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Table 2. A summary of current FDA-approved pharmacotherapies for obesity
Name of drug Mechanism(s) of action Limitations
Phentermine Activates the sympathetic nervous system to promote Hypertension, insomnia, constipation, dry mouth, valvular heart
release of norepinephrine, dopamine and serotonin, disease, withdrawal effects, risk of abuse and dependence,
suppressing appetite and increasing the breakdown of approved for short-term use only, cannot use with history of
[145]
stored fat for energy CVD, indicated as a monotherapy
Diethylpropion Suppresses appetite and increases satiety by promoting Hypertension, insomnia, constipation, dry mouth, valvular heart
high levels of catecholamines, dopamine and disease, abuse potential, epilepsy, approved for short-term use
norepinephrine [144] only, cannot use with history of CVD, indicated as a
monotherapy
[145]
Orlistat Decreases GI absorption of fat Fatty/oily stool, fecal urgency, increased defecation, fecal
incontinence, reduced absorption of fat-soluble vitamins
Phentermine- Stimulates the sympathetic nervous system and inhibits Numbness, dizziness, dry mouth, constipation, altered taste
topiramate fatty acid synthesis [145] perception, insomnia, anxiety
Bupropion- Increases dopamine and norepinephrine levels to suppress Nausea and vomiting, constipation, headache, dizziness,
[145]
naltrexone appetite and food intake insomnia, dry mouth
[145]
Liraglutide GLP-1 receptor agonist ; Increases satiety and delays Nausea and vomiting, abdominal pain, increased heart rate,
gastric emptying thyroid cancer risk, hypoglycemia, infections
Gelesis-100 Superabsorbent hydrogel particles of a cellulose-citric acid Abdominal distension, infrequent bowel movements, indigestion
matrix that increases volume and firmness of meals [146]
Semaglutide GLP-1 receptor agonist [145] ; Reduces food cravings and Nausea and vomiting, diarrhea, constipation, risk of hepatobiliary
energy intake and gallbladder disorders, increased heart rate
FDA: Food and Drug Administration; CVD: cardiovascular disease; GLP-1: glucagon-like peptide-1; GI: gastrointestinal.

O (Foxo), and insulin-like growth factor (IGF). Senolytic agents are another class of anti-aging therapies,
which kill senescent cells to reduce cellular senescence. Many currently approved FDA drugs target
mechanisms underlying aging, although they are indicated for other diseases. Most notably, the antidiabetic
[150]
drug metformin has been proposed to be a promising anti-aging candidate . A systematic analysis
revealed the association between metformin and decreased all-cause mortality and suggested the drug may
[151]
also extend lifespan . Other evidence shows increased autophagy and improved mitochondrial function
following treatment with metformin, ameliorating age-associated inflammation. Other FDA-approved
drugs also hold promise as novel anti-aging candidates, although limited by adverse side effects [Table 3].

TARGETING THE GUT MICROBIOTA WITH BIOTICS TO IMPROVE OBESITY AND AGING
The limitations of current pharmacotherapies necessitate the development of novel therapeutics for obesity
and aging. Targeting the gut using biotics to manipulate the microbiome and GI environment is an
attractive option to restore microbial homeostasis and host health. Biotics represent material derived from
living, or once living, organisms and can exist in many forms, namely prebiotics, probiotics, synbiotics, and
postbiotics. Simply, prebiotics are food components that benefit the gut microbiota, while probiotics are live
microorganisms that elicit benefits to the host and synbiotics are the synergistic combination of probiotics
[162]
and prebiotics . The newest biotic form, postbiotics, represents substances released or produced by
microbiota metabolism that benefit the gut microbiota and the host. Many biotics exert beneficial properties
for human health that may improve obesity and promote healthy aging.

Prebiotics
Intake of dietary fiber plays a beneficial role in gut health. Prebiotics are non-digestible fermented dietary
[163]
fibers that selectively stimulate the growth of beneficial probiotics to improve host health . The
degradation of prebiotics by the gut microbiota allows beneficial microbes to obtain survival energy and
release fermentation products such as SCFAs and other metabolites that influence a variety of metabolic
effectors [164,165] . There are several types of prebiotics, including fructans and oligosaccharides, which naturally
occur in dietary food products such as berries, asparagus, garlic, onion, chicory, honey, and wheat, among