UW Medicine

Treatments to rejuvenate the aging heart?

Caloric restriction is an anti-aging strategy that has been shown to extend lifespan and improve age-related diseases in animal models including non-human primates. Rapamycin, an FDA approved immune-suppressant drug, shares some similar anti-aging effects as caloric restriction.  However, most studies of the anti-aging effects of caloric restriction or Rapamycin have been long-term studies in which the treatments were given for the majority of the subject’s lifespan.

Dr. Peter Rabinovitch, Professor of Pathology, and his lab set out to study the efficacy of short-term (10-week) treatment by either caloric restriction or Rapamycin on aged mice. Surprisingly, they discovered that not only was short-term treatment effective, but that both treatments substantially reversed the functional declines that were seen in the performance of aging hearts.

In the study, Altered proteome turnover and remodeling by short-term caloric restriction or rapamycin rejuvenate the aging heart, published in the journal Aging Cell on Feb 25, 2014, mice were given 10 weeks of treatment with either caloric restriction or Rapamycin. Both methods of treatment reversed the pre-existing age-dependent cardiac hypertrophy (enlarged heart) and diastolic dysfunction (decline in performance of one or both ventricles during diastole–the cardiac cycle phase during which the heart is relaxing and filling with incoming blood). Study of almost a thousand proteins by mass spectrometry (a method referred to as “proteomics”) showed that these improvements were accompanied by a reversal of age-related changes in multiple proteins involving energy metabolism, suggesting that both short-term caloric restriction and Rapamycin treatment make the protein pool in the old hearts more ‘young-looking’. This was confirmed by looking at the chemical metabolites involved in the pathways that produce energy in the heart.

The study also showed that after 10-weeks of caloric restriction or Rapamycin treatment, proteins in the hearts are recycled at a lower rate, meaning they stayed in the cells for longer time before they were broken down. Interestingly, despite staying in the cells for longer time, proteins in hearts of mice treated with caloric restriction or Rapamycin had less oxidative damage, suggesting that they are of better quality.

The ability of short-term caloric restriction or Rapamycin treatment to rejuvenate the aging heart highlights the potential of both treatments as therapeutic strategies for improving cardiac function in the elderly. As modern medicine has become more effective in treating hypertension and vascular disease, it has become increasingly apparent that there is also an intrinsic aging of the heart, even those without cardiovascular disease. This includes an increased prevalence of cardiac hypertrophy and diastolic dysfunction (sometimes called Heart Failure with Preserved Ejection Fraction, or HFPEF) due to aging.  These changes of the heart lead to exercise intolerance in the elderly, which contributes to frailty and further health complications. “The results of this study are particularly exciting, as potential treatments to rejuvenate the function of the aging human heart may be only 5-10 years down the road” says Dr. Rabinovitch.