← Back to Wiki Home

Biological Age

Biological age refers to the physiological state of an individual's body functions, distinct from their chronological age. It aims to quantify the 'wear and tear' of the body at a molecular level, offering insights into biological ageing and even predicting mortality.

Biological Age Testing

Several computational models, known as biological ageing clocks, estimate an individual's biological age by analysing biomarkers such as DNA methylation and plasma proteins. These include the Horvath, Hannum, Levine, GrimAge, and DunedinPACE clocks, each employing different biological measurements. Epigenetic biomarkers focus on changes in gene activity, offering insights into the impact of lifestyle and environmental factors on genetics and health.

The gut microbiome is a key area of biomarker research on ageing, as its composition changes with age and reflects exposomal exposures.

Biological age tests, available OTC as at-home diagnostic kits or in clinical settings, use saliva or blood samples. While some clocks quantify the rate of ageing, others analyse the exposome, the sum of environmental exposures from conception to death.

These clocks have applications in gerontology and geroscience, helping researchers develop anti-ageing interventions and study the effects of lifestyle choices on ageing. Age deceleration interventions, targeting diet, exercise, and stress management, aim to slow or reverse biological ageing as measured by these clocks.

However, these tools present challenges related to individual variability, validation, and standardisation, due to complex biological and environmental interactions.

Biological Ageing Mechanisms

Ageing is a complex biological process resulting from various mechanisms that contribute to frailty and resilience. These mechanisms interact across molecular, cellular, and systemic levels, influencing the development of age-related disorders.

Key biological ageing mechanisms include:

These processes impact the development of diseases such as neurodegeneration, cardiovascular illness, and metabolic syndromes.

The gut microbiome plays a significant role in ageing, influencing inflammatory immunity, nutrient metabolism, and neuroprotection. Changes in its composition reflect ageing, acting as a potential biomarker.

Environmental factors, including stress, significantly impact biological ageing. Chronic psychosocial stress influences cellular damage, DNA damage response, telomere maintenance, mitochondrial function, and cellular senescence.

Research fields like geroscience aim to understand ageing at a molecular level and develop interventions to prevent age-related diseases, focusing on dietary and gut microbiome interventions.

Exposome and Ageing

The exposome is a conceptual framework encompassing all external exposures an individual experiences from conception to death. This includes physical, social, and sociopolitical environments, along with personal lifestyle choices.

The exposome is a critical determinant of ageing, influencing the accumulation of molecular and cellular damage throughout life. This process is characterised by genetic, epigenetic, metabolic, and immune interactions leading to a gradual decline in cellular and physiological functions.

Key exposomal factors impacting ageing include:

The exposome's role is further demonstrated by its influence on the gut microbiome, which contributes to ageing clocks. These clocks estimate biological age using microbial taxonomy, biodiversity, and functionality.

The gut microbiome's composition changes with age, reflecting exposomal exposures, especially diet and lifestyle. Microbiome-derived metabolites and microbial exposure influence epigenetic modifications related to ageing.

Geographical location also impacts the gut microbiome and, thus, ageing, as certain regional exposures leave distinct metabolic signatures. Therefore, the exposome's complex interplay with genetic and biological mechanisms significantly impacts the ageing process.

Geroscience

Geroscience is an interdisciplinary field of study dedicated to delaying or preventing age-related diseases and decline. It focuses on the complex mechanisms of ageing, exploring the interplay between genetic, epigenetic, metabolic, immune, and environmental factors.

The primary goal is to develop interventions against age-related illnesses, targeting dietary and gut microbiome modifications, to enhance healthspan and longevity. This involves holistic approaches that encompass dietary changes, exercise, lifestyle interventions, and stress management.

Key areas of research include:

Geroscience also encompasses gerontechnology, focusing on technological solutions to aid older adults' independence and quality of life. Additionally, it informs geronmedicine – an emerging discipline integrating traditional medicine with scientific research on ageing.

Delaying and Reversing Ageing

Ageing is a complex process best characterised as the chronic dysregulation of cellular processes leading to deteriorated tissue and organ function. While ageing cannot currently be prevented, its impact on lifespan and healthspan in the elderly can potentially be minimised by interventions that aim to return these cellular processes to optimal function.

Recent studies have demonstrated that partial reprogramming using the Yamanaka factors (or a subset; OCT4, SOX2, and KLF4; OSK) can reverse age-related changes in vitro and in vivo. However, it is still unknown whether the Yamanaka factors (or a subset) are capable of extending the lifespan of aged wild type mice.

Loss of epigenetic information as a cause of mammalian ageing. All living things experience an increase in entropy, manifested as a loss of genetic and epigenetic information. In yeast, epigenetic information is lost over time due to the relocalization of chromatin-modifying proteins to DNA breaks, causing cells to lose their identity, a hallmark of yeast ageing. Using a system called "ICE" (inducible changes to the epigenome), we find that the act of faithful DNA repair advances ageing at physiological, cognitive, and molecular levels, including erosion of the epigenetic landscape, cellular exdifferentiation, senescence, and advancement of the DNA methylation clock, which can be reversed by OSK-mediated rejuvenation.