Extending Human Life and Promoting Active Longevity

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Studies of molecular mechanisms of longevity make it possible to explore the potential for a significant increase in life expectancy, including active longevity, when older people maintain their ability to work and sustain social connections. Maxim Shkurnikov, Head of the Laboratory for Research on Molecular Mechanisms of Longevity, spoke with the HSE News Service about the laboratory’s work.

— When was this laboratory established at the university?

— The laboratory was founded in 2022 at the HSE Faculty of Biology and Biotechnology after winning a major competitive selection process. Significant efforts were made to equip it for high-performance analysis of microRNA expression, DNA sequencing, and the measurement of exosome number and size. In parallel with equipping the laboratory, the research team was assembled. We succeeded in attracting leading specialists from Moscow State University, the Engelhardt Institute of Molecular Biology (EIMB), and the National Medical Research Radiological Centre. Within less than a year, the equipment was purchased, installed, and put into operation, and the team began publishing in high-ranking journals, such as Trends in Biochemical Sciences and Nucleic Acids Research.

— What are the laboratory's main areas of focus?

— Our laboratory does not aim to directly prolong human life. Instead, we focus on studying aging processes, starting at the cellular level and extending across different organs, since the cells of the immune system, brain, heart, blood vessels, intestines, and respiratory organs function and age in distinct ways. We develop models that allow us to culture cells from different organs together and monitor their aging. The main goal is to understand the mechanisms that drive a cell to complete its life cycle. In addition, we study the early signs of diseases and work in the field of preventive medicine—for example, by examining fatty liver disease at preclinical stages, before any symptoms appear. Currently, a large interdisciplinary project is underway that aims to predict the risk of cardiovascular diseases using standard biochemical blood tests routinely performed in clinics. This complex work brings together cell biology, clinical diagnostics, and prevention of age-related diseases.

Maxim Shkurnikov

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— What does this help detect?

— Elevated levels of certain blood lipids, particularly specific fractions of low-density lipoproteins such as lipoprotein (a), are associated with a high risk of atherosclerosis and other cardiovascular pathologies.

New drugs are now emerging that make it possible to control the levels of these lipids. However, in order to prescribe them, it is necessary to know whether an individual has elevated lipoprotein (a) levels. According to current research, though, less than 0.5% of the population has ever been tested for lipoprotein (a). The insufficient detection of individuals with elevated levels poses a serious societal problem. We are working to predict these levels using data from routine biochemical bloodwork, which will make it possible to identify those who require further evaluation without the need for additional tests.

— One of your key research areas is the study of molecular mechanisms of longevity. How realistic are the prospects for a significant increase in human life expectancy?

— While this is not our primary focus, there are certainly promising prospects for extending life expectancy. Preventive medicine is advancing, making it possible to prevent the onset and progression of many diseases. Transplantology is also evolving, including xenotransplantation—the transplantation of organs from animals. These organs can be modified so that the human immune system does not reject them.

— Are predictions that humans will live to 120 or beyond in the coming decades justified?

— A radical increase in average life expectancy to 120 years or more within a single generation is unlikely, as the current average life expectancy for Caucasians is around 80–85 years. An increase of one and a half times in such a short period seems unrealistic, but extending life expectancy, including the period of active longevity, by 10–15 years is entirely feasible.

— How can this be achieved?

— The main strategies for extending life involve preventing muscle loss, slowing age-related changes in the brain, and, where possible, replacing organs. The brain, however, cannot yet be replaced, and its deterioration by the age of 80–90 remains a major challenge to longevity.

Aging in the human body has a strong genetic component. One key reason is the weak force of natural selection on traits that appear after 50–60 years, since detrimental traits rarely manifest by reproductive age (25–40 years), and longevity has historically been largely unselected by nature. However, with the average age of reproduction increasing, this situation is beginning to change.

— To what extent is it changing, and what does this mean for medicine and society?

— Modern reproductive technologies allow women to give birth to healthy children even after the age of 50. This creates the challenge of maintaining health for an additional 20–25 years to raise their offspring.

And while a rise in average life expectancy to 120 years in the coming decades seems unlikely, significantly extending the period of healthy, active life and gradually increasing the maximum lifespan are realistic goals for medicine and science.

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— There are concerns that further increases in life expectancy could lead to even more pronounced aging of the global population. Is it possible to extend healthy life proportionally?

— Of course, the length of an active and healthy life can increase proportionally with overall life expectancy. Even today, people remain capable and active much longer than in the past. For example, the retirement age was once 55 for women and 60 for men, but it is now gradually rising and is likely to continue increasing.

The key issue here is the economy and the social structure of society. For older people to remain in the workforce, workplaces must be adapted and conditions created that match their qualifications and abilities. Such measures can effectively extend active longevity and help maintain a high quality of life in old age.

— Another area of interest is the development of 2D and 3D models of human organs. How much progress has been made in this field?

— This is indeed a fascinating and highly relevant topic. For a long time, cellular models were primarily two-dimensional, with cells interacting only with others of their kind on a flat surface. In the body, however, interactions occur in all directions. That is why, over the past 20 years, three-dimensional models—where cells grow as spheroids or amorphous structures within a gel—have been actively developed. In these systems, cells interact not only with different cell types, reflecting the heterogeneity of organs, but also with the extracellular matrix. This approach allows for much more accurate modelling of organ function, and it is precisely these models that we use.

In our laboratory, we grow tumour cells together with immune cells and fibroblasts, the cells of connective tissue. This significantly alters their behaviour, allowing them to more naturally replicate processes that occur in human organs. This method is particularly valuable for selecting personalised chemotherapy treatments. When tumour cells are examined in isolation, they appear more sensitive to drugs. However, in the presence of organ cells and fibroblasts, their sensitivity decreases, better reflecting the actual clinical reality. This allows for a more accurate and informed selection of treatment regimens.

— Your laboratory and colleagues are actively studying the characteristics of COVID-19, its variants, and its progression in patients with various chronic diseases. Which ones would you highlight?

— We have investigated whether there is a genetic predisposition to severe COVID19. One of the key factors is the human major histocompatibility complex, initially identified in the context of organ transplantation. This complex triggers an immune rejection response when a transplanted organ is recognised as foreign. It also plays a crucial role when the body encounters viruses.

For each individual, the set of molecules in this complex is largely unique. It consists of six lock-like receptor variants, with the virus acting as a key. If the key fits a lock, the immune system is activated in time, and the disease progresses more mildly. If the key does not match the lock, the immune response is weaker, and the disease is more severe. This knowledge was particularly important at the beginning of the pandemic, when no standardised treatment protocols existed and outcomes largely depended on individual patient characteristics. Later, as effective treatment regimens were developed, the significance of such predictions diminished.

Another area of our work has a rather enigmatic title: 'Development of approaches for the artificial induction of aging in individual cellular models within a microfluidic system to study the interactions between aging processes in different body systems.' Simply put, we are investigating whether the aging of some cells can trigger aging in neighbouring cells. To study this, we artificially age certain cells in the model and observe whether their condition affects the behaviour of the other cells around them. This approach allows us to explore the mechanisms of coordinated aging, bringing us closer to understanding how aging progresses in the body as a whole.

— Do the cells of some organs age faster than others?

— Cells from different organs generally age at a similar rate. Moreover, they actively interact with one another, so pathological changes or damage in one organ can affect the condition of others. Typically, there are no major imbalances in the rates of organ aging.

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— What significant achievements of the laboratory would you highlight in particular?

— I would like to emphasise not only the work of our laboratory but also the major accomplishments of the entire Faculty of Biology and Biotechnology, with which we collaborate closely.

First, we have published an extensive series of studies on COVID-19 and the genetic factors that influence the course of the disease. This work has helped improve our understanding of individual differences in the body’s response to infection.

Second, we have made significant advances in the field of microfluidic models. These technologies allow us to observe cellular processes under conditions that closely mimic those in the human body.

An important area of focus has been the development of a technique for isolating primary tumour cell cultures, opening new opportunities for personalised treatment of prostate and rectal cancers.

I would like to specifically highlight our projects involving AI. We are applying machine learning methods for early diagnosis of tongue cancer. Similar to how melanomas are currently diagnosed and moles monitored, we are developing systems to detect suspicious changes in the tongue. Even a small ulcer can signal a tumour process, making timely identification critically important. To address this, we are developing a mobile application that allows a person to take a photo of their tongue. A neural network then analyses the image and, if necessary, recommends consulting an oncologist.

Another important area of our work is the application of machine learning methods to study lipoprotein (a), which plays a crucial role in cardiology and the prevention of cardiovascular diseases.

— How are the laboratory’s scientific and practical achievements integrated into the educational process? How actively do HSE University’s senior students and doctoral students participate in your work as junior staff?

— We actively involve students beginning in the second or third year of their bachelor’s programme, inviting them to join us as research assistants. This gives them the opportunity not only to conduct experiments and analyse data but also to co-author scientific publications.

Our laboratory staff also lead practical classes for students. During these sessions, we identify those who demonstrate a strong interest in research and offer them opportunities for deeper involvement in scientific activities. This helps them enter the profession early and feel like part of the scientific community.

— Which subdivisions of HSE University do you collaborate with most actively?

— Primarily with the Faculty of Computer Science, especially in the areas of machine learning and AI.

In the second half of 2021, HSE University held a competition for projects to create experimental research laboratories in the natural sciences, running from February 1, 2022, to December 31, 2026. The competition aimed to create, support, and develop scientific fields and international-level research schools, as well as to advance modern infrastructure in the university’s natural science cluster. The competition focused on two priority topics; 'Biophotonics' and 'Aging: Biology, Physiology, Biomedicine, Biostatistics, Bioinformatics.'

The results were announced in December 2021 at a meeting of the Competition Commission chaired by HSE Rector Nikita Anisimov. The winner of the competition was the project ‘The Role of Non-Coding RNA in Facilitating Active Ageing’ led by Maxim Shkurnikov, Associate Professor of the HSE Faculty of Biology and Biotechnology. With life expectancy increasing—having risen by eight years in Russia since 2000—this project is important for advancing scientific knowledge of the aging process, promoting a high quality of life, and supporting healthy aging.