Lifespan: Why We Age: What You Can Measure Today | YEARS

What is behind 'Lifespan – Why We Age – and Why We Don't Have To'?

The book Lifespan – Why We Age – and Why We Don't Have To triggered a wave that reached far beyond the niche of longevity research. The author David Sinclair is a Professor of Genetics at Harvard Medical School and has been researching the molecular mechanisms of aging for more than 25 years. His central thesis: aging should be understood as a treatable biological process and is at times explicitly described by Sinclair as a disease.

This idea, packaged in an accessible narrative by co-author Matthew LaPlante, moved the topic from laboratories to bestseller lists. Sinclair argues that we can understand the biological processes that lead to decline and disease and influence them in targeted ways. The book became a manifesto for a movement that wants to live longer, but above all to remain healthy for longer.

The hype also brought controversy. Sinclair's claims regarding supplements such as resveratrol or NMN are disputed within the scientific community or are based on animal studies whose transferability to humans has not yet been established.

A clear distinction is useful here: David Sinclair is an influential researcher, but not a practicing physician. His book is based on solid scientific foundations, but also contains hypotheses that remain at an experimental stage. This article translates his central ideas into clinical reality and shows what can already be measured in your own body today. It does not replace medical advice, but gives you the tools to ask the right questions.

The Information Theory of Aging: what does it actually mean?

To understand why aging might be treatable according to Sinclair, you need to know his central theory: the Information Theory of Aging. He uses an intuitive metaphor:

• Your DNA is the hardware. It is the digital code of your life, robust and largely stable over decades.
• Your epigenome is the software. It is the regulatory layer that tells your DNA which genes should be switched on or off in each cell. A liver cell and a skin cell have the same DNA, but their epigenome ensures that they perform their specific functions.

Sinclair's central hypothesis, known as the Information Theory of Aging, states that aging is driven to a significant extent by a progressive loss of youthful epigenetic information. Damage accumulates throughout life. DNA breaks, inflammation, and other stressors force cells to perform constant repair work, during which epigenetic regulatory patterns may lose precision. Cells may consequently lose parts of their original gene-expression and identity patterns.

This idea is supported by research showing that cells can be "reprogrammed" in the laboratory. The discovery of the Yamanaka factors, for which Shinya Yamanaka received the Nobel Prize in 2012, demonstrated that specialized body cells can be returned to a pluripotent, stem-cell-like state. Partial reprogramming remains predominantly at the preclinical research stage; robust clinical evidence for rejuvenation in humans is still lacking.

What does this mean in practice? If aging is associated with changes in epigenetic information, then some of these changes are potentially measurable. This is where the work of geneticist Steve Horvath comes in. In 2013, he showed that epigenetic patterns on our DNA change with age in predictable ways. These changes, specific DNA methylation patterns, function like a biological signature of aging and form the basis of so-called epigenetic clocks (Horvath et al., Genome Biology 2013).

Healthspan vs. Lifespan: why the distinction matters

Two central terms in the longevity discussion are regularly confused:

• Lifespan refers to the total duration of life, measured in years.
• Healthspan describes the period of life spent in good health and with a high level of functional quality of life.

The goal of modern preventive medicine is to maximize healthspan, rather than extend life at any cost. The concept is not new: Stanford Professor James Fries described it as early as 1980 as "Compression of Morbidity," meaning the compression of disease burden into the shortest possible period at the end of life (Fries, NEJM 1980).

In many industrialized countries, there is a substantial gap between lifespan and healthspan. Estimates suggest that people spend the final 8 to 10 years of their lives living with chronic diseases such as diabetes, cardiovascular disease, neurodegenerative conditions, or cancer (Garmany et al., npj Aging 2021).

When Sinclair says that most people die too early, what he primarily means is that they become ill too early and remain ill for too long. To improve healthspan, relevant health risks and functional changes first need to be measurable.

Biological age: what the number on your birthday cake does not tell you

Your chronological age tells you how many times you have travelled around the sun. Biological age, by contrast, is an umbrella term for estimates of various age-related biological characteristics that may differ from chronological age. Two 50-year-olds can therefore have very different profiles. One may have substantially better cardiovascular and metabolic health than the other.

There are several approaches to assessing age-related biological changes:

• Epigenetic clocks: They are among the most extensively studied approaches for estimating age-related biological changes based on DNA methylation patterns.
• Proteomics: Analysis of the complete set of proteins in the blood.
• Metabolic markers: Values such as blood glucose, insulin, and lipids provide information about metabolic health.
• Physiological tests: Functional assessments such as maximum oxygen uptake (VO₂max) or arterial stiffness.

Biological age is not a single absolute value. Different clocks and methods measure different aspects of aging and can produce different results. Their strength lies in combining several measurements and following trends over time. In the YEARS Ultimate® Program, epigenetic analyses are among the methods used to assess different age-related biological signatures.

Longevity biomarkers: what research currently knows

Sinclair's book and modern longevity research have brought a range of biomarkers into focus. Which of them are scientifically established and clinically measurable today?

Here is what these markers represent:

• Epigenetic clocks (Horvath Clock, PhenoAge, GrimAge): Newer clocks such as GrimAge are associated at population level with mortality and various age-related health outcomes. They analyze patterns on your DNA and provide statistical estimates of age-related biological changes. Their relevance for individual clinical decision-making, however, remains limited.
• NAD+: This molecule is central to cellular energy production. NAD+ is an important coenzyme in energy metabolism and is required by sirtuins as a cosubstrate. Clinical measurement of NAD+ levels in blood is not yet standardized. For this reason, NAD+ measurement is currently not part of YEARS diagnostics.
• Inflammatory markers (hs-CRP, IL-6): Chronic low-grade inflammatory activity plays a role in many age-related diseases. hs-CRP is an established marker of low-grade systemic inflammatory activity and cardiovascular risk stratification, but it does not specifically measure inflammaging. The JUPITER trial showed that people with elevated hs-CRP despite LDL levels below 130 mg/dL could benefit from statin therapy in terms of cardiovascular events (Ridker et al., NEJM 2008).
• Cardiovascular markers (ApoB, Lp(a)): Cardiovascular diseases are among the most common causes of death worldwide. ApoB can reflect atherogenic particle burden more precisely than LDL cholesterol, particularly when lipid values are discordant. Lp(a) is a strong, predominantly genetically determined risk factor that is not routinely included in the standard statutory health check-up.
• Metabolic markers (HOMA index, OGTT): HOMA-IR can provide indications of reduced insulin sensitivity, while an OGTT assesses glucose processing after a defined glucose load. Changes in these metabolic parameters can occur years before the manifestation of type 2 diabetes.
• Cardiorespiratory fitness: A study involving more than 120,000 people showed a strong inverse relationship between cardiorespiratory fitness and all-cause mortality. The elite-fitness group had an approximately 80% lower adjusted mortality risk compared with the lowest-fitness group (Mandsager et al., JAMA Network Open 2018).

What is clinically available today and what remains research

Clinically available or diagnostically usable today

A comprehensive diagnostic assessment that systematically captures relevant drivers of healthspan and disease risk can include the following areas today:

• Epigenetic clocks: Clinically available, but still limited in terms of individual interpretation. At YEARS, epigenetic analyses are part of the Ultimate® Program.
• Detailed biomarkers: Measurement of inflammation (hs-CRP), cardiovascular risk (ApoB, Lp(a)), and metabolic health (HOMA index).
• Functional testing: Measurement of VO₂max using cardiopulmonary exercise testing, arterial stiffness, muscle strength, and cognitive performance.
• Imaging:
• Whole-body MRI: Provides a radiation-free structural assessment and can visualize structural abnormalities including certain tumors, vascular changes, or organ abnormalities. Responsible management of so-called "incidental findings" is part of a physician-supervised setting: an unexpected finding may be clinically relevant, but can also lead to further investigations. Learn more about whole-body MRI diagnostics at YEARS.
• Cancer screening:
• Liquid Biopsy: The truCheck method used at YEARS looks for circulating tumor-associated cells in the blood rather than ctDNA fragments. The technology is undergoing active clinical development. Evidence for its use in asymptomatic individuals is still evolving; positive findings require conventional confirmation. It complements established screening but does not replace it. Learn more about Liquid Biopsy at YEARS.

Still within research or not standardized

• NAD+ measurement: No validated, clinically standardized method is currently available for routine diagnostics.
• Telomere length: Measurement in individuals is too variable to serve as a reliable standalone marker for longevity planning.
• Partial reprogramming: Remains predominantly at the preclinical research stage; robust clinical evidence for rejuvenation in humans is still lacking.

Without medical context, however, the significance of individual measurements is strongly limited. A list of biomarkers is not a plan. Only the synthesis of all findings by an experienced physician creates a meaningful, prioritized preventive strategy.

How YEARS measures relevant longevity markers

At YEARS, diagnostic programs were created around one central question: Which drivers of healthspan and longevity can already be measured and clinically interpreted today?

• YEARS Core® (€1,900 | 6 hours): Establishes a comprehensive medical baseline with 87 biomarkers, including key inflammatory (hs-CRP), cardiovascular (ApoB, Lp(a)), and metabolic markers (HOMA index, OGTT). This is complemented by VO₂max measurement, body plethysmography for lung function, bone density measurement, a 3D body scan, cognitive testing, and comprehensive ultrasound of the heart, abdomen, thyroid, and blood vessels.
• YEARS Evolve® (€7,600 | 9 hours): Builds on Core®. In addition to everything included in Core®, it includes 120+ biomarkers, whole-body MRI, Liquid Biopsy (truCheck) for cancer screening, and storage of your samples in the YEARS Biological Safe for future analyses.
• YEARS Ultimate® (€16,900 | 9 hours): The most comprehensive YEARS diagnostic program. It includes everything from Evolve® and expands the analysis to more than 230 biomarkers. Genomic analyses assess genetic variants with potential relevance to disease risk and pharmacogenetics. Epigenetic analyses and a gut microbiome analysis complete the picture.

All programs result in a YEARS Health Report of more than 60 pages and a detailed strategy consultation with a physician, during which your data is translated into a concrete, prioritized action plan for the next 12 months.

Lifespan as inspiration, diagnostics as the starting point

David Sinclair's Lifespan changed the public discussion around aging and helped establish the idea that we can actively shape our healthspan. It is not a manual; it is a useful starting point for asking the right questions.

What is clear today: Many age-related risk factors and physiological changes can already be measured before clinical symptoms arise. If you do not know your starting point, it becomes difficult to track change. A diagnostic baseline turns vague concerns into concrete data and data into an actionable plan.

Start with your personal longevity diagnostics at YEARS in Berlin.

Disclaimer: This article is intended for general informational purposes and does not replace individual medical advice. All diagnostic measures at YEARS are accompanied and interpreted by a medical team.

Sources

• Fries, J. F. (1980). Aging, Natural Death, and the Compression of Morbidity. New England Journal of Medicine, 303(3), 130–135. DOI: 10.1056/NEJM198007173030304
• Garmany, A., Yamada, S., & Campisi, J. (2021). The complex interplay between aging and cancer. npj Aging and Mechanisms of Disease, 7(1). DOI: 10.1038/s41514-021-00078-z
• Horvath, S. (2013). DNA methylation age of human tissues and cell types. Genome Biology, 14(10), R115. DOI: 10.1186/gb-2013-14-10-r115
• Mandsager, K., Harb, S., Cremer, P., Phelan, D., Nissen, S. E., & Jaber, W. (2018). Association of Cardiorespiratory Fitness With Long-term Mortality Among Adults Undergoing Exercise Treadmill Testing. JAMA Network Open, 1(6), e183605. DOI: 10.1001/jamanetworkopen.2018.3605
• Ridker, P. M., Danielson, E., Fonseca, F. A. H., Genest, J., Gotto, A. M., Kastelein, J. J. P., ... & JUPITER Study Group. (2008). Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein. New England Journal of Medicine, 359(21), 2195–2207. DOI: 10.1056/NEJMoa0807646
• Yamanaka, S. (2012). The winding path to pluripotency (Nobel Lecture). Angewandte Chemie International Edition, 52(52), 13900–13909.