Validation of anti-aging drugs by treating age-related diseases

Humans die from age-related diseases, which are deadly manifestations of the aging process. In order to extend life span, an anti-aging drug must delay age-related diseases. All together age-related diseases are the best biomarker of aging. Once a drug is used for treatment of any one chronic disease, its effect against other diseases (atherosclerosis, cancer, prostate enlargement, osteoporosis, insulin resistance, Alzheimer's and Parkinson's diseases, age-related macular degeneration) may be evaluated in the same group of patients. If the group is large, then the anti-aging effect could be validated in a couple of years. Startlingly, retrospective analysis of clinical and preclinical data reveals four potential anti-aging modalities

Cell cycle arrest is not yet senescence, which is not just cell cycle arrest: terminology for TOR-driven aging

Cell cycle arrest is not yet senescence. When the cell cycle is arrested, an inappropriate growth-promotion converts an arrest into senescence (geroconversion). By inhibiting the growth-promoting mTOR pathway, rapamycin decelerates geroconversion of the arrested cells. And as a striking example, while causing arrest, p53 may decelerate or suppress geroconversion (in some conditions). Here I discuss the meaning of geroconversion and also the terms gerogenes, gerossuppressors, gerosuppressants, gerogenic pathways, gero-promoters, hyperfunction and feedback resistance, regenerative potential, hypertrophy and secondary atrophy, pro-gerogenic and gerogenic cells

Progeria, rapamycin and normal aging: recent breakthrough

A recent discovery that rapamycin suppresses a pro-senescent phenotype in progeric cells not only suggests a non-toxic therapy for progeria but also implies its similarity with normal aging. For one, rapamycin is also known to suppress aging of regular human cells. Here I discuss four potential scenarios, comparing progeria with both normal and accelerated aging. This reveals further indications of rapamycin both for accelerated aging in obese and for progeria

Hormesis does not make sense except in the light of TOR-driven aging

Weak stresses (including weak oxidative stress, cytostatic agents, heat shock, hypoxia, calorie restriction) may extend lifespan. Known as hormesis, this is the most controversial notion in gerontology. For one, it is believed that aging is caused by accumulation of molecular damage. If so, hormetic stresses (by causing damage) must shorten lifespan. To solve the paradox, it was suggested that, by activating repair, hormetic stresses eventually decrease damage. Similarly, Baron Munchausen escaped from a swamp by pulling himself up by his own hair. Instead, I discuss that aging is not caused by accumulation of molecular damage. Although molecular damage accumulates, organisms do not live long enough to age from this accumulation. Instead, aging is driven by overactivated signal-transduction pathways including the TOR (Target of Rapamycin) pathway. A diverse group of hormetic conditions can be divided into two groups. “Hormesis A” inhibits the TOR pathway. “Hormesis B” increases aging-tolerance, defined as the ability to survive catastrophic complications of aging. Hormesis A includes calorie restriction, resveratrol, rapamycin, p53-inducing agents and, in part, physical exercise, heat shock and hypoxia. Hormesis B includes ischemic preconditioning and, in part, physical exercise, heat shock, hypoxia and medical interventions

NCI's provocative questions on cancer: some answers to ignite discussion

National Cancer Institute has announced 24 provocative questions on cancer. Here I try to answer some of them by linking the dots of existing knowledge

Why men age faster but reproduce longer than women: mTOR and evolutionary perspectives

Women live longer than men. Yet, it is believed that men do not age faster than women but simply are weaker at every age. In contrast, I discuss that men age faster. From evolutionary perspective, high accidental death rate in young males is compatible with fast aging. Mechanistically, hyper-activated mTOR (Target of Rapamycin) may render young males robust at the cost of accelerated aging. But if women age slower, why then is it women who have menopause? Some believe that menopause is programmed and purposeful (grandmother theory). In contrast, I discuss how menopause is not programmed but rather is an aimless continuation of the same program that initially starts reproduction at puberty. This quasi-program causes over-activation of female reproductive system, which is very vulnerable to over-activation. Mechanisms of aging and menopause are discussed

Molecular damage in cancer: an argument for mTOR-driven aging

Despite common belief, accumulation of molecular damage does not play a key role in aging. Still, cancer (an age-related disease) is initiated by molecular damage. Cancer and aging share a lot in common including the activation of the TOR pathway. But the role of molecular damage distinguishes cancer and aging. Furthermore, an analysis of the role of both damage and aging in cancer argues against “a decline, caused by accumulation of molecular damage” as a cause of aging. I also discuss how random molecular damage, via rounds of multiplication and selection, brings about non-random hallmarks of cancer