Secrets of ageing, longer lifespan revealed in breakthrough researches

*Studies identify learning, staying in shape, key proteins found in worms, mammals

People who are overweight cut their life expectancy by two months for every extra kilogramme of weight they carry, research suggests.A major study of the genes that underpin longevity has also found that education leads to a longer life, with almost a year added for each year spent studying beyond school.

Other key findings are that people who give up smoking, study for longer and are open to new experiences might expect to live longer.
Scientists at the University of Edinburgh, United Kingdom (U.K.), analysed genetic information from more than 600,000 people alongside records of their parents’ lifespan.

Because people share half of their genetic information with each of their parents, the team were able to calculate the impact of various genes on life expectancy.Lifestyle choices are influenced to a certain extent by our Deoxy ribonucleic Acid (DNA)/genetic material/genes, for example, have been linked to increased alcohol consumption and addiction. The researchers were therefore able to work out which have the greatest influence on lifespan.

Their method was designed to rule out the chances that any observed associations could be caused by a separate, linked factor. This enabled them to pinpoint exactly which lifestyle factors cause people to live longer, or shorter, lives.

They found that cigarette smoking and traits associated with lung cancer had the greatest impact on shortening lifespan.For example, smoking a packet of cigarettes per day over a lifetime knocks an average of seven years off life expectancy, they calculated. But smokers who give up can eventually expect to live as long as somebody who has never smoked.

Body fat and other factors linked to diabetes also have a negative influence on life expectancy.The study also identified two new DNA differences that affect lifespan. The first — in a gene that affects blood cholesterol levels — reduces lifespan by around eight months. The second — in a gene linked to the immune system — adds around half a year to life expectancy.

The research, published in Nature Communications, was funded by the Medical Research Council.Data was drawn from 25 separate population studies from Europe, Australia and North America, including the UK Biobank — a major study into the role of genetics and lifestyle in health and disease.

Professor Jim Wilson, of the University of Edinburgh’s Usher Institute, said: “The power of big data and genetics allow us to compare the effect of different behaviours and diseases in terms of months and years of life lost or gained, and to distinguish between mere association and causal effect.”

Dr. Peter Joshi, Chancellor’s Fellow at the University of Edinburgh’s Usher Institute, said: “Our study has estimated the causal effect of lifestyle choices. We found that, on average, smoking a pack a day reduces lifespan by seven years, whilst losing one kilogram of weight will increase your lifespan by two months.”

Also, a new molecular pathway that controls lifespan and health in worms and mammals has been identified by researchers.The researchers showed that microscopic worms with excess levels of these proteins live longer and healthier than normal worms.They also showed that mice with excess levels of these proteins demonstrated a delay in blood vessel dysfunction associated with ageing.

The study has major implications for the understanding of ageing and age-associated disorders such as heart disease and dementia. Researchers found that a family of proteins called KLF’s decrease with age, and sustained levels of KLFs can prevent the age-associated loss of blood vessel function.

KLF proteins work by controlling autophagy – a recycling process that cells use to clear debris such as misfolded proteins or normal molecular byproducts that build up in old age.

According to the researchers, the loss of this ‘quality control’ mechanism is a hallmark sign of ageing.The study, conducted by researchers at Case Western Reserve University School of Medicine and University Hospitals Health System, involved experiments where the proteins in question were artificially increased or decreased.

“We find that by artificially increasing or decreasing the levels of a family of proteins called Kruppel-like transcription factors (KLF), we can actually get these small worms (Caenorhabditis elegans) to live for longer or shorter time periods,” said first author Nelson Hsieh, MD/PhD fellow at Case Western Reserve University School of Medicine.

“Since this same family of proteins also exists in mammals, what is really exciting is that our data suggests the KLFs also have similar effects on ageing in mammals, too.”The researchers found that KLF levels decrease with age, and that sustained levels of KLFs can prevent the age-associated loss of blood vessel function.

When the researchers conducted further analyses, they found that KLF proteins work by controlling autophagy – a recycling process that cells use to clear debris such as misfolded proteins or normal molecular byproducts that build up in old age.

According to the researchers, the loss of this ‘quality control’ mechanism is a hallmark sign of ageing.“As cells age, their ability to perform these functions declines,” the authors wrote in their study.“This likely leads to an unsustainable accumulation of toxic protein aggregates, which ultimately present an obstacle to cellular survival.”

Indeed, worms without KLF proteins cannot maintain the autophagy process and die early.According to the researchers, the next step of the research will be to study the precise mechanisms underlying how autophagy in cells lining blood vessel contributes to improved blood vessel function.

“As our population ages, we need to understand what happens to our heart and arteries, as we rely on them to function perfectly later and later on in our lives,” said Hsieh. “Our findings illuminate what can happen during aging, and provide a foundation to designing interventions which slow these processes.”