The FDA doesn't categorize aging as a disease, so there is no mechanism to get approval for an anti-aging drug. Maybe it's time for change.
The Scheibye-Knudsen lab has analyzed 1.5 billion prescriptions from 4.8 million individuals over 40 years in The Danish National Health Service Prescription Database and correlated this with the survival of individuals prescribed certain drugs.
The lab has identified 3 drugs for non-aging conditions that could be repurposed for aging. Aubrey de Grey, who is one of the world’s leading – and most talked-about – biomedical gerontologists, is frequently quoted:
The first people who will live to 1,000 are already breathing.
He's not crazy. The pace of gerontology research is accelerating. Universities and research labs all over the world are working on various aspects.
The National Institute of Health (NIH) even has research grants. But a quick look at their grants reveals the problem: The grants are for diseases/conditions that affect older people, like Alzheimer's. None are for creating a healthy older life. As the NIH says:
Many factors influence healthy aging. Some of these, such as genetics, are not in our control. Others — like exercise, a healthy diet, going to the doctor regularly, and taking care of our mental health — are within our reach.
But even inside the NIH, things are starting to change. Richard Hodes is director of the National Institute on Aging, one of the 27 Institutes under NIH. He states the changing focus:
The goal is to improve not simply life span but what is now referred to as health span: a high quality of life throughout life.
It's about time (pun intended). It does no good to live longer if it's just to hang on longer in a rest home or hospital bed.
Today, we better understand that for almost every cell and organelle, there is a system of information integration and signaling output, in addition to the cell autonomous effects that were found previously. These signals may arise in response to cues that anticipate future needs, particularly to tune reproduction to available nutrients or to coordinate responses to stresses on an organism-wide basis.
These signals weren't on the scientific radar a couple of decades ago. Things are changing fast. Current research is divided into physical, mental and social issues of growing old.
Physical
All brains age, but some age faster. PubMed identified an area that is undergoing massive research:
With this review, we explore and summarize evidence that the dynamics of gut-resident bacteria can modulate molecular brain function and contribute to age-related neurodegenerative disorders.
Who would have thought that what was in our digestive tract would have an influence on aging and health?
DNA damage associated with short telomeres is first observed in the gut; it is concomitant with reduced cell proliferation, accumulation of senescent cells and functional defects both in naturally aging and tert−/− zebrafish. Importantly, telomere shortening results in cellular and functional defects in the gut at a time when other organs are clear of tissue dysfunction. As in zebrafish, the human gastrointestinal system is one of the organs with the fastest rate of telomere shortening.
Counteracting gut aging improves health of the entire organism, reverting gut microbiota dysbiosis and aging phenotypes in distant organs of tert−/− zebrafish.
Zebrafish aren't humans, so a lot more work needs to be done, but the suspicion that the health of the gut has an effect on overall health is more than a century old.
Another physical cause of aging is inflammation -- in this case reduced mitochondrial uptake of calcium.
Our findings pinpoint the mitochondrial calcium uniporter complex as a keystone molecular apparatus that links age-related changes in mitochondrial physiology to systemic macrophage-mediated age-associated inflammation.
In this case changes in mitochondrial physiology leads to inflammation, which is a known cause of premature aging. In mice experimenters were able to increase the uptake of calcium with a corresponding decrease in inflammation.
Mental
Until recently, there was no help for Alzheimer disease (AD) patients. There are several therapies that slow down the symptoms, but still nothing that shuts down AD. However, there is hope:
A modification in tau conformation results in toxic aggregation. Therefore, the prevention of tau aggregation becomes an interesting approach for drug discovery to reduce AD progression. Studies in mice have shown that tau oligomers cause mitochondrial damage, disruption of neuronal signaling, synaptic loss, and memory impairment. Disease-modifying therapeutics (DMT) like small molecules can be used to inhibit the initial step in the tau aggregation and thereby reduce its accumulation.
A much better inhibitor, but still a slower of symptoms, not a reduction in damage. Two-thirds of the AD victims are women. Researchers are starting to look at sex-specific causes and treatments. As the Journal of Neuroinflammation, from the NIH says:
Inflammatory gene signatures associated with AD are enriched in microglia from post-menopausal women.
This is going to get researchers to revisit failed AD treatments that didn't account for the variation between sexes. Several trials failed -- and they didn't separate results for men and women. AD is different for women, so a lot of research comes back into play.
Back in the 1960s research was done on several hallucinogens. Research was generally positive, but the field of hallucinogens was abandoned due to legal restrictions. Lately, hallucinogens have made a comeback, promising therapeutics for alcohol and tobacco addiction, depression and more.
Although promising early phase research conducted from the 1950s through the early 1970s was discontinued before firm conclusions could be reached concerning the efficacy of any of the classic hallucinogens for any clinical condition, the research that was conducted in that era strongly suggests that classic hallucinogens have clinically relevant effects, particularly in the case of LSD treatment of alcoholism. In the past decade, clinical trials have resumed investigating the effects of classic hallucinogens in the treatment of existential distress in the face of cancer, and in the treatment of addictions including alcoholism and nicotine addiction.
Researchers are starting to work on a number of areas that hallucinogens might prove effective.
Accumulated research to date suggests psychedelic drug assisted psychotherapy may emerge as a potential breakthrough treatment for several types of mental illnesses including depression, anxiety, post-traumatic stress disorder, and addiction that are refractory to current evidenced based therapies.
This is not an exhaustive list. It may be that PTSD, depression and anxiety are not one condition and that halucinogens would be the therapeutic for some of the variations and not others. In trials, where they have worked they have been effective. Researchers just need to find the specific use cases. They don't appear to work for everyone.
Social
As the World Health Organization (WHO) says:
High-quality social connections are essential to our mental and physical health and our well-being. Social isolation and loneliness are important, yet neglected, social determinants of the health of older people.
In the US, there isn't much effort to deal with old age.
Ageism is defined as discrimination against older people because of negative and inaccurate stereotypes—and it’s so ingrained in our culture that we often don’t even notice. Most organizations now have diversity, equity, and inclusion (DEI) departments to tackle issues such as racism and gender bias. Even in those departments, age bias is seldom on the radar. “Ageism is this odd ‘-ism’ in that it’s still socially acceptable in many ways,” said Joann Montepare, PhD, director of the RoseMary B. Fuss Center for Research on Aging and Intergenerational Studies at Lasell University in Newton, Massachusetts, and past president of APA’s Division 20 (Adult Development and Aging).
Social connections tend to contract as people get older. Deaths and friends moving to places for retirement disrupt lifelong patterns. These social contacts are not generally replaced as they are for younger, working people.
But one of the biggest markers for a successful older life is contacts. Without contacts people become depressed and die early. Association with younger people is necessary, yet modern society tends to move the elderly "out of the way".
Conclusion
As the Public Library of Science (PLOS) says:
A third shift is the translational focus of the longevity field, from an almost entirely academic endeavor to one that is being taken up by industry and clinics—that is, the findings we have made in academic labs are on the verge of becoming actual aging treatments.
As the field transitions to companies and away from institutions, there will be investment opportunities. Just make them fairly small. There's always a new treatment entering trials.
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