A combination of 5-aminolevulinic acid hydrochloride and sodium ferrous citrate slowed age-associated muscular and mitochondrial decline in fruit flies.
In 2019, the number of people aged 60 years and older had reached 1 billion. By 2030, this number will rise to 1.4 billion and 2.1 billion by 2050. As the rate of global ageing is expected to accelerate in the coming decades, age-related disorders and diseases are also expected to increase. Of the various problematic features of ageing, frailty is a common syndrome characterised by increased vulnerability to disease and mortality due to physiological decline. Notably, frailty is linked to decreased muscle mass, reduced grip strength, and shorter and slower gait, all of which may increase susceptibility to falls and injury. However, there is a limited array of therapeutic interventions available to treat frailty and other age-related conditions.
In a recent study by scientists at Tokyo Metropolitan University, they have demonstrated that a mixture of 5-aminolevulinic acid (5-ALA) hydrochloride and sodium ferrous citrate (SFC) can help to delay ageing-related muscular deterioration in fruit flies, effectively slowing down locomotor decline and extending lifespans. The researchers have also found that these improvements were linked to better maintenance of muscle architecture and mitochondrial function.
While decreased mitochondrial function has long been recognised as a key contributing factor in ageing-related muscle decline, the precise mechanisms by which ageing affects the mitochondria have remained elusive. However, studies over the past decade have found that a combination of two chemicals – 5-ALA and SFC – appears to slow down mitochondrial decay in cultured cells. 5-ALA is known to be the starting point of the porphyrin cycle, which is important for producing heme, a precursor compound to the oxygen-carrying haemoglobin.
With this in mind, the researchers, led by Associate Professor Kanae Ando, believed that 5-ALA/SFC could potentially be used as a therapeutic to slow down age-related muscular decline. To test this hypothesis, the researchers incorporated 5-ALA/SFC into the food fed to Drosophila fruit flies and examined how their muscular health was affected. Their experiment revealed that the flies fed with the 5-ALA/SFC mixture experienced less decline in locomotor function over time and had longer lifespans.
To explain these findings, the team analysed the flies’ muscles under a microscope and found that the architecture of the individual myofibers that make up muscle tissues in older flies resembled those found in younger flies. They had a higher density of myonuclei in the centre of each fibre. Furthermore, when the scientists examined how this affected mitochondrial function, they made a surprising discovery. The addition of the chemicals did not appear to directly affect the activity or dynamics of the mitochondria, but rather the electric potential across the membrane that physically surround the mitochondria. This electric potential is directly linked to the production of reactive oxidative species (ROS), which can harm muscle tissue.
As the first study of its kind in organisms, their findings have not only uncovered a crucial mechanism that underlies the onset of ageing and frailty but also identified a potential therapeutic treatment that can mitigate age-related muscle decline and extend healthspan. Since 5-ALA phosphate/SFC is a common dietary health supplement, the team believes that it is well-suited to combat age-associated conditions that are generally caused by cumulative damage over time. [APBN]
Source: Nozawa et al. (2021). 5-Aminolevulinic acid and sodium ferrous citrate ameliorate muscle aging and extend healthspan in Drosophila. FEBS Open Bio, 12(1), 295-305.