The beneficial effects of calorie restriction on health and longevity are well researched in mammals, but while a sizable fraction of those benefits are thought to be mediated via sensing of amounts of specific proteins such as methionine and cysteine, there is comparatively little investigation of protein restriction strategies - usually meaning a reduced dietary intake of one or more proteins, while overall calorie intake remains at the same level. Work in this part of the field is taking place, and shows extension of life span to some degree in rodent studies, but it has a long way to go to catch up to the breadth of research into calorie restriction.
Calorie restriction is, of course, not yet decisively proven to slow aging extend life in humans, through the existing data makes a strong argument for this to be the case. It isn't expected to have much more than a five year effect on human life span, however. While the short term benefits of calorie restriction are similar in different mammalian species, the measured effects on longevity scale down with species life span. The reasons for this to be the case remain to be determined.
While specific aspects of the biochemistry of the calorie restriction response are quite well investigated, such as its effects on autophagy, there is enormous complexity in the way in which all of the changes fit together with the details of metabolism to determine the pace of aging. Meaningful progress towards a full map of the biochemistry and progression of aging still lies ahead - and will likely still be an ongoing project well after rejuvenation therapies based on the SENS model of damage repair are a going concern.
In this open access review, the authors argue that there is enough evidence at the present time to expect protein restriction strategies such as methionine restriction to produce benefits in our species. We should be looking at protein restriction in much the same way as we look at exercise and calorie restriction: a reliable, demonstrated way to slightly slow the aging process and obtain benefits to long term health, a method just one step short of the final decisive proof and calibration of the size of the effect.
Amino acids are the building blocks of all proteins in the body. A subcategory called sulfur amino acids includes methionine (Met) and cysteine (Cys), which not only make up proteins but also play many roles in metabolism and health. Researchers have been interested in dietary sulfur amino acid restriction since the 1990s, when studies began to show health benefits in animals fed Met-restricted diets. In one early study involving rats, 80 percent Met restriction increased average and maximum lifespans by between 42 and 44 percent.
Scientists have long known that animals on calorie-restricted diets live longer and healthier, but they've been searching for ways bring about the improvements without asking people to eat less. In new review of studies, sulfur amino acid restriction consistently demonstrated a range of beneficial effects including enhanced lifespan - without calorie restriction. The analysis found that Met restriction has been associated with delayed aging and longer lifespans in human cells, yeast, and animals including fruit flies and rodents. Animals fed sulfur amino acid-restricted diets also had health improvements including reductions in body weight, fat and oxidative stress; fewer cancerous tumors; enhanced insulin sensitivity; and more efficient fuel-burning.
"This review describes a number of studies which provide some hints that sulfur amino acid restriction might achieve some of the benefits observed in animal models, including cancer inhibition and reducing risks for cardiovascular disease." Researchers are now overseeing the first tightly controlled feeding study of dietary sulfur amino acid restriction in human subjects, which may provide more direct evidence of health benefits.
Sulfur amino acids (SAAs) play numerous critical roles in metabolism and overall health maintenance. Preclinical studies have demonstrated that SAA-restricted diets have many beneficial effects, including extending life span and preventing the development of a variety of diseases. Dietary sulfur amino acid restriction (SAAR) is characterized by chronic restrictions of methionine and cysteine but not calories and is associated with reductions in body weight, adiposity, and oxidative stress, and metabolic changes in adipose tissue and liver resulting in enhanced insulin sensitivity and energy expenditure. SAAR-induced changes in blood biomarkers include reductions in insulin, insulin-like growth factor-1, glucose, and leptin and increases in adiponectin and fibroblast growth factor 21.
On the basis of these preclinical data, SAAR may also have similar benefits in humans. While little is known of the translational significance of SAAR, its potential feasibility in humans is supported by findings of its effectiveness in rodents, even when initiated in adult animals. To date, there have been no controlled feeding studies of SAAR in humans; however, there have been numerous relevant epidemiologic and disease-based clinical investigations reported. Here, we summarize observations from these clinical investigations to provide insight into the potential effectiveness of SAAR for humans.