The amassed scientific evidence of decades tells us that regular moderate exercise and the practice of calorie restriction with optimal nutrition are both very beneficial for long term health. There is no other presently available option that will result in a better expected outcome for the average basically healthy individual. That in turn suggests that we should be putting much more effort and attention into research that will generate better ways to extend the healthy span of life available to us. Exercise and calorie restriction are free, but speeding up longevity research requires organization, effort, and above all funding.
At present a great deal more research relating to exercise and calorie restriction takes place than that relating to means of extending life to a far greater degree. Rejuvenation biotechnology is the outcast poor cousin of the research community, for all that it is the best path forward towards radical life extension. That will have to change, but in the meanwhile here are a few recent examples of mainstream research, offered without comment, but similar to studies that come and go in volume month by month:
The clinical trial randomized 2,331 patients with heart failure and a left ventricular ejection fraction of less than or equal to 35 percent to either a formal exercise program plus optimal medical therapy, or to optimal medical therapy alone. Prior to randomization, patients underwent symptom-limited cardiopulmonary exercise tests to assess exercise capacity, as measured by peak oxygen uptake (VO2). Patients randomized to the exercise treatment arm participated in supervised walking, or stationary cycling for 30 minutes three days a week for six weeks. After completing 18 sessions, patients added 40 minutes of home-based exercise two days per week. After completing 36 supervised sessions, patients were fully transitioned to a five day per week, 40 minutes a day home-based exercise program.
The primary outcome of this analysis was a composite of all-cause mortality or hospitalization, stratified by gender. Women randomized to exercise training saw a 26 percent reduction in risk of all-cause mortality or hospitalization compared with a 10 percent reduction in risk of these outcomes for men randomized to exercise.
PICALM, BIN1, CLU, and APOE are top candidate genes for Alzheimer's disease, and they influence episodic memory performance in old age. Physical activity, however, has been shown to protect against age-related decline and counteract genetic influences on cognition. The aims of this study were to assess whether (a) a genetic risk constellation of PICALM, BIN1, and CLU polymorphisms influences cognitive performance in old age; and (b) if physical activity moderates this effect.
Data from the SNAC-K population-based study were used, including 2,480 individuals (age range = 60 to 100 years) free of dementia at baseline and at 3- to 6-year follow-ups. Tasks assessing episodic memory, perceptual speed, knowledge, and verbal fluency were administered. Physical activity was measured using self-reports. Individuals who had engaged in frequent health- or fitness-enhancing activities within the past year were compared with those who were inactive. High genetic risk was associated with reduced episodic memory performance, controlling for age, education, vascular risk factors, chronic diseases, activities of daily living, and APOE gene status. Critically, physical activity attenuated the effects of genetic risk on episodic memory. Our findings suggest that participants with high genetic risk who maintain a physically active lifestyle show selective benefits in episodic memory performance.
Although dietary restriction (DR) is known to extend lifespan across species, from yeast to mammals, the signalling events downstream of food/nutrient perception are not well understood. In Caenorhabditis elegans, DR is typically attained either by using the eat-2 mutants that have reduced pharyngeal pumping leading to lower food intake or by feeding diluted bacterial food to the worms. In this study, we show that knocking down a mammalian MEKK3-like kinase gene, mekk-3 in C. elegans, initiates a process similar to DR without compromising food intake.
This DR-like state results in upregulation of beta-oxidation genes through the nuclear hormone receptor NHR-49, a HNF-4 homolog, resulting in depletion of stored fat. This metabolic shift leads to low levels of reactive oxygen species (ROS), potent oxidizing agents that damage macromolecules. Increased beta-oxidation, in turn, induces the phase I and II xenobiotic detoxification genes, through PHA-4/FOXA, NHR-8 and aryl hydrocarbon receptor AHR-1, possibly to purge lipophilic endotoxins generated during fatty acid catabolism.
The coupling of a metabolic shift with endotoxin detoxification results in extreme longevity following mekk-3 knock-down. Thus, MEKK-3 may function as an important nutrient sensor and signalling component within the organism that controls metabolism. Knocking down mekk-3 may signal an imminent nutrient crisis that results in initiation of a DR-like state, even when food is plentiful.
While many studies have focused on the detrimental effects of advanced maternal age and harmful prenatal environments on progeny, little is known about the role of beneficial non-Mendelian maternal inheritance on aging. Here, we report the effects of maternal age and maternal caloric restriction (CR) on the life span and health span of offspring for a clonal culture of the monogonont rotifer Brachionus manjavacas.
Mothers on regimens of chronic CR (CCR) or intermittent fasting (IF) had increased life span compared with mothers fed ad libitum (AL). With increasing maternal age, life span and fecundity of female offspring of AL-fed mothers decreased significantly and life span of male offspring was unchanged, whereas body size of both male and female offspring increased. Maternal CR partially rescued these effects, increasing the mean life span of AL-fed female offspring but not male offspring and increasing the fecundity of AL-fed female offspring compared with offspring of mothers of the same age. Both maternal CR regimens decreased male offspring body size, but only maternal IF decreased body size of female offspring, whereas maternal CCR caused a slight increase.