Longevity & Rejuvenation

The novel Lifespinners makes a distinction between longevity and radical life extension, with the older residents of Wellowfern finding themselves on the cusp between the two. Longevity is incremental and refers to an unusually long life, while radical life extension tends to the exponential and involves big leaps in lifespan enabled by unprecedented technological and biomedical advances.

The world’s human population is ageing, although very unevenly. Global life expectancy at birth is 73.4 years (females 76, males 70.8). This compares with just under 50 years in the mid-1950s. The countries with highest life expectancy are Japan (85.03), Switzerland (84.25), Singapore (84.07), Italy (84.01) and Spain (83.99) (Worldometer, UN estimates). Unsurprisingly, there is a firm correlation between lifespan and national income. The oldest known living person is now a Japanese woman, Tomiko Itooka, age 116, and the oldest known man is Joao Marinho Neto from Brazil, age 112. The current record lifespan was set by a French woman who died at age 122 in 1997, while the record for men was set by a Japanese man who died at 116 in 2013.

On average across the world, women live about 5% longer than men, with wide variation between countries. The sex disparity stems from a combination of genetics and multiple lifestyle factors. The germ cells that develop into eggs in females and sperm in males may play an important part, while later in life, loss of the Y chromosome in older men is linked to cardiovascular disease, with greater Y loss increasing the risk of death. Globally, the life expectancy gap has been closing in recent decades, which is thought to reflect significant lifestyle trends, including a decline in smoking and heavy drinking among men. More generally, however, there are signs that the dramatic rise in life expectancy is now slowing, despite the success of new medicines and life-saving treatments for many serious illnesses and conditions. Some genetic experts also think we may be reaching (or have now reached) a ceiling or upper age limit for human lifespan, either definitively or at least in the short term, until the next wave of scientific and medical advances arrives to overtake the ageing process.

At a local societal level, there are common elements among some communities where human lifespan is notably longer than average. Among these groups, the way of life includes a nutritious diet rich in natural food and low in meat, daily movement through walking and physical work, a strong and enduring sense of purpose, and supportive relationships within the family and neighbourhood. These features highlight the importance of external environmental influences and social connections on our bodily systems. Thoughtful building design and sensitive local planning systems also promote social contact, mutual support networks and purposeful activity, resulting in holistic solutions that can help to provide an environment conducive to boosting lifespan.

In modern societies, warding off serious illness and averting premature death often requires the ability and willingness to make healthier personal choices related to diet and nutrition, exercise, brain and body resilience, rest and sleep, type of work, stress management, oral hygiene, emotional health and general health awareness. Too many people are living longer but in poor health. Many experts in the science of ageing now emphasise the importance of healthspan, the length of time that someone lives in good health and with the opportunity to enjoy their life. At its most radical, this entails a broadly based preventative approach to health and wellbeing through middle age and a complete rethink of old age, with the expectation that many more older people will keep well and continue their active life in myriad ways: extending their career, changing jobs, starting a business, learning new skills, furthering their education, supporting their family, friends and community, inspiring their grandchildren, pursuing their creative talent or taking off in some other new direction

Researchers are exploring the links between personality, longevity and the body’s immune system. There is a growing body of evidence to indicate that an optimistic mindset and the personality trait of conscientiousness correlate with a long and healthy life. Greater optimism is associated with less inflammation, healthier lipid levels and higher antioxidants, as well as a better diet and more effective management of stressful situations. Recent research using data from multiple studies has found a strong link between measured personality traits and the risk of dementia, with a wide protective effect if people score highly on the traits of conscientiousness and extroversion. People’s social circumstances also play a part in the cycle of cause and effect, with a more positive outlook on life more likely among people who have a high standard of living and a greater range of opportunities.

Scientists have discovered a group of ‘super-agers’, whose memories are on a par with younger adults and whose brains have greater hippocampus volume and a visual cortex displaying youthful patterns. These youthful patterns in some people who have reached their nineties can extend to greater resilience against illness and higher cognitive and physical abilities, although these may be more closely associated with their favourable genetic mutations than with their personality or lifestyle.

There are also links between the body’s circadian rhythms and how individuals age. Circadian rhythms are the physical, mental and behavioural changes that follow a 24-hour cycle. They are regulated by our natural timing devices known as biological clocks, which are made up of specific molecules and located around the body. Calorie restriction and timing of eating (earlier in the day and over a shorter time period) are beneficial. Some treatments for ageing diseases are also more effective if given at specific times of day.

Medical advances, immunisation and improved daily diets, hygiene and social conditions allow people in more prosperous societies to have longer lives. They also enable us to live to an age where we may experience the effects of negative mutations in our genome. Some genetic mutations can have a positive effect in youth but a negative effect as we age. The process by which our genes switch on and off, for example to create an immune response, also becomes less effective in older age, inhibiting production of the necessary proteins. This change may result from cumulative damage to our DNA, which in turn affects many cellular activities that are vital for smooth bodily function. The result is senescence, a decline in the ability of cells to clear debris and carry out other essential tasks.

The ageing process is also influenced by the shortening of telomeres, which are protective sections of DNA capping the ends of our chromosomes. Each time a cell divides, a part of the repeating sequence in a telomere is lost. When the telomeres become too short to work effectively, a cell will die or stop dividing.

Cellular senescence is important to understanding cognitive decline in older age. The affected cells are still alive but have stopped dividing and are harmful to organ function. In the brain, they can block neuroregeneration and there is growing evidence that clearing out senescent cells with senolytic drugs may reverse some cognitive defects. For understandable reasons, people who are concerned for their health tend to prioritise physical fitness, while giving little or no attention to cellular level wellness and the need to control inflammation. Continuous low-grade inflammation is concealed until it produces symptoms indicating a heart condition, cancer or a neurodegenerative disease. A practical plan for slowing the inflammation process includes eating a variety of plant foods and nuts, playing a musical instrument, practising short bursts of high-intensity exercise and turning the shower cold for an icy rinse.

The role of the lymphatic system is also gaining more recognition as research extends our understanding of how this crucial network of nodes, vessels and fluids carries nutrients and relays chemical messages. The lymph nodes in the neck, armpit, stomach and groin act as filters, trapping or destroying toxins and attacking viruses, bacteria and cancer cells. This relies on muscle action and if it is slowed by inactivity or poor nutrition, it can result in inflammation, fatigue and joint pain. Impairment of the lymphatic vessels in the brain is linked to higher levels of amyloid-beta deposits present in Alzheimer’s disease. Suggested pro-lymph activities include: saunas and hot baths; herbs and spices; massage, humming and yoga; running, cycling or bouncing on a trampoline.

As the older population has increased in many countries, so have frailty and illness among the oldest group (although many centenarians are exceptions). The average 80-year-old has four age-related conditions and the challenge is to understand progressive changes in function and design novel interventions that delay the onset of age-related diseases. Dementia, cancer, cardiovascular disease and diabetes are among the leading health-related killers in older age. These common diseases, as well as other serious and limiting conditions such as arthritis and osteoporosis, share specific features or hallmarks of ageing.

In the past few years, great strides have been made in designing new drugs to alleviate, manage or slow the progress of previously incurable conditions. As examples, people with multiple sclerosis or at risk of heart disease now have medicinal options to prevent or modify the condition. In the near or medium term future, vaccination may become available as a treatment for the major non-infectious conditions of older age, including Alzheimer’s and cancer.

The medications already in use to treat specific health conditions are also now being tested in research into the ageing process itself. These include medicines that zone in on hallmarks of ageing, such as deteriorating stem cell function and dysfunctional mitochondria within cells. Tackling the biological causes of ageing may stop the diseases taking hold and help older people to avoid living with several life-limiting health conditions at the same time.

Dementia is an umbrella term for several conditions and affects an estimated fifty-seven million people across the world. Many of the risk factors have been identified, including at least a dozen individual and social factors that can potentially be tackled and modified, if there is the will and determination at both policy level and among communities and families. They include exposure to air pollution, diabetes, smoking, gut inflammation, hearing loss and social isolation. Another strong area of current research is early diagnosis through AI-assisted blood tests that will be able to diagnose a condition such as dementia, cancer or Parkinson’s disease several years before there are any symptoms. Success in this pioneering research and other revolutionary technologies will open the door to new screening programmes and an increasingly predictive and preventative approach.

Depending on the individual, biological age can be either higher or lower than chronological age. Intriguingly, different parts of the body also age at different rates, creating a unique set of ‘epigenetic markers’ for each individual and also revealing the variation between different organs or types of tissue. Analysis of natural changes in DNA (methylation) can also show the effects of disease, with cancerous tissue, for example, being biologically much older than the person’s chronological age. Scientists are now developing screening blood tests to check the ageing rates of different parts of the body and assess the risk for conditions such as heart failure or dementia.

Greater understanding of the intricacies and complexities of biological ageing is leading towards new ways of slowing down or reversing the ageing process. The close association between ageing and particular debilitating diseases and conditions also allows for optimism that these novel interventions will help to delay, prevent or eliminate such diseases in the near or medium term future.

In terms of medication, the drug rapamycin is one of the most promising as an anti-ageing medicine and some other medications now prescribed for specific conditions such as diabetes and obesity also appear to have wider anti-ageing effects. In addition, researchers are developing new generation drugs that can find and destroy senescent cells, which will result in a new range of ‘senolytic’ treatments. Possible future applications could include: reprogramming ageing cells, using adult stem cells that have the capacity to develop into another type of cell (pluripotency); reactivating the splicing factors in inactive cells, so that they rejuvenate and continue to divide like young cells; using courier viruses to smooth cell nuclei that wrinkle and stop DNA working properly; and replacing blood plasma with donated blood products.

Neuroscientists are adapting their view of how the brain operates throughout life. Advances in neuroimaging and results from large studies show that some cognitive abilities may improve in middle and older age. They include: ability to distil the big picture; heightened emotion perception; ability to ‘read’ other people; adaptable brain networks; tendency to accentuate the positive; and ability to select positive goals, using knowledge, expertise and emotional intelligence. These findings accord with the logical theory that crystallised intelligence, which is reliant on known facts and experiences, increases with age. Fluid intelligence, by contrast, revolves around the ability to think fast and abstractly and to solve problems without specific learning or prior experience. This fluid intelligence is more evident in the brain activity of young people.

While IQ and a certain kind of intellectual ability have been highly regarded, some of the greatest human achievements have relied primarily on qualities such as curiosity, creativity and imagination. These traits are found in what scientists call ‘cognitive flexibility’, a skill that enables us to switch between concepts or adapt behaviour in a new or changing environment. It is key to creativity and includes more rational thinking, which helps people to develop strategies to overcome their biases. It is also associated with more resilience to negative life events, as well as a better quality of life in older age and a higher ‘cognitive reserve’, which protects against later decline in brain performance. Cognitive reserve builds up over time and is bolstered by activities that require mental flexibility, agility and problem-solving skills, as well as management of stress, social connection and a balance between mental effort and relaxation.

Neuroscientists have also become interested in the highly beneficial effects of learning and listening to music. It seems that playing an instrument can help to improve memory and build up cognitive reserve. Practising music and singing, particularly with other people, activates the brain’s limbic centre and releases ‘happy’ chemicals, such as dopamine. More broadly, music engages multiple brain areas – cognitive, sensory, motor and rewards systems – in distinctly positive ways. The benefits may be especially high if you are a novice, or taking up music again after a gap.

Edited October 2024