular modalities often do not agree, and there is currently no clear reference standard against which all clocks can be evaluated.
Why It Matters for Longevity
Biological age is becoming an important concept in longevity medicine because chronological age alone cannot explain why people of the same age may differ substantially in health, function and vulnerability to age-related disease.
A central goal of longevity research is to understand whether the biological processes of aging can be measured — and potentially modified — to preserve health and function for longer. This requires reliable measures of biological age and the rate of aging.
Omics-based aging clocks offer new ways to measure molecular changes associated with aging. However, biological age should not be reduced to a single universal number. DNA methylation, gene expression, proteins and metabolites provide overlapping but distinct biological information.
This becomes particularly important when biological-age measures are used to evaluate longevity interventions. A change in an aging clock may be biologically meaningful, but it does not automatically mean that a person has become physiologically younger or that their future risk of disease has been reduced.
For longevity research, the goal is not simply to build clocks that accurately predict chronological age, but to identify biomarkers that reflect meaningful differences in biological aging and relate to healthspan, functional decline, disease and survival.
The more useful question may therefore be not only “What is my biological age?” but also “What aspect of my biological aging is this particular measurement actually capturing?”
Clinical Perspective
Biological-age measurements have potential as tools in precision and preventive medicine, but their interpretation requires caution.
A clock designed primarily to predict chronological age should not automatically be interpreted as a measure of overall health or future disease risk. Its clinical relevance depends on what it measures, how it was developed and which health or functional outcomes it has been validated against.
The findings also challenge the idea that one test can provide a definitive biological age for the entire person. Different molecular, tissue-specific and potentially longitudinal measurements may ultimately provide complementary information about how an individual is aging.
Key Takeaway
Biological age cannot currently be reduced to one universal measurement. Different aging clocks capture different molecular features and show different relationships with aging-related outcomes, while biological aging itself can vary between individuals, organs, tissues and cells. Understanding what a particular clock measures is therefore essential before interpreting its biological or clinical meaning.
Reviewed and Summarized by
Source Publication
- Title:
- Measuring Biological Age Using Omics Data
- Authors:
- Jarod Rutledge, Hamilton Oh, Tony Wyss-Coray
- Journal:
- Nature Reviews Genetics, December 2022; 23:715–727.
