Long-lived families reveal a rare genetic clue to healthy ageing; scientists say it may help explain why some people stay disease-free for years longer

Growing old is inevitable, but growing old while staying active, mentally sharp, and free from serious diseases appears to be influenced by more than luck alone.

Scientists have long observed that some families seem to age differently.

Parents live into their 90s, remain independent, and often pass those traits to their children.

Now, researchers have identified rare genetic variants that may help explain why.Presented at the annual conference of the European Society of Human Genetics in Gothenburg, the study suggests that healthy ageing may partly be inherited.

More importantly, it reinforces a message doctors have repeated for years: genes matter, but they work alongside everyday habits that shape health over decades.Life expectancy has increased dramatically across the world, but the years spent in good health have not risen at the same pace.

Scientists call these healthy years "healthspan," the period of life spent free from major diseases and cognitive decline.Researchers from Leiden University Medical Center in the Netherlands studied 212 families with exceptional longevity as part of the Leiden Longevity Study.

Instead of focusing only on individuals who lived longer, they looked at entire families to understand what biological factors may be passed down through generations.Their earlier work had already shown that middle-aged adults with long-lived parents developed cardiometabolic diseases around 13 years later than their partners whose parents had average life spans.After analysing thousands of genes, researchers narrowed their search to just 350 candidates and eventually identified 12 rare genetic variants that may contribute to healthy ageing.However, excessive or chronic inflammation is also linked to many age-related diseases, including heart disease, diabetes and dementia.Researchers found a mutation in the CGAS gene in two long-lived families.Scientists believe that a balanced inflammatory response may help protect tissues from long-term damage while preserving the body's natural defences.Doctors say the findings should not be interpreted as evidence of a single "longevity gene."Dr Suchismitha Rajamanya, Lead Consultant and Head of Internal Medicine at Aster Whitefield Hospitals, said, "The findings are an important reminder that healthy ageing is not determined by a single 'longevity gene' or miracle habit.

What we are increasingly learning from studies involving people who remain physically active, cognitively sharp, and independent well into their 90s is that successful ageing is usually the result of several protective factors working together over decades.

These include decent heart circulation health, steady physical activity, shunning smoking, social connectedness, and keeping mental resilience together with it a bit."She added that many healthy adults in their 90s are not necessarily free from age-related biological changes."One particularly interesting observation across longevity research is that many older adults who remain healthy in their 90s are not necessarily free from age-related biological changes.

Instead, they appear to possess a greater ability to withstand or compensate for those changes.

Researchers often describe this as resilience rather than simply the absence of disease."In other words, ageing successfully may depend less on avoiding every health challenge and more on developing the ability to adapt and recover.Genes can provide a foundation, but lifestyle choices continue to play a major role.Dr Rajamanya explained, "From a medical perspective, the message is encouraging because many of the factors associated with healthy ageing are modifiable.

Physical activity remains one of the strongest predictors of maintaining mobility, independence, and quality of life in later years.

Studies have shown that exercise habits adopted even decades earlier can influence health outcomes after the age of 90."The scientists caution that the findings are still at an early stage.

Completely blocking the CGAS pathway could have harmful effects, including increased susceptibility to infections and certain cancers.

To better understand how the mutation works, researchers are planning experiments using killifish, one of the shortest-lived vertebrates, whose lifespan ranges from three to nine months.This article includes expert inputs shared with TOI Health by:Dr Suchismitha Rajamanya, Lead Consultant & HOD - Internal Medicine, Aster Whitefield Hospitals.Inputs were used to explain how rare genetic variants identified in long-lived families may contribute to healthy ageing and why experts believe that a combination of inherited traits and lifelong lifestyle habits could help some people stay disease-free and active for years longer.