Applied Healthspan engineering

Abstract

According to the Homeric Hymn to Aphrodite, when Eos asked Zeus for Tithonus to be granted immortality, she forgot to ask for eternal youth. Applied Healthspan Engineering (AHE) seeks to address this problem. All organisms have a minimal level of functional reserve required to sustain life that eventually declines to a point incompatible with survival at death. AHE seeks to maintain or restore optimal functional reserve of critical tissues and organs. Tissue reserve correlates with well being. Diet, physical exercise, and currently available small-molecule-based therapeutics may attenuate the rate of decline of specific organs or organ systems, but are unlikely to restore lost reserve. Inherent evolutionary-derived limitations in tissue homeostasis and cell maintenance necessitate the development of therapies to enhance regenerative processes and possibly replace whole organs or tissues. AHE supports the study of cell, tissue, and organ homeostatic mechanisms to derive new regenerative and tissue replacement therapies to extend the period of human health.

FIG. 1.

Minimal goal of Applied Healthspan Engineering (AHE) is to square the healthspan curve. Well-being peaks at the end of growth phase and then declines. AHE seeks to stabilize well-being, possibly resulting in increased longevity. Strategies for Engineered Negligible Senescence (SENS) seeks to increase longevity by "defeating" aging.

FIG. 2.

Cardiac reserve limits longevity. Heart rate (left) as well as total number of heartbeats per lifetime (right) as well as heart rate correlate with life expectancy in mammals. (Figure modified from ref. 9).

FIG. 3.

Schematic depiction of decline in functional reserve with aging. Tissue reserve (illustrated by boxed area) decreases with age. Environmental stressors can push an individual (or an organ system) outside of the box. Therapy such as penicillin can restore well-being to a patient suffering from a life-threatening bacterial infection (inside the box).

FIG. 4.

Pulmonary reserve (forced expiratory volume, 1 s [FEV1]) declines with age (upper); however, decline can be slowed by statin therapy (lower). (Top) FEV, a measure of pulmonary function, decreases with age. (Based on data from ref. 20). (Bottom) Statin use slows decline in FEV in 803 men with an average age of 71. Forced vital capacity (FVC) and FEV1 were measured two to four times between 1995 and 2005. (Figure modified from ref. 25).

FIG 5.

Renin–angiotensin system physiology. AI/AII, Angiotensin I and II; ADH, antidiuretic hormone; ACE, angiotensin-converting enzyme.