In addition to its tranquil high quality and a way of peace, the recent, crisp, pollutant-free mountain air may assist some animals live longer.
Specifically, the decrease oxygen content material at excessive altitudes will increase lifespan considerably in ageing mice, in accordance with a examine revealed in PLOS Biology on May 23, 2023.
Why examine hypoxia?
The researchers have famous that theirs is the primary examine to show that oxygen restriction, or steady hypoxia, can prolong lifespan in an ageing mammal. Previous experiences on oxygen restriction lengthening lifespan have come from mammalian cells grown in Petri dishes, yeast, and in less complicated lab animals corresponding to roundworms and fruit flies.
This line of analysis has been attention-grabbing, no less than in half, by the bare mole rat: a rodent that spends most of its life in an oxygen-deficient burrow with a lifespan for much longer than scientists have been in a position to predict primarily based on its dimension or evolutionary historical past.
“Because of several observations about the effects of hypoxia in other organisms, we were motivated to assess the effect of chronic continuous hypoxia in a mammalian ageing model,” Vamsi Mootha, a researcher on the Howard Hughes Medical Institute, Maryland, and professor at Harvard Medical School, whose workforce made the invention, informed The Hindu.
What was the examine design?
For its experiments, the workforce labored with a pressure of mutant mice that age prematurely and have a shorter lifespan, of fewer than six months. “Wild type mice (without the mutations causing a shortened lifespan) can live over three years, which would have been a very long first experiment to assess survival, so we chose a mouse model of accelerated ageing,” stated Dr. Mootha.
The strains they used “also responds powerfully to the best-known intervention to extend lifespan across organisms – caloric restriction.” Caloric restriction, or dietary restriction with out malnutrition, first described in 1935, is the gold-standard for rising lifespan in various species like yeast, roundworms, fruit flies, mice, and rats.
To check the impact of low oxygen stage on these mice, the researchers housed them in hypoxic chambers with an oxygen focus of 11%, much like that on the base camp of Mt. Everest. They achieved hypoxic situations by diluting the air with nitrogen.
The median lifespan of mice residing with regular oxygen – at 21% of the environment, a.ok.a. normoxia – was about 16 weeks. But mice residing in hypoxic situations had a median lifespan of 24 weeks, or 50% longer.
“We were pleasantly surprised by the results,” Dr. Mootha stated. “We have long been excited by the possibility that hypoxia could be beneficial in an ageing model and wanted to rigorously test this hypothesis, but we had no assumptions that it would actually have a significant effect.”
The animals housed in hypoxic situations additionally displayed higher neurologic operate than their counterparts residing in normoxic situations. Sixteen-week-old mice residing in normoxia had neurologic debility, measured by a motor efficiency check, whereas mice maintained in hypoxic situations carried out the check considerably higher.
How does hypoxia work?
Next, the researchers tried to grasp how hypoxia affected the physique, resulting in longer lifespan, however with little success. They examined whether or not hypoxia prompted the mice to limit their diets. But they discovered that the hypoxic mice ate barely extra meals than these residing in normoxia, ruling out dietary restriction as the elemental underlying mechanism.
Looking for in a different way expressed genes, DNA injury restore, and adjustments in signalling pathways didn’t present any definitive clues both.
“There are many open questions at this point,” Dr. Mootha stated. “At present we don’t know the mechanism by which hypoxia extends lifespan in these mice and it remains to be seen whether these findings would generalise to wildtype mice with a three-year lifespan. Much more research is required here.”
Is the examine important?
“This paper is one in a fabulous series of interesting papers from the Mootha lab,” Arvind Ramanathan, affiliate professor at Bengaluru’s Institute for Stem Cell Science and Regenerative Medicine, whose work contains metabolic regulation of tissues throughout mammalian ageing, informed The Hindu. “The mechanism by which hypoxia leads to increased lifespan is unclear.”
Parminder Singh, a researcher of ageing on the Buck Institute for Research on Aging, California, stated, “The study provides valuable insights into the potential of hypoxia to enhance healthy lifespan. The findings open up new avenues for exploring the mechanisms underlying hypoxia’s impact on lifespan and hold promise for potential interventions in the future.”
But he, like Dr. Ramanathan as nicely, stated extra analysis is required.
“Ageing is a highly complex phenomenon, involving numerous molecular mediators,” Dr. Ramanathan stated. Hypoxia might not goal many facets of ageing because it doesn’t have an effect on the expression of a gene (p21) that’s an essential marker of ageing, he added. “Moving to areas with lesser oxygen is quite premature and may even be unwise under certain underlying disease contexts.”
Do the findings apply to people?
Dr. Singh agreed: “Caution should be exercised in directly translating these findings to human populations, as more work is required to establish their applicability and to address limitations, including variations in species, environmental conditions, and broader health outcomes.”
“It’s very premature to extrapolate our findings to humans or to make any recommendations for human health based on our current findings,” Dr. Mootha additionally stated. “To my knowledge, there is no evidence that people living at high altitude have a longer maximal lifespan, but there are some clues that median lifespan might be increased at higher altitude, and the most interesting epidemiological clue about the human health effects of living at altitude is actually provided by modern Indian history.”
He was referring to a examine revealed in 1977, in which physicians of the Indian Army in contrast the well being outcomes of 1.3 lakh troopers stationed on plains and their 20,000 comrades stationed at 3,700-5,600 metres above sea stage, over three years. They discovered that the incidence of widespread age-related problems like diabetes, hypertension, and coronary heart illness was decrease amongst troopers on the excessive altitudes than these at sea stage.
Dr. Mootha stated much more work is required to grasp the impact of hypoxia on ageing in individuals and the molecular mechanisms by means of which it may be useful. “We view this initial report as laying the foundation for this important line of future research.”
Sneha Khedkar is a biologist-turned freelance science journalist primarily based out of Bengaluru.
